Sexual Differentiation in Early Development PDF

SEXUAL DIFFERENTIATION EARLY IN DEVELOPMENT  DIFFERENCES BETWEEN AN OVUM AND A SPERM Male sperms: They are produced in large numbers. However, producing large numbers of cells is costly for the body. Therefore, the body cuts down the size of the sperms. The energy cost o...

SEXUAL DIFFERENTIATION EARLY IN DEVELOPMENT  DIFFERENCES BETWEEN AN OVUM AND A SPERM Male sperms: They are produced in large numbers. However, producing large numbers of cells is costly for the body. Therefore, the body cuts down the size of the sperms. The energy cost of sperm production is cheap for the male body. Female eggs: They are produced in small amounts. They are much larger than the sperms. The energy cost of ovum production is expensive.  EVOLUTIONARY PSYCHOLOGY OF HUMAN MATE CHOICE Evolutionary psychologists argue that: Males aim to inseminate as many females as possible. Males are indiscriminate (careless) in mate selection. Males do not need to be choosy (picky) in mate preference. Because, they produce many sperms which they can waste with wrong mates.  Females aim to maximize offspring survival: They are very choosy (picky) in mate selection! Females choose the male that holds the food, territory (area) or the nest-site that they need to reproduce. Therefore, this male must be strong and healthy. Females choose the males with sexually attractive traits which signal a healthy genetic background. Hence, the offsprings of the most choosy female will have a better chance to survive and reproduce.  Autosomes Sex chromosomes determine our sex: X and Y chromosomes Males have one X and one Y chromosome: XY Females have two X chromosomes: XX A sperm may contain either one X or one Y chromosome. An ovum contains only one X chromosome. If a sperm carrying an X chromosome fertilizes an ovum carrying an X chromosome, the offspring will be a female (XX). If a sperm carrying a Y chromosome fertilizes an ovum carrying an X chromosome, the offspring will be a male (XY). Presence or absence of Y chromosome determines sex in mammals. In a vertebrate embrio, genital organs develop from three primitive structures: A primitive gonad (primitive testes or ovaries) Two sets of ducts: Wolffian and Müllerian ducts A genital tubercle Male embrio: There is a special region on Y chromosome called SRY (sex-determining region on Y chromosome) gene. SRY gene in the primitive gonad synthesizes SRY protein. Female embrio: There is no SRY gene. No SRY protein is produced. 7 – 8th WEEK OF GESTATION Male embrio: SRY protein causes the cells in the core of primitive gonads to proliferate → gonads develop into testes. Female embrio: No SRY protein → cells in the outer layers of primitive gonads proliferate → gonads develop into ovaries. Therefore, presence or absence of Y chromosome (SRY gene) determines whether the primitive gonads will develop into testes or ovaries. 7 – 8th WEEK OF GESTATION Following gonadal development, the remaining genital organs develop. Development of these genital organs depends on the presence of testosterone! 15th WEEK OF GESTATION Male embriyo: Testes synthesize testosterone and anti- müllerian hormone (AMH). Testosterone leads to the development of Wolffian ducts into internal genital organs: Epididymis, vas deferens, seminal vesicles, prostate and bulbourethral gland. AMH causes the müllerian ducts to shrink.  15th WEEK OF GESTATION Testosterone is converted to a more potent androgen, dihydrotestosterone (DHT) in some peripheral tissues. DHT is responsible for the development of external genital organs: Genital skin is differentiated into scrotum. Genital tubercle is differentiated into penis.  15th WEEK OF GESTATION In female embrio: Ovaries produce NO SEX HORMONE! In female embrio, absence of testosterone: Leads to the development of Müllerian ducts into internal genital organs: fallopian tubes, uterus and inner vagina. Leads to the development of external genital organs: Causes the genital tubercle to develop into clitoris. Causes genital skin to develop into labia minora, labia majora and outer vagina.  POSTNATAL PERIOD (AFTER BIRTH) During the first three months after birth, sex hormone secretion is high. However, this secretion decreases progressively during the following months. Sex hormone production declines until a minimum level is reached. This period lasts until puberty. Şekil erkeklere ait; ancak doğum sonrasındaki durum kadınlar için benzer!  ACTIONS OF ANDROGENS (TESTOSTERONE, DHT) During puberty and adulthood: Androgens stimulate spermatogenesis and maturation of all male genital organs: Primary male sexual characteristics! Androgens are also responsible for the development of the secondary male sex characteristics in men: Deepening of the voice, male body shape, male- pattern of hair growth, loss of scalp hair, increased oil production in the skin, acne Anabolic effects: Androgens increase protein synthesis especially in the skeletal muscle and bones. This action accelerates muscle development and increases linear body growth (body length). Testosterone affects the brain to regulate male reproductive behavior, sex drive (libido) and aggresive behavior.  ACTIONS OF ESTROGENS During puberty and adulthood: Estrogens stimulate the maturation of female genital organs leading to the development of primary sex characters. Trigger the development of secondary sex charaters in females: Formation of female body shape, breast development Anabolic actions: Estrogens increase protein synthesis especially in the bones. This action increases linear body growth (body length). Estrogens increase the contractility of smooth muscle cells in the uterus. In males and adult females, estrogens regulate reproductive behavior by acting on the brain. REGULATORY ROLE OF GONADAL SEX HORMONES IN RODENT BRAIN AND SEXUAL BEHAVIOR  GENERAL EFFECTS OF GONADAL SEX HORMONES ACTIVATIONAL EFFECT: An effect which disappears when the hormone is absent and triggered when the hormone is present. Temporary effects of hormones that "come and go" with the presence and absence of the hormone.  GENERAL EFFECTS OF GONADAL SEX HORMONES ORGANIZATIONAL EFFECT: It is a permanent alteration of the body and nervous system, and thus permanent change in behavior. It results from the action of sex hormones early in the development. These organizational effects take place during a critical (sensitive) period of development. The most important critical periods are during fetal development and a short period after birth. When this critical period is over, organizational effect does not disappear even if the hormone is removed from the body. During early development, sex hormones permanently organize both the reproductive and nervous systems. In adulthood, sex hormones activate the reproductive and nervous systems leading to reproductive behaviors.  DHT T T T DHT (fetal testes) Androgen E T receptor E Estrogen receptor MASCULINIZATION OF BEHAVIOR IN MALES When testosterone reaches the brain, it shows activational and organizational effects by inducing 3 different signaling pathways in the neurons: 1.Testosterone (T) → androgen receptors → masculinization of behavior 2.Testosterone is converted to dihydrotestosterone (DHT) → androgen receptors → masculinization of behavior (male type sexual behavior, aggresive behvior)  MASCULINIZATION OF BEHAVIOR IN MALES 3. Testosterone is converted to estradiol → estrogen receptors → masculinization and defeminization of behavior. Defeminization: Prevention of the development of female characteristics such as suppression of lordosis!  ACTIVATIONAL EFFECTS OF GONADAL HORMONES IN MALE SEXUAL BEHAVIOR Testosterone: Increases the male’s interest in the female. Increases mounting frequency and duration. Is essential for successful ejaculation. When an adult male rat is castrated (removal of gonads) → he will stop ejaculating and mounting. If a castrated adult male is treated with testosterone → reproductive behaviors are restored. These are the activational effects of testosterone. In normal development, the rise of androgen secretion at puberty activates masculine behavior in males. A small amount of testosterone is enough to fully maintain the mating behavior in male rats. Blood levels of testosterone are not responsible for different levels of sexual vigor. ORGANIZATIONAL EFFECTS OF GONADAL HORMONES IN MALE SEXUAL BEHAVIOR 1. When adult male rats are treated with estradiol + progesterone, they never show lordosis behavior (Figure A). This experiment shows that when testosterone is present during development, it suppresses lordosis permenantly : Defeminization, organizational effect Lordosis cannot be activated in adult male rats even if they are treated with female sex hormones. 2. When newborn male rats are first castrated and then exposed to testosterone in adulthood → they do not show mounting behavior! This experiment shows that testosterone shows an organizational effect on mounting behavior (masculinization). When testosterone is absent during development, it will not show an organizational effect on mounting behavior.  Tested with Tested with male receptive female On the other hand, When newborn male rats are castrated and treated with estradiol + progesterone during adulthood → they display lordosis! Why? Castration during development prevented the defeminization effect (suppression of lordosis) of testosterone; the activational effect of estradiol + progesterone triggered lordosis behavior. CONCLUSION: In males, androgens are required both during development (organizational effect) and adulthood (activational effect) to fully masculinize both the body and behavior!  ACTIVATIONAL EFFECTS OF GONADAL HORMONES IN FEMALE SEXUAL BEHAVIOR Sequential release of estrogen and progesterone increases: 1.Proceptive behaviors during proestrus. 2.Receptive behavior (lordosis) in response to male mounting during estrus. If an adult female rat is castrated → she will show neither proceptive nor receptive behavior. Adult female is castrated → 2 days of estrogen treatment followed by a single injection of progesterone → proceptive and receptive behaviors are restored (activational effect). ORGANIZATIONAL EFFECTS OF GONADAL HORMONES IN FEMALE SEXUAL BEHAVIOR  Tested with Tested with male receptive female Birth Adult Sensitive Period 1. Absence of testosterone during sensitive period and presence of estrogen and progesterone during adulthood permits lordosis behavior in females (Figure B). Testosterone injections to female rats during intrauterine life → female rats do not show lordosis even if they receive estradiol + progesterone treatment in adulthood (Figure C). This experiment shows that the presence of androgens during development suppresses lordosis permanently (organizational effect). 