PSYC 304 Midterm 2 PDF

#separator:tab #html:true "what happens when a neurotrnasmitter molecule binds to a postsynaptic receptor? " "it can have one of two localized effects:1. Depolarize the membrane (decrease membrane potential from -70 mV to -67mV)2. hyperpolarize the membrane (increase the membrane potentia...

#separator:tab #html:true "what happens when a neurotrnasmitter molecule binds to a postsynaptic receptor? " "it can have one of two localized effects:1. Depolarize the membrane (decrease membrane potential from -70 mV to -67mV)2. hyperpolarize the membrane (increase the membrane potential from -70 to -72) " "Depolarize the membrane and hyperpolarize the membrane names " "Depolarize= excitatory postsynaptic potential (EPSP)Hyperpolarize= inhibitory postsynaptic potential (IPSP)--> aka changes of voltage on the dendrites " "EPSP+ IPSP " "-Increase likelihood that the postsynaptic neuron will fire an action potential (AP)-Decrease the likelihood that the postsynaptic neuron will fire an AP " "How does the transmission of post synaptic potentials occur? " "-It is graded: rapid and decremental: they travel like an electrical signal along an uninsulated wireGraded: not all the same shape or size, the increase ins EPSP means an increase in amplitude-> STRENGTH THROUGH AMPLITUDE--> Depends on how many neurotransmitters bind to receptorsRapid: Signal spreads supa fastDecremental: Decays the further u get form the site " "EPSP and IPSPs sum both _ " "spatially and temporally " "Summation over space " "- Need several EPSPs to do reach an action potential --> Two simultaneous EPSPs sum to produce a greater EPSP-Two simultaneous IPSPs sum to produce a grater IPSP-A simultaneous EPSP and IPSP cancel each other out-This means that IPSPs are working against you " "Summation temporally " "-Two ESPS in RAPID succesion produce a larger ESPS ---> SECOND esps beofre the 1st ESPS decays--> same for IPSPs-Furhter away from axon means weaker, so interneurons are usually closer to the axon for the bigger effect " "AP generation " "If the sum of the ESPs and IPSPs that reaches the axon initial segment (beginning axon) is sufficient to depolarize the memebrane there above its thershold of excitation then an AP is generated-The AP is a massive momentary reversal of membrane potential (-70 to +55) " "what is action potential " "-It reverses the polarity-it  is a rapid, brief reversal of the polarity at the membrane, frome negative to positive- it is the main method of brain communication***-It's all or nothing NOT graded (0-100%)--> always the same size/shape in a cell- happens becaus of threshold!!!!! " "what happens at the threshold " "-AP generation and conducion are both the result of voltage-activated ion channels (primarily Na\(v\))-These channels are closed at rest, but when it reaches the threshold (-55mV) there is a conformational change " "Small depolarizations " "-Na+ channels are usually closed, but they are voltage gated---> they are closed until they reach a certain voltage (~-55mV)Which direction does Na+ want to flow and why- remember Na+ is flowing INTO the cell.. remeber gradients!!!!!-From the outside to the inside (more on the outside so it flows inside)--> Chemical gradient-Electrical: INside of the cell is more negative-> pushing Na+ from the outside to the inside-BOTH are pishing Na+ into the cell---> DEPOLARIZATION PHASE--> just sodium coming into the cell " "Rapid huge depolarization: what is happening in these sodium channels " "-Na+ channels open-> Na+ into the cell--> cell membrane flips from neg. to pos.--> BUT Na+ channels have built in inactivation (no Na+ but not closed) is it like a plug with a ball and chain- piece of protein tat is a combo of right suze and shape------> shut off automatically after ~1ms-Na+ channels stay inactivated until membrane goes back to resping potential-- ONLY if it goes back to closed (RMP) it will get usback to another AP----> NO MORE action potentials until reset!!!!!!--> this leads to the absolute refractory period... the moment the ball is there, you cannot fire another AP " repolarization -K+ leak channels, as always, are OPEN-BUT even more K+ channels open during AP (VOLTAGE GATED NOT NORMAL K CHANNELS)-Membrane is now postive so which way does K+ flow? OUTSIDE at the peak of the AP the inside is now postive so, it is trying to return the cell to neg. resting membrane potential- CHEM AND ELECTRIC pushing K out.-Slow closing od voltage-gated K+ channels leads to hyperpolarization phase and the relative refractory period-Na+/K+ pump restores ion balance over time, so since it is SLOW it has no effect on AP!!!!! Hyperpolarization -For a short time the membrane is more leaky so it causes more K+ to be pushed out more and this causes the hyperpolarization phase-- EXTRA k+ leaving the cell--This is a chance for AP to fire again once this phase goes away. The speed of when anpther AP occurs depends on the EPSP and how STRONG the signal is. Strong signals cause AP--> HIGHER frequency. What is the effect of a SUBthreshold stimulation of an axon -An excitatory potential is produced but it is not efficient to elicit an AP What are the effects of SUPRAthreshold  An excitatory potential is produced that exceeds the threshold of excitation and produces an AP that continues down the axon--This is called conduction what does conduction look like in an unmyelinated axon -Na+ channels are present all along the axons---> unmyelinated axons means Na+ channels are everywhere-This causes a SLOW signal and SLOWER conduction and we dont want that we want FEWER Na+ but not TOOOOOO few. Axon myelination -insulating substance SUPERRRRRR fast-reduces how much is lost-At the NODE of ranvier is where there are na+ channels--> The gap btwn the myelin sheaths.... this means... FEWER CHANNELS!!!! conduction in a myelinated axon -Na+ channels are present alonf the axon ONLY at the nodes of ranvier--> they spread under the myelin sheath whcih means its supa fast Speed and direction in action potential AP is faster down M axon vs unM axon... why? TWO reasons-Fewer Na+ channels---> AP spending more time travelling at the speed of lightWhy does AP only travel in one direction?-Na+ channel because early un the axon are in the INACTIVED gate and cannot let anymore Na+ in so this is the MAIN reason why this Na+ inactivtion has been perserved... only one direction What happens at the end of axon -axon ends in terminal boutons-they have vessicles FILLED with neurotransmitters-Action potential depolarizes bouton (want to trigger neurotransmitter)--> causes voltage gated Ca++ channels to open-> THERE IS A LOT OF CA OUTSIDE OF THE CELL---> Ca++ causes SNARE(flex) complex to activate---> Snare complex fuses the vessicles with membrane--squeezes---> Neurotransmitters released into synapse Synapse working -dendrite membrane has special receptors that fit, like LOCK and KEY with the neurotransmitters-Receptors are often just closed channels that open when they bind with neurotransmitter!--> LIGAND-gated ion channels--> NOT leak channels* The first experiment on hormones: Berthold 1849 -loss of function experiment--Restoration of function with native or donor testes-did not require innervation-Organizational (appearance) and activiational (behavioural) effects ---> DEVELOPMENT and ACTION-Testes makes a secretory blood-borne chemical (travels through here)--3 diff groups of hens, 1 left undisturbed young rooster and it developed normally, 2 had testes removed and during development did not have rooster like qualities, 3 the testes were removed and then reimplanted and it developed like a rooster-Shows that there is a chemical messenger in testes and that it isnt rlly connected to anything (no wires) Secreting chemicals- hormones "-""hormones"" is quite a catch-all--released primarily by glands (but also other tissues-heart, stomach, kidneys)--Released primarily into the bloodstream (but also