2. Testosterone injections to female rats during intrauterine life and neonatal period (organizational effect) → testosterone injections during adulthood (activational effect) → female rats show mounting! (Figure C) This experiment shows that, in female rats, presence of testosterone during development and adulthood fully masculinized the behavior!  ORGANIZATIONAL EFFECTS OF GONADAL HORMONES IN FEMALE AND MALE SEXUAL BEHAVIOR 3. Absence of estrogen during sensitive period permits lordosis behavior in females! Newborn female rats are treated with estrogen → they fail to show lordosis! When estrogen is applied during development, it defeminizes the brain. Newborn female rats are treated with estrogen and then during adulthood treated with testosterone → they display mounting! These observations show that estrogenic hormones defeminize and masculinize the rodent brain. During normal development of male rodent brain, testosterone enters the brain and converted to estrogens which defeminize and masculinize the brain. ORGANIZATIONAL EFFECTS OF GONADAL HORMONES IN FEMALE AND MALE SEXUAL BEHAVIOR On the other hand, the absence of androgens during development (organizational effect) and the presence of estradiol + progesterone during adulthood (activational effect) feminize both the body and the brain. Classical view suggests that, during sensitive period, female sex hormones do not contribute to the development of female genital organs and female brain. Female brain develops independently of estradiol! REGULATORY ROLE OF GONADAL HORMONES IN HUMAN SEXUAL BEHAVIOR EFFECTS OF GONADAL HORMONES IN SEXUAL BEHAVIOR OF MEN When adult men are castrated: Testosterone is decreased to very low levels. Libido is decreased dramatically. Strength and duration of erections are reduced. Ejeculation and orgasm are reduced. Spermatogenesis is decreased; this leads to infertility. Body hair decreases. Body strength and muscle mass decrease. There may be gynecomastia (swollen breast tissue) These are activational effects of androgens in men. Similar effects are observed in men during andropause. Andropause usually develops in men older than 60. Testosterone synthesis in testes is reduced during andropause → blood testosterone levels are very low. EFFECTS OF GONADAL HORMONES IN SEXUAL BEHAVIOR OF WOMEN In women, estrogens increase sexual behavior by an activational effect. However, progesterone is suggested to inhibit sexual behavior. Several observations support the activational effect of estrogens on sexual behavior: 1. Ovaries stop synthesizing estrogens during menopause (45 - 55 years of age). Menopause leads to decreased levels of estrogens in blood. Some of the postmenopausal women report reduced libido. 2. Libido may decrease also in castrated women. 3. Libido varies during the menstrual cycle, and the frequency of female sexual activity increases when estrogen levels are maximum. On the other hand, libido tend to decrease when progesterone levels are high. EFFECTS OF GONADAL HORMONES IN SEXUAL BEHAVIOR OF WOMEN Interestingly, androgens also increase libido and sexual behavior in women! During postmenopausal stage, androgens are more effective in increasing the female libido. Therefore, androgens, rather than estrogens, are prescribed in postmenopausal women to increase libido. Estrogens are prescribed to increase vaginal lubrication in postmenopausal women.  What determines a person’s sexual orientation? 1. The sociocultural influences that instruct developing children about how they should behave when they grow up. 2. Sex chromosomes and genetic background. 3. Differences in the fetal exposure to sex hormones that could organize the developing brain to be attracted to females or males in adulthood.  HOMOSEXUALITY IN MEN AND WOMEN Homosexuality is sexual attraction, or sexual behavior between members of the same sex/gender («Gay» for males, «Lesbian» for females). Plasma concentrations of sex steroids are perfectly “normal” (typical of the gonadal sex) in both gay men and lesbians. One of the hypothesis which explains homosexuality in females states that: Exposure to sex hormones (testosterone or estradiol) during development (intrauterine and neonatal life) masculinizes the female brain. One of the hypothesis which explains homosexuality in males states that: Insensitivity to or lack of androgens during development (intrauterine and neonatal life) feminizes the male brain. DISORDERS OF SEXUAL DEVELOPMENT CONGENITAL ADRENAL HYPERPLASIA (CAH) Congenital: present from birth Adrenal gland synthesizes excess amounts of the weak androgens, which are converted to testosterone and DHT in adipose tissue. XX individuals have an intersex appearance: phallus (undifferentiated tissue which will form the penis or clitoris) is intermediate in size between a normal clitoris and a normal penis, skin folds resemble both labia and scrotum: Ambiguous genitalia appearance. In severe cases, penis and scrotum are well formed: Fully masculinized! They may be raised as boys. There are ovaries (fallopian tubes and uterus) instead of testes. Puberty: Male-pattern of hair growth, deepening of the voice, aggressive behavior. Fully masculinized XX individuals report satisfactory sexual intercourse with females Most of them are heterosexual. However, as females with CAH grow older, the percentage of homosexuality increases to as much as 40%. ANDROGEN INSENSITIVITY The XY individual has a dysfunctional SYNDROME androgen receptor gene which is incapable of producing normal androgen receptor. These individuals have testes which synthesize testosterone and AMH. However, there is no response to the androgens: Wolffian ducts fail to develop; no epididymis, vas deferens, seminal vesicles, prostate, bulbourethral gland. AMH suppresses the development of müllerian ducts: No fallopian tubes and uterus, they have shallow vagina, external tissues form labia and clitoris. They are infertile. They look like other females at birth. They develop breasts at puberty. They behave like other women. They display female sexual behavior. 5α-REDUCTASE DEFICIENCY: Prevalent in Turkey, Dominican Republic and Papua New Guinea. Due to a genetic mutation, XY individual cannot produce the enzyme (5α-reductase) which converts testosteron to DHT. DHT is not synthesized in these patients. These individuals have testes and the other male internal genital organs. However, male external genitalia fail to develop: Ambiguous genitalia appearance. They are born with a micropenis which looks like an enlarged clitoris: They are raised as females. At puberty, testosterone production increases: penis and scrotum enlarge, secondary male characteristics develop. Although these patients are raised as females, some choose to be males and some choose to be females during adolescence. REPRODUCTIVE BEHAVIOR IN ANIMALS  Stages of Reproductive Behavior: 1. Sexual attraction 2. Appetitive behavior 3. Copulation (coitus) 4. Postcopulatory behavior  SEXUAL ATTRACTION It is the first step in mating behavior of many animals. Animals emit (release) stimuli that attract members of the opposite sex. In many species, females are attracted to males that display the best species-typical ornaments (accesories) or traits (characteristics). These traits are usually related to the appearance of the individual.  SEXUAL ATTRACTION However, female or male animals may be attracted also to the movements, voice or smell of the opposite sex. These traits may signal healthy genetic background that make the individual desirable as a mate. These traits are regulated by sex hormones! Attraction is measured by observing the responses of potential mates: How rapidly they approach to the mate? How hard they work to gain access to the mate?  SEXUAL ATTRACTION IN FEMALES Sexual attraction between sexes is greatest when the female is in proestrus! Proestrus is characterized by high estrogen levels. High estrogen levels in females lead to the development of attractive traits. Most male mammals are attracted by particular female odors (pheromones) which are regulated by estrogens.  Females may find a particular male to be unattractive and refuse to mate with him. If the animals are attracted to each other, they may progress to the next stage: «Appetitive Behavior».  APPETITIVE BEHAVIOR Appetitive behaviors are actions that bring animals in contact with a mate. They are species-specific behaviors. They establish, maintain, or promote (advance) sexual interaction. During proestrus, a female displaying appetitive behaviors is said to be proceptive. Proceptive female rats exhibit «ear wiggling», and a hopping and darting (run rapidly) gait. Male appetitive behaviors consist of staying near the female, sniffing around the female’s face and vagina.  COPULATION (COITUS, INTROMISSION) If both animals display appetitive behaviors, they may progress to the third stage of reproduction: «Copulation». Copulation: In mammals, male inserts his penis into the female’s vagina. When stimulation reaches a threshold level, male ejaculates the sperm-containing semen into the vagina. Ejaculation: Discharge of semen from the male reproductory tract. The aim of copulation and ejeculation is bringing the sperm and egg together. COPULATION IN RATS AND MICE Male posture during copulation: Mounting Male mounts the female from the rear and grasps her flanks (side of the body between ribs and hips) with his forelegs. Female posture during copulation: Lordosis Lordosis: Female rat elevates the rump (buttocks) and moves the tail to one side, allowing copulation.  If a female is willing to copulate, she is said to be sexually receptive. Female mammals are receptive when they are in estrus (heat). In most species, females determine if a copulation will take place or not. A female may be proceptive and not receptive: Females are receptive only during estrus. Sequential increases in estrogen (red arrow) and progesterone (blue arrow) during proestrus permits lordosis during estrus. POSTCOPULATORY BEHAVIORS After copulation, a refractory period occurs. 1. Sexual attraction and appetitive behaviors are suppressed during this period. Animals will not mate again until refractory period has elapsed. The refractory period varies from minutes to months depending on the species. Many animals will resume mating sooner, if they are provided with a new partner: Coolidge effect. POSTCOPULATORY BEHAVIORS 2. Parental behaviors: For mammals and birds, postcopulatory behavior includes parental behaviors to nurture the offspring → nest- building behaviors etc. 3. Pair bonding: In some species such as voles and birds, the male and female form long- lasting social and sexual pair bonds; they live together after mating. NEURAL CIRCUITS REGULATING REPRODUCTIVE BEHAVIOR IN THE RODENT BRAIN  Most of what we know about the neural circuitry of sexual behavior comes from studies of rodents. In the rodent brain, odors and pheromones trigger olfactory circuits. Olfactory information is transmitted first to the medial amygdala and then to the hypothalamus. NEURAL CIRCUITS FOR REPRODUCTION IN FEMALE RAT  In female rats, ventromedial hypothalamus (VMH) is the key brain region which regulates lordosis. VMH neurons express high levels of estrogen and progesterone receptors.  During proestrus, near estrous, the sequential increase in estrogen and progesterone secretion permits lordosis behavior in estrus. Sequential binding of estrogens and progesterone to their receptors in the VMH leads to lordosis! When the secretion of both hormones decreases, lordosis is inhibited.  Spinal motor neurons VMH neurons send axons to the periaquaductal gray (PAG) region in the midbrain (mesencephalon). PAG neurons project to the medullary reticular formation, which in turn projects to the spinal cord via reticulospinal tract. Axons in the reticulospinal tract activate spinal motor neurons in the lumbar spinal cord to activate back muscles producing lordosis. NEURAL CIRCUITS FOR REPRODUCTION IN MALE RAT  In male rats, hypothalamic medial preoptic area (mPOA) is the key brain region which regulates mounting behavior. mPOA neurons express androgen receptors. Binding of testosterone to androgen receptors in the mPOA leads to mounting!  mPOA neurons also contain estrogen receptors! In the male brain, testosterone is converted to estradiol and dihydrotestosterone (DHT). Estradiol binds to the estrogen receptors and DHT binds to the androgen receptors in the mPOA to promote sexual behavior in male rat. In male rodents, the activity of estrogen receptor–containing neurons in the VMH is responsible for whether a male mouse attacks or mounts another mouse.  Spinal motor neurons mPOA sends axons to the ventral midbrain. Ventral midbrain sends axons to 2 brain regions: 1. Basal Ganglia: This brain region regulates mounting. 2. Brainstem nuclei (paragigantocellular nucleus): Brainstem nuclei send axons to the lumbar and sacral spinal cord motor neurons to regulate erection and ejeculation. ANATOMY OF THE REPRODUCTIVE ORGANS IN HUMAN  MALE REPRODUCTIVE SYSTEM External genital organs: Penis Scrotum: It contains the testes. Internal genital organs: Testes (testicles): Male gonads Epididymis Ductus deferens Ejaculatory duct → It opens into the urethra. Glands: Seminal vesicles, prostate, bulbourethral glands  STRUCTURE OF THE TESTES Testes contain the seminiferous tubules. The walls of the seminiferous tubules contain spermatogenic cells: They develop into spermatozoa (sperm cell) This process is called spermatogenesis: Sperm synthesis Spermatogenesis process takes about 64 – 74 days. 128 million sperms are produced each day!  STRUCTURE OF THE TESTES TESTIS Leydig cells are found between the seminiferous tubules; they synthesize testosterone. Testosterone is a strong stimulator of spermatogenesis.  FEMALE REPRODUCTIVE SYSTEM External genital organs (vulva): Internal genital organs: Mons pubis Vagina Labia majora, labia minora Uterus Clitoris Fallopian tubes (uterine tubes) Uretheral opening (meatus) Ovaries: Female gonads Vaginal opening (introitus)  OVARİES Ovum (egg) is found in the follicles. At birth, ovaries contain about 1 million follicles. By the time a girl enters puberty, this number declines to 300,000. Each follicle consists of an ovum (egg) surrounded by follicular cells called granulosa and theca cells. Granulosa and theca cells synthesize estradiol and progesterone.  MENSTRUAL CYCLE When puberty is reached, each month, women go through cyclic (regularly repeated) hormonal changes, which is called the menstrual cycle. These changes are observed in sex hormone (estradiol and progesterone) secretion. The mean duration of a menstrual cycle is 28 days. The length of the most cycles varies between 25 to 30 days. The length of a menstrual cycle is determined by the number of days from the first day of menstrual bleeding to the onset of next menses. First day of mens: Full, red flow, not spotting!  Follicular phase Luteal phase Ovulation Follicle rupture MENSTRUAL CYCLE The first two weeks are called the follicular phase and the last two weeks are called the luteal phase. Ovulation: Follicle ruptures to release the egg; it takes place approximately on day 14. Blood estrogen levels increase twice during the menstrual cycle. First rise occurs during the mid-follicular phase, which is followed by a second rise during the mid-luteal phase. On the other hand, blood progesterone levels increase only during luteal phase. HUMAN SEXUAL BEHAVIOR  HUMAN SEXUAL RESPONSE CYCLE CONSİSTS OF 4 PHASES: Clitoral erection Penile erection 1. EXCITEMENT: In general, activity in the sympathetic nerves terminating in the heart and blood vessels increases → heart rate increases, blood vessel walls constrict (vasoconstriction) and blood pressure increases. Breathing is accelerated. On the other hand, activity in the parasympathetic nerves innervating the blood vessels in the penis, clitoris, labia and vagina increases. This leads to the widening of blood vessels (vasodilation) → blood flow in the penis and clitoris increases → in women, clitoris and labia minora swell (clitoral erection); in men, penis swells (penile erection). Vaginal secretions increase. Muscles surrounding the outer one-third of vagina constricts. 2. PLATEAU: Excitement reaches a plateau. Physical changes initiated in phase 1 are intensified. 3. ORGASM: Brief and extremely pleasurable sensations are experienced by both sexes. Pelvic floor muscles contract. In men, muscles of vas deferens, seminal vesicle and prostate and the muscles located at the base of penis contract and propel semen through urethra. This process is called ejaculation; it occurs under sympathetic control! In women, muscles of uterus and vagina contract. Blood pressure, heart rate, and breathing are at their highest rates. 4. RESOLUTION: Excitement decreases. Erection subsides. The body slowly returns to its normal level of functioning. Swelled and erect body parts return to their previous size and color.  Differences in the sexual response patterns of men and women: 1. Most men have only one basic sexual response pattern. The typical male pattern includes a refractory period following orgasm. Refractory period: Men cannot achieve full erection and another orgasm until some time has elapsed; the length of time varies from minutes to hours. 2. Women have at least 3 typical sexual response patterns. Most women do not have a refractory period.  Motor performance and sexual drive are two different processes. They are regulated by two different neural pathways. Motor performance is the sexual act, itself; it is regulated by neural pathways discussed in the previous lecture. Sexual drive = sexual motivation = libido: It is regulated by the reward system in the brain. Both are under the control of sex hormones. Impotence: Being unable to achieve the motor performance (erection or ejaculation). In most of the impotence cases, only the motor performance is affected without any loss of libido. However, sometimes decreased libido accompanies motor dysfunction.  FERTILIZATION Fertilization: Fusion of sperm and ovum (egg). Zygote: When sperm and ovum fuse, they form the zygote. Zygote divides multiple times to become the embrio → development of fetus  DIFFERENCES BETWEEN AN OVUM AND A SPERM Male sperms: They are produced in large numbers. However, producing large numbers of cells is costly for the body. Therefore, the body cuts down the size of the sperms. The energy cost of sperm production is cheap for the male body. Female eggs: They are produced in small amounts. They are much larger than the sperms. The energy cost of ovum production is expensive.  EVOLUTIONARY PSYCHOLOGY OF HUMAN MATE CHOICE Evolutionary psychologists argue that males: They aim to inseminate as many females as possible. They are indiscriminate (careless) in mate selection. Males do not need to be choosy (picky) in mate preference. Because, they produce many sperms which they can waste with wrong mates. Females: They aim to maximize offspring survival: They are very choosy (picky) in mate selection! Females choose the male that holds the food, territory (area) or the nest-site that they need to reproduce. Therefore, this male must be strong and healthy. Females choose the males with sexually attractive traits which signal a healthy genetic background. Hence, the offsprings of the most choosy female will have a better chance to survive and reproduce. SLEEP  SLEEP Recommended sleep durations according to the National Sleep Foundation in USA: Infants (up to 1 year): 12-15 hours Preshoolers (up to 5 years): 10-13 hours School aged children (5-12 years): 9-11 hours Teenagers (adolescents, 13-18 years): 8-10 hours Young adults (18-21 years) and adults: 7-9 hours Older adults: 7-8 hours  STAGES OF SLEEP Non-REM (NREM) Sleep – Stage 1 – Stage 2 – Stage 3 REM Sleep (Rapid Eye Movement)  A sleep cycle is the progression through the various stages of NREM sleep to REM sleep. During the early part of the night: Stage 1 → 2 → 3 → 2 → REM (one cycle) Following REM, there may be a brief awakening (frequently changing position in the bed). If there is no awakening, REM is usually followed by stage 2. An adult goes through 4 to 6 sleep cycles during a typical night.  The first cycle is about 70-100 minutes long. The following cycles are about 90-120 minutes long. Cycles early in the night are characterized by greater amounts of stage 3 sleep. The latter half of the night has less stage 3 sleep; sometimes there is no stage 3. In contrast, the first REM period in the first cycle is the shortest, lasting only 5- 10 minutes. REM sleep gets longer throughout the night. The last REM period just before waking may last up to 45-60 minutes. In young adults: 75-80% of sleep is non-REM sleep. The longest sleep stage during a typical night is non-REM stage 2. 45-50% of sleep is stage 2 sleep. REM sleep accounts for about 20-25% of total sleep.  CHARACTERISTIC EEG PATTERNS DURING DIFFERENT STAGES OF SLEEP Different stages of sleep are classified according to the EEG patterns.  NON-REM STAGE 1 Early portion of stage 1 sleep produces alpha waves (8 - 13 Hz). As the individual continues through stage 1 sleep, there is an increase in the theta activity. Stage 1 is characterized by the presence of theta waves (4 - 7 Hz) and vertex spikes (sharp waves with high amplitude). This stage usually lasts several minutes.  NON-REM STAGE 2 Theta waves dominate the activity. Stage 2 is defined by the presence of sleep spindles and K complexes. Sleep spindles: Low amplitude waves with very high frquency K complexes: Waves with high amplitude.  NON-REM STAGE 3 Stage 3 is defined by the appearance of delta waves (0.5 - 4 Hz, up to 100 μV). As this stage progresses, delta waves dominate the EEG activity: High amplitude, low frequency waves; slow wave sleep! Synchronized activity of sleep: A large number of pyramidal neurons display synchronized, low frequency electrical activity → this produces high amplitude delta waves in the EEG  REM SLEEP EEG recordings display a pattern of small-amplitude, high frequency activity, which is similar to the pattern of an awake individual: Beta, alpha and theta waves. However, the individual is still sleeping: Paradoxical sleep Desynchronized activity of sleep → Number of pyramidal neurons which display simultaneous electrical activity decreases, frequency of the electric activity increases; this results in low amplitude, high frequency waves. PHYSIOLOGICAL CHANGES DURING DIFFERENT STAGES OF SLEEP  Non-REM STAGE 3 [SLOW WAVE SLEEP (SWS), DEEP SLEEP] When compared to wakefulness: The activity of the sympathetic nervous system decreases to minimum levels. The activity of the parasympathetic nervous system increases. Metabolic rate, body temperature, respiration, heart rate and blood pressure decline to their lowest levels. Respiration and heart rate is slow and regular. Cerebral blood flow is reduced.  Non-REM STAGE 3 [SLOW WAVE SLEEP (SWS), DEEP SLEEP] Tonus in skeletal muscles is reduced: Hypotonia However, some tonus is still present and some motor behavior is still possible. Under the closed eyelids, eyes roll slowly. Sensory threshold is increased; it is very hard to wake someone up from stage 3. Growth hormone secretion is increased during deep sleep.  REM SLEEP (RAPID EYE MOVEMENT, PARADOXICAL SLEEP) When compared to non-REM: The activity of the sympathetic nervous system increases. Metabolic rate, body temperature, respiration, blood pressure and heart beat increase to near waking levels. Respiration and heart beat is irregular with high bursts. Sensory threshold decreases; it is easier to wake someone up from REM. Cerebral blood flow is increased.  REM SLEEP (RAPID EYE MOVEMENT, PARADOXICAL SLEEP) Atony and complete relaxation develops in skeletal muscles. Your arm and leg muscles become temporarily paralyzed: This prevents you from acting out your dreams. REM sleep behavior disorder! Only, the diaphragm and the extraocular muscles contract: Diaphragm contraction produces inspiration. Extraocular muscle contraction produces rapid eye movements (REM). Increased parasympathetic activity continues and elicits (induces) penile erection, clitoral enlargement and pupillary miosis (constriction of the pupils).  SLEEP PATTERNS CHANGE WITH AGE REM sleep and non-REM stage 3 sleep decreases with age! When you get old, the number of awakenings increases. DREAMS Most of your dreaming occurs during REM sleep. Some dreaming can ocur also in non-REM stage 2. non-REM dreams are of a more «thinking» type: Simple ideas REM dreams are vivid and involve sensory perceptions such as sights, sounds, smell etc. Generally, REM dreams which occur during the first half of the night are more realistic and are a reflection of our daily experiences. REM dreams which occur during the second half of the night are more fantastic, unreal, odd or involve intense emotions.  BIOLOGICAL FUNCTIONS OF SLEEP 1. Body restoration: Materials such as proteins which are used during the waking hours are rebuild during sleep. 2. Energy conservation: Motor behavior, metabolic rate, heart contractions, respiration are suppressed during sleep; we use less energy (ATP) and conserve ATP when we sleep. 3. Memory consolidation: We cannot acquire new information during sleep! However, sleep helps us to consolidate information that is acquired while awake! Both REM and non-REM sleep are proposed to have important roles in the consolidation of memories. Consolidation: Converting short-term memories into long-term ones. The decline in stage 3 sleep with age may be related to diminished cognitive capabilities!  METABOLITE ACCUMULATION UNDERLIES SWS During wakefulness, metabolites accumulate in the brain and generate a homeostatic sleep response. An important example is adenosine: Metabolite of ATP hydrolysis (break down) Adenosine binds adenosine receptors and inhibits wake-promoting neurons located in the RAS, hypothalamus, basal forebrain and cerebral cortex. Caffein and theophylline in coffee and tea are psychostimulants: They act as antagonist ligands of adenosine receptors.  NEURAL PATHWAYS WHICH LEAD TO SWS (ENDOGENOUS SWS SYSTEM) The activity of neurons which synthesize the inhibitory neurotransmitter GABA increases in two brain regions: 1. Basal forebrain 2. Ventrolateral preoptic nucleus (VLPO) in the hypothalamus GABA binds to GABAA receptors, which are ligand-gated Cl- (chloride) channels. The axons from basal forebrain and VLPO reach and inhibit wake-promoting nuclei in the RAS, hypothalamus, basal forebrain and cerebral cortex. Noradrenergic neuron activity in the LC decreases. Serotoninergic neuron activity in the raphe nuclei decreases. Cholinergic neuron activity in the PPT and LDT decreases to minimal levels.  General anesthetics bind GABAA receptors causing them to open more easily. They induce SWS-like state by activating the endogenous SWS system.  NEURAL PATHWAYS UNDERLYING REM SLEEP 1. The activity of the cholinergic neurons in LDT and PPT nuclei increases prominently to induce REM sleep. 2. Cholinergic neurons activate a pathway that inhibits the NA neurons in LC and serotonin neurons in raphe. Activity of NA and serotonin neurons decreases to minimal levels so that wakefulness is suppressed!  SLEEP HYGIENE 1. Wake up at the same time every day. 2. Go to bed when you are feeling sleepy. 3. Ensure your body is getting enough sun light. 4. Bed and pillows should be comfortable. 5. Establish a regular relaxing bedtime routine: Warm shower, reading a book, light stretches 6. Exercise regularly; avoid strenuous workouts close to bedtime. 7. Limit daytime naps to 30 minutes; avoid naps especially in the afternoon. 7. Avoid heavy meals close to bedtime. 8. Avoid stimulants such as caffeine and nicotine close to bedtime. 9. Limit your intake of fluids two hours before bedtime. 10. Avoid blue light (computers, tablets, cell phones, TV) at night. TOPICS WHICH ARE INCLUDED IN THIS COURSE WAKEFULNESS and SLEEP REPRODUCTIVE BEHAVIOR EMOTIONS LEARNING and MEMORY PERCEPTION Mark Breedlove: Psychologist and neuroscientist Professor of Neuroscience in the Department of Psychology, Michigan State University, USA Neil. V. Watson: Psychologist and neuroscientist Professor of Neuroscience in the Department of Psychology, Simon Fraser University in Vancouver, Canada WAKEFULNESS Dr. Burcu Balkan  CONSCIOUSNESS It is the awareness of: The stimuli in the internal and external environment Our perceptions Our feelings Our thoughts  CONSCIOUSNESS Consciousness is the result of the activity in the specific neuron populations in the brainstem, hypothalamus and basal forebrain, which project diffusely over a wide area of the cerebral cortex. These projections determine our state of consciousness through the regulation of our cerebral activity.  CONSCIOUSNESS State of consciousness varies over the course of the day. There are multiple levels of consciousness: Waking consciousness: Being alert → being drowsy Sleep: nonREM, REM Coma  Sensory perception and consciousness are regulated by two different neural pathways. However, two pathways interact with each other: Sensory stimuli Consciousness Sensory stimuli regulate our consciousness level: Exposure to excessive sensory stimuli → Wakefulness! Lack of sensory stimuli → Drowsiness, sleep! Consciousness level regulates the sensitivity of the cerebral cortex to sensory stimuli: Wakefulness: Sensitivity to sensory stimuli increases Sleep, coma: Sensitivity to sensory stimuli decreases RETICULAR ACTIVATING SYSTEM (RAS)  RETICULAR ACTIVATING SYSTEM (RAS) It is a collection of various nuclei found in the reticular formation localized to the upper brainstem: Mesencephalon (midbrain) and pons. Neuron populations in the RAS regulate wakefulness, sleep and consciousness.  SENSORY PATHWAYS Neurons in the sensory pathways are specific to the modality of the sensory stimulus: They are unimodal! For example: Neurons in the visual pathway can be activated only with light. Sensory pathways (except the olfactory pathway) first project to the specific sensory relay nuclei in the thalamus. Then, neurons in each specific sensory relay nuclei in thalamus project to a specific primary cerebral cortex. Thalamus is the major source of sensory information to the primary sensory cortex for all of the senses except olfaction. RAS Neurons in the somatosensory, visual and auditory pathways send axonal projections to the neurons in the RAS → RAS is activated! Each neuron located in RAS receives sensory information from different sensory pathways! Neurons in the RAS are multi- modal: Respond to various stimulus modalities. Therefore, RAS is a non-specific neural pathway!  RAS NUCLEI WHICH REGULATE THE STATE OF CONSCIOUSNESS 1. Locus coeruleus (LC): Noradrenaline (NA) synthesizing neurons 2. Pedunculopontine (PPT) and laterodorsal tegmental (LDT) nuclei: Acetylcholine (ACh) synthesizing neurons 3. Raphe nuclei: Serotonin synthesizing neurons 4. Substantia nigra (SNc) and ventral tegmental area (VTA): Dopamine (DA) synthesizing neurons  NA’ergic neuron activity in LC: Max during wakefulness; decreases during nonREM sleep; stops during REM sleep. Serotonergic neuron activity in raphe nucleus: Increases during wakefulness; decreases during nonREM sleep; stops during REM sleep. Cholinergic neuron activity in PPT and LDT: Increases during wakefulness and REM sleep; min during nonREM sleep. Increased activity of the neurons in RAS nuclei leads to wakefulness!  OTHER BRAIN REGIONS WHICH REGULATE WAKEFULNESS 1. Hypothalamus: Tuberomammillary nucleus (TMN): Neurons which synthesize histamine Lateral hypothalamic area (LHA): Neurons which synthesize orexin, mutations in the orexin or orexin receptor genes leads to narcolepsy! 2. Basal forebrain: Neurons which synthesize ACh. The activity in these neuron populations is higher during wakefulness compared to sleep. Increased activity in these neurons leads to wakefulness.  Pathways originating from RAS, hypothalamus and basal forebrain reach and activate cerebral cortex diffusely: WAKEFULNESS! These pathways are called Acending Reticular Activating System (ARAS)! ARAS includes two pathways: 1. Dorsal pathway: It activates cerebral cortex through non-specific thalamic nuclei. 2. Ventral pathway: It by-passes thalamus and reaches cerebral cortex directly.  ARAS Diffuse projections to the Cerebral Cortex Basal Forebrain Thalamus Non-specific nuclei Hypothalamus RAS (PPT, LDT) RAS DORSAL PATHWAY VENTRAL PATHWAY REGULATION OF WAKEFULNESS  Sensory stimuli in the environment activate the specific sensory neurons. Axons of the sensory neurons give collaterals to the neurons in the RAS nuclei. These collaterals stimulate RAS at high frequency → ventral and dorsal ARAS pathways → diffuse activation of cerebral cortex → WAKEFULNESS!  Damage to RAS or ARAS leads to the loss of consciousness: Coma Therefore, damage to the spinal cord or brainstem areas below pons does not cause loss of consciousness. General anesthesia drugs and central nervous system depressants (ethanol, barbiturates, benzodiazepines) inhibit the activity of RAS and ARAS. Barbiturates and benzodiazepines (xanax, diazem, valium etc.) are used medically as anxiolytics, hypnotics and anticonvulsants. Central nervous system stimulants (amphetamine, cocaine, nicotine etc.) increase the activity of RAS and ARAS. CIRCADIAN RHYTHM  CIRCADIAN RHYTHMS The natural cycle of physical, mental, and behavior changes that the body goes through in a 24-hour cycle. A cycle is a series of events that happen in a particular order, one following the other, and are often repeated. In circadian rhythms, the cycles last ~24 hours. Most functions of living organisms display a rhythm of approximately 24 hours. From Latin, “circa” means “about,” and “dies” means “day”  CIRCADIAN RHYTHMS Which body functions are influenced by circadian rhythms? Sleep-wake cycles Physical activity (locomotor activity): Humans are active during daytime (diurnal). Most rodents are nocturnal—active during dark period! Melatonin levels: High during nighttime; max during sleep! Body temperature Secretion of hormones into the blood Blood pressure and heart rate Where is the endogenous clock that drives circadian rhythms? Circadian rhythms are mostly affected by light. A subregion of the hypothalamus—the suprachiasmatic nucleus (SCN), serves as the biological clock. In mammals, retinal ganglion cells in the retina inform the SCN when there is light in the environment.  Retinohypothalamic Pathway Certain retinal ganglion cells contain a photopigment, called melanopsin that makes them sensitive to light. Melanopsin is most sensitive to light frequencies in the blue range! These cells send their axons to synapse directly within the SCN: Retinohypothalamic pathway This pathway carries information about light to the hypothalamus.  Retinohypothalamic pathway RETINA SUPRACHIASMATIC NUCLEUS EFFERENT AXONS Pineal gland Brain regions which regulate sleep-wakefulness, locomotor activity, body temperature, autonomic nervous system and hormone secretion  PINEAL GLAND Neural connections from the SCN to the pineal gland regulate melatonin secretion. The activity of the SCN sets up a circadian rhythm for melatonin release. Retinohypothalamic pathway enables light stimulus to inhibit melatonin secretion from the pineal gland. Therefore, melatonin secretion increases during darkness (nighttime). Melatonin secretion starts to increase at around 21:00 - 22:00 pm. Melatonin receptors are expressed both in the brain and in the body. Melatonin regulates circadian ryhthms such as sleep/wake cycle in the body. ELECTROENCEPHALOGRAPHY (EEG)  Electroencephalography (EEG) is a method to record electrical activity of the brain. EEG electrodes are placed along the scalp. It is used for the diagnosis of neurological disorders, especially seizure disorders such as epilepsy. EEG signal is considered as a sum of postsynaptic potentials, which are generated in the apical dendrites of the pyramidal neurons in the cerebral cortex. Postsynaptic potentials: Excitatory (EPSP) and inhibitory (IPSP) postsynaptic potentials  When electrical activity in thousands of pyramidal neurons occur simultaneously, they summate so that they can be recorded by EEG. When the number of pyramidal neurons that produce simultaneous electrical activity increases, the amplitude of the waves recorded by the EEG gets larger. This is called synchronization.  2 Hz There are 4 main waves in the EEG: Alpha, beta, theta and delta EEG waves have an amplitude and a frequency. As the consciousness level decreases, the amplitude of the waves increases, whereas the frequency decreases. As the consciousness level increases, the amplitude of the waves decreases, whereas the frequency increases. Alpha Beta Theta Delta Alpha waves (8-13 Hz, Synchronized activity of wakefulness): These waves appear when we close our eyes, relax and do not focus on a thought. They have a higher amplitude and lower frequency compared to beta waves. A large number of pyramidal neurons display synchronized electrical activity → this produces high amplitude-waves in the EEG. Alpha waves are prominent over parietal and occipital areas. Wave type Frequency Amplitude Delta 0.5 - 4 Hz Up to 100 μV Theta 4 - 7 Hz Alpha 8 - 13 Hz 20 - 40 μV Beta 13 - 30 Hz 10 - 30 μV  Wave type Frequency Amplitude Delta 0.5 - 4 Hz Up to 100 μV Theta 4 - 7 Hz Alpha 8 - 13 Hz 20 - 40 μV Beta 13 - 30 Hz 10 - 30 μV Beta waves (13-30 Hz, Desynchronized activity of wakefulness): These waves appear when there is sensory stimulation (eyes open), when we focus on a thought (increased attention) or when we are anxious. They have a lower amplitude and a higher frequency compared to alpha waves. Desynchronized activity → Number of pyramidal neurons which display simultaneous electrical activity decreases, frequency of the electric activity increases; this results in low amplitude, high frequency beta waves. Beta waves are prominent over frontal areas. Wave type Frequency Amplitude Delta 0.5 - 4 Hz Up to 100 μV Theta 4 - 7 Hz Alpha 8 - 13 Hz 20 - 40 μV Beta 13 - 30 Hz 10 - 30 μV Theta waves (4 - 7 Hz): They are observed in children and adolescents during normal wakefulness or in adults during sleep. They are not observed in healthy awake adults! Theta waves are prominent over frontal-central areas. Wave type Frequency Amplitude Delta 0.5 - 4 Hz Up to 100 μV Teta 4 - 7 Hz Alpha 8 - 13 Hz 20 - 40 μV Beta 13 - 30 Hz 10 - 30 μV Delta waves (0.5 - 4 Hz): They are seen in infants and children during wakefulness or in adults during sleep. They are not observed in healthy awake adults. Prominent over frontal areas. During nonREM stage 3, there is simultaneous, low frequency activity in a large number of pyramidal neurons → synchronized activity of sleep This results in high amplitude, low frequency delta waves. ANATOMY AND PHYSIOLOGY OF EMOTIONS  Studies involving localized brain lesions or electrical stimulation make it clear that distinct brain circuits mediate emotions. Brain regions involved in emotions are: Cerebral neocortex Limbic system Hypothalamus Brainstem 1. External stimuli are detected by sensory systems: Visual, auditory, somatosensory, olfactory, gustatory 2. Afferent sensory axons carry the sensory information to the limbic system (emotion systems, subneocortical system). Emotion systems are activated: This connection is responsible for the formation of affect! Affect forms before the conscious perception of the emotion. Hypothalamus and Brainstem 3. Afferent sensory axons also carry the sensory information to the primary sensory cortices and association cortices in the cerebral neocortex: Conscious perception of the sensory stimuli! 4. Axons eminating from neocortex reach limbic system (emotion systems, subneocortical system): Emotion systems are activated. Hypothalamus and Brainstem 3. Outputs of emotion systems (limbic system) are carried to the hypothalamus and brain stem. 4. Neurons in the hypothalamus and brainstem activate the somatic and autonomic motor neurons in the spinal cord and autonomic ganglia. 5. Somatic motor neurons regulate the contractions in the skeletal muscle cells. Autonomic motor neurons regulate the contractions in the smooth muscle and cardiac muscle cells (physical components of emotions). 6. Hypothalamus also regulates hormone release from endocrine glands (physical components of emotions). Neocortex (Prefrontal Cortex): Receives sensory information from the sensory organs: Conscious perception of sensory stimuli (mental component of the emotions) is formed. Receives information from limbic (subneocortical) regions: Conscious perception of emotions is formed. Receives sensory information from the periphery (internal organs and skeletal muscles): This feedback concerning the skeletomotor and autonomic changes in the body regulates the conscious perception of emotions. Sometimes our thoughts can regulate our emotions: There are projections from the neocortical areas to the limbic system. Sometimes our emotions can regulate our thoughts and behaviors: There are projections from the limbic system to the neocortical areas. Hypothalamus and Brainstem BRIEF ANATOMY OF NERVOUS SYSTEM  ORGANIZATION OF THE HUMAN BRAIN 1. Brain stem: Medulla oblongata, Pons, Midbrain (Mesencephalon) 2. Diencephalon: Hypothalamus, Thalamus 3. Telencephalon: Limbic system, Basal Ganglia, Neocortex.  TELENCEPHALON 1. Cerebral cortex (neocortex + limbic cortex): Neocortex covering the surface of the frontal, parietal, temporal and occipital lobes + Limbic cortex 2. Subcortical regions included in the telencephalon: Some limbic areas (amygdala, septal nuclei) and basal ganglia [eg: dorsal striatum, ventral striatum (nucleus accumbens)]  BRAIN REGIONS INCLUDED IN LIMBIC CORTEX Cingulate cortex, parahippocampal cortex, hippocampus, entorhinal cortex, perirhinal cortex, piriform cortex Cigulate cortex  Cerebral cortex: – Neocortex (shown as white): The LIMBIC CORTEX most recently-evolved part and the outermost layer of the cerebral cortex. It has 6 layers. – Limbic cortex (shown as pink): It lies beneath the neocortex. It has 3- 6 layers. Limbic system and the limbic cortex is phylogenetically the oldest part of the brain. The surface area of neocortex in mammals has expanded extremely, whereas the limbic cortex has changed very little during evolution. Phylogenetics: Study of evolutionary relationships among species, individuals or genes. Limbic System: Limbic structures included in the diencephalon: Thalamus and hypothalamus  NEOCORTEX LIMBIC SYSTEM Conscious perception of the stimuli: Formation of emotions → Discrimination of the objects by motivation → motivated behavior touch, faces and objects by vision is regulated. and sounds by audition. Regulation of the autonomic Intellectual skills (related to nervous system activity. thinking: We distinguish, combine, Regulation of the stress response. classify, analyze, and quantify objects, events, and symbols. So, Learning and memory, storage of reasoning (mantıklı düşünme), problem implicit memory. solving, concept formation, creative Regulation of reproductive thinking emerge. behavior. Language skills: Writing, reading, Thirst and drinking water listening, speaking Behaviors related to Decision making, planning of our thermoregulation. conscious behavior Regulation of food intake Storage of long-term explicit memory. Olfaction LIMBIC SYSTEM EMOTIONS Emotions – Feelings: They are not the same!  EMOTION Emotion is a general term, which also involves «feeling» and «affect». It is a subjective mental state that is usually accompanied by distinctive feelings, behaviors and involuntary physical changes. Emotions are largely unconscious responses. However, emotions may also be consciously perceived. Emotions are triggered when the brain detects an emotionally significant stimulus.  NEUTRAL & SIGNIFICANT STIMULI Stimuli that do not trigger emotions are called neutral stimuli. Stimuli that trigger emotions are called significant stimuli. Significant stimuli that trigger emotions even in the absence of previous experience are called naturally significant stimuli: Noxious, painful, high intensity (eg. auditory) or delicious stimuli etc. Insignificant (neutral) stimuli that occur in conjunction (together) with naturally significant stimuli can acquire emotional significance through associative learning. Emotions have two kinds of components: 1. Physical components 2. Mental components  Physical Components I. Changes in the autonomic nervous system activity: ANS regulates the involuntary activities of our internal organs. Sympathetic activity: Increases heart rate Increases blood pressure Increases sweating Widens the airways (makes breathing easier) Causes dilation of the pupil (mydriasis) Relaxes bladder, micturition reflex is suppressed  Physical Components Parasympathetic activity: Decreases heart rate Decreases blood pressure Causes airway narrowing Increases digestion Causes constriction of the pupil (miosis) Contracts bladder One hypothesis suggests: Positive emotions (e.g., joy or happiness) increase parasympathetic activity. Negative emotions (e.g., anger, anxiety, fear, sadness) increase sympathetic activity. Another hypothesis states: All emotions with high intensity can trigger sympathetic activity.  Physical Components II. Changes in the somatic nervous system (SNS) activity: SNS regulates the voluntary activity of our skeletal muscles. Skeletal muscles contract → mimics, gestures, postures (fight, flight, freeze, startle etc.) III. Endocrine changes: Stress response may be initiated. In the adrenal glands, secretion of cortisol and adrenaline increases!  Mental Components I. Affect: It is the unconscious experience of the stimuli. Emotionally significant stimuli, first, initiate the affect. Affect always develops before conscious perception of the emotion! Affect is innate; it is not acquired through learning. Affect is not expressed verbally. It develops by the activity of the limbic brain regions.  Mental Components II. Cognition (Biliş): It is the conscious perception and discrimination of the specific emotion. It is being aware of the stimuli or thoughts leading to a specific emotion. Cognition is the result of the activity in the prefrontal cortex. Conscious perceptions of emotional responses are called «feelings». Feeling is the conscious experience, interpretation and naming of cognitive, endocrine, autonomic and somatic changes which occur during emotions. Feeling is subjective: The individual compares the current emotional experience with the past experiences and names the current experience accordingly.  Mental Components Affect is distinct from feelings because when affect is first triggered, conscious perception of the emotion is not yet present and it is not yet labeled according to our past experience. Some psychologists suggest that babies do not have feelings because babies do not have past experience. However babies have affect! How can we observe the existence of affect in a baby? Naturally significant stimuli trigger some autonomic and somatic responses in the baby: Mimics, gestures, vocalizations, changes in the respiration and heart rate etc.  Mental Components How can we observe affect in an adult? When a sudden and strong stimulus is applied, uncontrollable physical and autonomic responses are triggered before the conscious perception. These responses reflect the affect. Sometimes, Affect is defined as the quantitative dimension of the emotions Feeling is defined as the qualitative dimension of the emotions. Affect involves autonomic and behavioral responses. Therefore, affect is observable and can be measured using instruments. On the other hand, feelings can be tested only using verbal communication.  Mental Components III. Motivation (conation): Emotions have motivational properties, so that they initiate goal-oriented behavior. How? Emotions are catogorized according to their valence: Positive valence (pleasant, liking) corresponds to the attractiveness of emotion, making it desirable: Joy, love, satisfied Negative valence (unpleasant, dislike) corresponds to the aversiveness of emotion, rendering it undesirable: Sadness, anger, fear Stimuli associated with pleasant emotions trigger approach behavior. Stimuli associated with unpleasant emotions trigger avoidance behavior. FOUR THEORIES WHICH ATTEMPT TO EXPLAIN HOW EMOTIONS ARISE Do we run away from the bear because we are afraid? OR Are we afraid because we run away?  I. FOLK PSYCHOLOGY: First, the stimuli is perceived and interpreted consciously (danger) → Following the conscious perception of the stimuli, the conscious perception of the emotion (fear) arises → Then, autonomic, somatic and endocrine responses are triggered. Folk psychology suggests that conscious perception of the emotion («feelings») triggers the autonomic reactions. I was so angry that my stomach hurts. I was so embarrassed that my face got red.  II. William James - Carl Lange Theory (1880s): First, the stimuli is perceived and interpreted consciously (danger) → Following the conscious perception of the stimuli, autonomic, somatic and endocrine responses are William James 1842 – 1910 triggered → Then, conscious perception of the emotion American Psychologist (fear) arises. Bodily changes evoke conscious perception of emotions: We are afraid because we run! So, different combinations of bodily (autonomic and somatic) responses trigger different emotions (feelings). Carl Lange 1834 – 1900 Danish Medical Doctor  III. Cannon-Bard Theory (1900s): Most of the time, autonomic changes accompanying emotions seem very much the same, whether the emotion is anger, fear or surprise. First, the stimuli is perceived and interpreted Walter Cannon (1871-1945) American Physiologist consciously (danger) → Following the conscious perception of the stimuli, cerebral cortex simultaneously decides on the appropriate emotion (emotion is consciously perceived) and also activates the sympathetic nervous system. Conscious perception of emotion and autonomic activity changes are independent processes. Philip Bard (1898-1977) American Physiologist  4. Schachter’s Cognitive Theory (1960s): First, the stimulus is perceived and interpreted consciously (danger) → Following the conscious perception of the stimuli, conscious perception of the emotion and activation of somatic and autonomic activity occur simultaneously. However, these autonomic and somatic responses also regulate the conscious perception of the emotion. They contribute especially to the intensity of emotion. Previous emotional experiences affect future interpretations of stimuli! Jerome Singer Stanley Schachter (1934-2010): (1922-1997): American American Psychologist Psychologist  A famous experiment by Schachter and Singer (1962): All subjects were injected with adrenaline. Adrenaline increases heart rate in all subjects. These subjects were separated into 2 experimental groups: 1. Subjects in one of the groups were told that their heart would race. People who are warned of the reaction reported no emotional experience, although their heart rate increased! This result supported Cannon-Bard theory. 2. Subjects in the other group were were not forewarned. Some of these subjects experienced an emotion when their heart rate increased! This result supported James-Lange theory. In the second group, there was also a confederate in the room acting in a happy or angry manner: The subjects who experienced a particular emotion reported feeling angry when in the presence of an angry confederate! The subjects who experienced a particular emotion reported feeling happy when in the presence of a happy confederate! These results contradict the James-Lange theory which states feelings of anger or happiness should each be initiated by a unique group of autonomic reactions. Schachter’s Cognitive Theory: An emotional state is the result of an interaction between the autonomic/somatic responses and conscious perception of the emotion. However, individuals interpret bodily changes in terms of the eliciting stimuli, the surrounding situation (context), their cognitive states and their past experience.  THE PURPOSE OF EMOTIONS Mimics and gestures, the somatic components of emotions have important functions during communication among individuals. We signal others about how we react to a stimulus by using mimics and gestures. For example, mothers smile to show approval and encourage their children on the right path or they frown to show disapproval.  EXPRESSION OF EMOTIONS Basic expressions of emotions are displayed in all cultures: They are universal. Which stimulus trigger which emotion? How do we express our emotions? They both are partly inherited and partly acquired through learning. Human mimic muscles are innervated by Facial Nerve: Cranial Nerve VII  Paul Ekman, American Psychologist Dacher Keltner, American Psychologist Paul Ekman (1934) and his collaborators have developed analytical tools for the objective description and measurement of facial expressions among humans of different cultures. How many different emotions can be detected in facial expressions? Basic emotions suggested by Keltner and Ekman are anger, sadness, happiness, fear, disgust, surprise, contempt and embarrassment.  Russell et al. 1994: Within Western and non-Western literate groups (left) there is widespread agreement about the emotions represented by photographs of basic facial expressions. But people from isolated nonliterate groups (right) are much less likely to agree with Western judgements of some facial expressions, especially those of surprise and disgust.  Cultures prescribe rules for facial expression and they control and enforce those rules by cultural conditioning. Cultures affect the display of emotion! Some cultures limit/restrict the display of emotions whereas others encourage it.  According to Allan J. Fridlund (1994), a major role of facial expression is paralinguistic: That is, the face is accessory to verbal communication, providing emphasis and direction in conversation. Facial cues are "social tools" that modify the trajectory (direction) of our social interactions. Research performed by Gilbert (1957) and Kraut and Johnson (1979) supported this hypothesis. Gilbert (1957): Subjects display few facial responses to odor when smelling alone, but significantly more in a social setting. Kraut and Johnson (1979): Bowlers seldom smile when making a strike, but they frequently smile when they turn around to meet the face of onlookers.  LIMBIC SYSTEM: FEAR Pablo Picasso (Weeping Woman) Oswaldo Guayasamin (Fear)  Kluver-Bucy Syndrome Kluver-Bucy syndrome was described by the psychologist Heinrich Klüver and neurosurgeon Paul Bucy in 1938. They removed anterior portions of the temporal lobes including the amygdala and hippocampus of monkeys. The animals’ behavior changed dramatically after the surgery.  Kluver-Bucy Syndrome The most prominent change was an extraordinary «taming» effect. Animals that had been wild and fearful of humans prior to surgery became tame and showed neither fear nor aggression afterward. This condition is also described as flattening of emotions. Operant fear conditioning is imparied: They could not learn to press a lever to avoid electrical shocks. In humans, this syndrome may be caused by trauma, degenerative brain diseases, tumors, or brain infection. FEAR CIRCUITRY FEAR 1. Innate fears (unconditioned fears): We are born with such fears. They are inherited. Two innate fears in humans are: Fear of falling Fear of loud sounds Many animals rely on innate olfactory signals in the detection of threats. For example, rodents exhibit freezing and other defensive behaviors when fox urine is detected. 2. Conditioned fears: Most fears are learned!  ROLE OF AMYGDALA IN FEAR REGULATION Amygdala plays an important role in the formation of both the innate and learned fear. Electrical stimulation of amygdala causes fear reaction! Amygdala lesions cause an extraordinary taming effect; innate and conditioned fear responses are impaired.  ROLE OF AMYGDALA IN IN FEAR REGULATION Fear has a negative valence. Amygdala associates neutral stimuli with fear. So, previously neutral stimuli now become undesirable: Fear conditioning On the other hand, amygdala is also involved in the processing of rewards: Amygdala is required for associating neutral stimuli with rewards.  INNATE FEAR RESPONSE 1. A noxious (harmful or unpleasant) stimulus activates sensory pathways: For example: Loud noise activates auditory receptor cells in the inner ear (cochlea) 2. Auditory information is carried to the thalamus by sensory afferent fibers. Auditory information terminates in one of the specific thalamic nuclei: Medial geniculate nucleus  INNATE FEAR RESPONSE In parallel with Cannon-Bard theory, auditory information is carried from thalamus to 2 brain regions: 1. Amygdala (limbic system) 2. Specific primary auditory cortex: Lateral Auditory information is nucleus transmitted from the primary auditory cortex to the Association Cortices → Conscious perception of sounds and danger! As a result, amygdala and cortex are activated simultaneously.  INNATE FEAR RESPONSE Fear response is activated in the amygdala through two distinct pathways: 1. Direct pathway from thalamus to the amygdala triggers fear response much faster, before the conscious perception of fear! 2. Indirect pathway from cerebral association cortex to the amygdala triggers fear response much slower than the direct pathway.  INNATE FEAR RESPONSE Fear circuitry in the amygdala: Information related to fear is conveyed from cerebral association cortex or thalamus to the Lateral lateral nucleus in the nucleus amygdala. Thereafter, it is carried to the central nucleus (CeA). Threatening stimuli trigger defensive behavioral responses: 1. Active behavioral strategies: Escape (flight, running, hiding, avoidance) Jumping Defensive attack (fight) They are accompanied by increased sympathetic activity: Increased heart rate and blood pressure. 2. Passive behavioral strategies: Immobility or freezing They are accompanied by increased parasympathetic activity: Decreased heart rate and blood pressure.  CLASSICAL (PAVLOVIAN) FEAR CONDITIONING An association is learned between an unconditioned stimulus (US) and a conditioned stimulus (CS). Unconditioned stimulus, US): Electrical foot shock (pain) Conditioned stimulus (CS): Tone (sound) An emotionally neutral CS (tone) is presented for several seconds and the animal is shocked (US) during the final second of the CS.  CLASSICAL (PAVLOVIAN) FEAR CONDITIONING At the beginning, only foot shock (US) triggers the responses in the organism: Unconditioned Responses (UR) Freezing Eyeblink Startle Increased blood pressure and heart rate (increased sympathetic activity) After several pairings of the tone and shock, presentation of the tone (CS) alone elicits these motor responses, which are now called the conditioned responses (CR). Amygdala plays a key role in Pavlovian fear conditioning: Sensory information associated with sound (CS) and pain (US) is relayed to the specific sensory nuclei in thalamus (Medial geniculate nucleus for sound; Ventral posterior nucleus for pain). Specific sensory nuclei (auditoy and somatosensory nuclei) in thalamus send the sensory information to the lateral nucleus of amygdala and the specific primary sensory (auditory and somatosensory) cortices. Sensory and association cortices also relay the signals to the lateral nucleus of the amygdala. Medial geniculate nucleus Ventral posterior nucleus  CS and US signals converge in the lateral nucleus of amygdala! When the CS (tone) is applied alone, a small electrical response is obtained in the neurons of the lateral nucleus. On the other hand, when the CS (tone) and US (pain) are paired (applied close together in time), the electrical response of the neurons in the the lateral nucleus increases; so the effectiveness of the CS is enhanced. Convergence of CS and US pathways in the lateral nucleus neurons leads to synaptic changes which produce the increase in the response.  The lateral nucleus projects to the central nucleus of amygdala. Damage to lateral or central nuclei in animals impairs fear conditioning. The central nucleus then connects with brain regions that control the motor responses (physical components of emotions): 1. Brainstem nuclei: Motor nucleus of nervus vagus: Regulates parasympathetic activity such as decreased heart rate during freezing, increased defecation and urination. Motor nucleus of nervus facialis: Regulates mimics Nucleus reticularis pontis: Regulates startle PAG 1. Brainstem nuclei (continued): Parabrachial nucleus (PB): Increased respiration Locus coeruleus (LC): Increased sympathetic activity and wakefulness. Laterodorsal tegmental nucleus (LDT): Increased wakefulness Periaquaductal gray (PAG, central grey): Involuntary defensive reactions are triggered; freezing (immobility), fight or flight; different subregions of PAG activate different responses. 2. Hypothalamus: Direct connections from CeA to lateral hypothalamic area increase sympathetic activity. Direct connections from CeA to paraventricular nucleus induce the stress response (cortisol secretion).  Le Doux et al. 2016 Besides CeA, lateral nucleus of amygdala also projects to the basal nucleus, which connects to the Striatum (Nucleus Accumbens): Direct connections from basal nucleus to NAc control the performance of voluntary actions, such as escape and avoidance. This pathway is responsible for operant fear conditioning such as active avoidance leraning.  ACTIVE AVOIDANCE CONDITIONING «Active avoidance» is a type of aversive operant conditioning. Subjects learn to avoid an aversive stimulus by initiating a specific locomotor response: Negative reinforcement! Axonal projections from basal nucleus of amygdala to the nucleus accumbens play an important role both in aversive operant conditioning. Conditioning (training): Rat is placed in a two-compartment shuttle box. Rat has to learn the association between a conditioned stimulus (sound) and an unconditioned stimulus (footshock).  ACTIVE AVOIDANCE CONDITIONING Conditioning Phase: At the beginning, sound does not trigger a response. However, when footshock is delivered, rat escapes by moving to the opposite compartment: Unconditioned response (UR), escape response Post-conditioning test trial: When CS (sound) is presented, animal avoids to receive the shock by moving to the opposite compartment. This is called as conditioned response (CR): Avoidance response  Long-term memory concerning the emotions (eg. fear) is stored in amygdala. Amygdala plays an important role in the recognition of emotions (especially fear) in the facial expressions. PET (positron emission tomography) scan, rCBF: regional cerebral blood flow Urbach-Wiethe Disease: A genetic disorder that causes the accumulation of calcium salts in the amygdala. Damage to the amygdala starts at early ages. Fear responses and fear conditioning are impaired. Patients cannot discriminate emotions (especially fear) in the facial expressions! However, they can recognize the faces.  CINGULATE CORTEX AND PREFRONTAL CORTEX CONTRIBUTE TO EMOTIONAL PROCESSING Medial prefrontal cortex (mPFC) is located in the medial aspect of the cerebral hemispheres. It involves ventromedial PFC (vmPFC). Anterior cingulate cortex (ACC) is included in the vmPFC Lateral view of the right hemisphere. mPFC is marked with green Lateral view of the right hemisphere. Lateral view of the right hemisphere. vmPFC is marked with green Cingulate cortex is marked with green  There are efferent pathways from basolateral (lateral and basal nuclei) amygdala to the mPFC. These pathways play an important role in the: Conscious perception of fear Regulation of our decisions and behaviors by fear vmPFC and ACC have strong connections with the limbic system (basolateral amygdala, hypothalamus and PAG): Formation of innate and conditioned fear mPFC mPFC Tasan et al. 2015  Different subregions of mPFC and ACC have different roles in aversive learning and decision making: 1. Appraisal of fear-relevant stimuli: Evaluation of the meaning of a stimulus to the organism. Is the stimulus dangerous? How dangerous is the stimulus for the organism? 2. Expression of fear conditioning and innate fear. 3. Activation of fear-associated autonomic responses. 4. Inhibition of fear and anxiety and induction of fear extinction.  ANXIETY Fear and anxiety are related emotions. They are both negatively valenced emotions. However, they are not the same! Anxiety (apprehension) is a vague sense of worry or uneasiness. It is often a response to a poorly defined or unknown threat. For example: Uneasiness you might feel walking down a dark street alone. Fear is focused on a known external danger; danger is real and immediate. For example: When you're walking down a dark street, someone points a gun at you and says, “This is a robbery”. Studies suggest that fear and anxiety pathways largely overlap! (Calhoon and Tye 2015, PMID: 26404714) NEURONAL CIRCUITRY OF AGGRESSIVE BEHAVIOR  AGGRESSIVE BEHAVIOR - RAGE It is defined as overt (clear) behaviour that has the intention of imposing physical damage on another individual. Aggression is an innate social behavior essential for resource (food, water, territory) and mate competition, self-defense, and protecting family. Aggressive behavior is studied mostly in cats and rodents. Two subtypes of aggressive behavior is identified in animals: Defensive aggression («korumacı agresyon») Predatory attack («yırtıcı saldırı»)  DEFENSIVE AGGRESSION It occurs in response to the presence of a threatening stimulus. It is related to self-defense. It is accompanied by high sympathetic activity. It is usually aversive. However, it may be rewarding for a dominant male. Physical Signs: Arching of the back Retraction of the ears Increased sympathetic activity: Piloerection (erection of the hair of the skin), pupillary dilation (mydriasis) Vocalization (hissing or growling): Threatens the enemy Striking of the target species with the forepaw Biting  PREDATORY ATTACK Predatory attack occurs without any threat. Hunting behavior! The attack is planned. Specific prey object is stalked quitely. The prey is usually captured by biting the back of the neck: Quiet biting! Sympathetic activity is low: Mild pupillary dilation, no piloerection. It is rewarding: It has positive reinforcing effects!  CATEGORIZATION OF AGGRRESSIVE BEHAVIOR IN HUMANS 1. Reactive (impulsive) type : It occurs in response to a threat: Related to self-defense It is usually associated with anger. It is impulsive. Impulsive behavior: Displaying behavior characterized by little or no forethought, or without considering the consequences. Sympathetic activity is high. For example: To hit someone who insulted you 2. Instrumental (controlled) type: It is goal-directed, planned and performed to achieve a desired outcome. It is accompanied by low sympathetic activity. Mass killings, genocides or assassinations… LABORATORY TESTS FOR MEASURING AGGRESSIVE BEHAVIOR Resident-Intruder paradigm : Individuals of the same species (conspecifics) are used for measuring defensive aggression. Individuals of different species are used for measuring predatory attack (cat- rat, rat-mouse, rat-insect).  DEFENSIVE RAGE AREA IN HYPOTHALAMUS Coronal sections CAT Red: defensive rage area RAT Red: defensive rage area Electrical stimulation of medial hypothalamus (hypothalamic attack area) produces defensive rage: Biting attacks on conspecifics (individuals of the same species) Ventromedial hypothalamic nucleus (VMH) plays a key role in the regulation of defensive rage. The activity of VMH neurons induces aggressive behavior. Majority of VMH neurons are glutamatergic (GLUT). Estrogen and androgen receptors are expressed in VMH: Their activity increases aggressive behavior in males.  Lischinsky ve Lin 2020 PATHWAYS FOR DEFENSIVE RAGE In rodents, olfactory stimuli trigger defensive rage. Olfactory stimuli → Olfactory pathways → Medial Amygdala (MeA) → VMH → PAG In humans: Visual and Auditory stimuli → Visual and auditory pathways → Primary visual or auditory cortices → Association Cortices (Prefrontal Cortex) → Amygdala → VMH → PAG  Lischinsky ve Lin 2020 Core Aggression Circuit (CAC): Medial amygdala (MeA) + Bed Nucleus of Stria Terminalis (BNST) + Hypothalamus [Ventromedial hypothalamus (VMH), Premammillary nucleus (PMv)] Olfactory stimuli → Olfactory pathways → MeA → BNST → Hypothalamus [VMH, medial preoptic area (mPOA), PMv] VMH and mPOA also have important roles in the regulation of sexual behavior!  OPTOGENETIC STIMULATION OF VMH High-intensity stimulation increases aggressive behavior towards male and female intruders and lab gloves, whereas low-intensity photostimulation of VMH neurons increases mounting behavior. The intensity of the photostimulation determines the social behavior: Close investigation, mounting or attack! Some of VMH neurons are activated by both aggressive and reproductive behavior! These partially overlapping neuron populations control both the aggressive and sexual behavior. The activation level of these neurons may determine which social behavior will be displayed. Lin et al. 2011: Optogenetic activation of VMHvl elicits attack in mice. Lee, Kim, Remedios et al. 2014 VMHvl neurons express ChR2 (channel rodopsin) Hypothalamus (VMH) projects to 2 brain areas: 1. PAG → Brainstem nuclei → Autonomic and somatic activity (mimics associated with aggression, biting, fighting); This pathway is responsible for innate aggressive behavior 2. Ventral tegmental area (VTA) → Striatum; This pathway is responsible for learning of aggressive behavior. If aggressive behavior results in success, it is rewarding; Aggression can be directly learned through operant conditioning (positive reinforcement). The activity of VMH is under tonic regulation by lateral septum (LS); if lateral septum is lesioned septal rage is induced in rodent.  NEURAL PATHWAYS MEDIATING DEFENSIVE RAGE (Visual, Auditory) PAG: VMH GLUT neurons project to dorsal PAG and initiate attack behavior. Olfactory pathways (Amygdala) PAG neurons project to several brainstem nuclei: 1. Nuclei that control autonomic activity: Activity of the sympathetic neurons is increased. 2. Nucleus of the trigeminal nerve (CN V): Activates muscles of the jaw required for vocalization and biting. 3. Nucleus of the facial nerve (CN VII): Activates mimic muscles; facial expressions 4. Nuclei which give rise to the reticulospinal tract: This tract innervates the motor neurons which activate the muscles of the forelimbs required for fighting.  Rodent Brain Human Brain PREFRONTAL CORTEX Stimulation of the mPFC in cats and rodents supresses aggressive behavior. Lesions of the mPFC in rats and humans increase aggressive behavior. Pyramidal neurons associated with aggression in the mPFC project mainly to the amygdala, hypothalamus and PAG. Pyramidal neurons in the mPFC inhibit aggressive behavior. REWARD CIRCUITRY  Motive: «Güdü» Motivation: «Güdülenme» Our motivations are described as «wants» or «needs» that direct behavior toward a goal. It expresses our internal states ranging from «wanting something very much» to «avoiding something completely». Motivations may be conscious or unconscious. Motivations may be inherited or may be learned. Motivations shape our emotions, conscious thoughts and behavior.  Motivations and emotions are closely related. In many cases, emotions have a motivational component: Emotions motivate individuals to perform certain behaviors. For example: If you are happy, you are energized to do something that you believe will help you maintain the happy feeling. If you are angry, you may be motivated to act aggressively against the person who made you angry.  Some of the significant stimuli in our external environment are categorized as «rewarding». Clark Hull Animals and humans are motivated by rewards. There are 2 types of rewards: 1. Natural rewards: Food, social interaction, sex, exercise etc. 2. Drugs of abuse (abuse: süistimal, kötüye kullanım) Robert C. Bolles Rewards have 3 components: I. They have a hedonic impact: They produce pleasure (liking). II. They are wanted: They produce approach behavior. III. They promote learning: Terry Robinson When a neutral stimulus (CS) is paired with a reward (US), it triggers reward effect: Conditioned learning Rewards increase the frequency of actions that produce them: Positive reinforcers Kent Berridge In the brain, rewarding and aversive stimuli activate «Reward» and «Aversion» Systems, respectively: 1.These systems are regulated by different neural pathways. 2.They regulate our emotions: Emotions with positive valence (emotions which we like): Joy, euphoria etc. Emotions with negative valence (emotions which we dislike): Anger, rage, fear, anxiety, dysphoria etc. 3.They regulate our motivations: Motivations range from «wanting» to «avoiding». Stimuli, which activate the Reward System, generally produce positive emotions and trigger «wanting and approach behavior». Stimuli, which activate the Aversion System, generally produce negative emotions and trigger «aversion and escape/avoidance behavior» REWARD PATHWAY  DOPAMINERGIC PATHWAYS IN THE BRAIN Dopamine neurons (DA) are implicated in the reward system. They are found in 2 brain regions located in the midbrain (mesencephalon): 1. Ventral tegmental area (VTA) 2. Substantia nigra (SN)  1. Mesocorticolimbic pathway: DA neurons in the VTA project to the limbic system and PFC and release DA in these brain areas. Major projection areas: I. Nucleus accumbens (NAc, Ventral striatum): Mesolimbic system (green) II. Prefrontal cortex (PFC): Mesocortical system (orange). Medial PFC (mPFC) regulates our motivations. 2. Nigrostriatal pathway (red): The axons of the DA neurons in the SN project to the dorsal striatum (caudate, putamen). This pathway plays an important role in the planning and execution of voluntary movement. Mesocorticolimbic and nigrostriatal pathways play an important role in reward.  James Olds Peter Milner Intracranial self-stimulation An electrode is implanted into the VTA, NAc or prefrontal cortex. Whenever the rats press a lever inside the cage, an electric current is applied to these brain areas. Electric current increases the release of dopamine in the NAc or PFC. Therefore, lever press is rewarding and triggers wanting/pleasure. The rats learn to press the lever in a short period of time (operant conditioning) and the number of lever press is increased: Positive reinforcement Reward System in Physiology: It plays a key role in the «wanting», pleasure or positive affect induced by food, our thoughts, behaviors and social relations with our family and friends. It plays a key role in the development of our motivations. Reward System in Disease: Reward system plays a key role in the development of addiction and substance abuse. Drugs of abuse directly activate the dopamine neurons in the VTA, thereby, increase dopamine release in the NAc and mPFC. ADDICTION Burada bağımlılığı «compulsive behavior» üzerinden açıklamışım. Ancak sonra dersi kısaltayım diye bağımlılık evrelerini tarif ederken compulsive behavior nasıl gelişir Şeklindeki açıklamaları attım. Bu arada okuduğum Kaynaklara göre operant behvior’ın başında, conditioned behavior henüz öğrenilirken, Nac devrede ancak öğrenme tamamlandığında ve henüz conditioned behavior goal-directed iken DST’nin medial kısımları (DMS) anahtar rol oynuyor. Davranış compulsive olduğunda (habit) o zaman da DST’nin lateral kısımlar (DLS) anahtar rol oynuyor. TIP DERSLERİNE BAK!!! How do we diagnose addicti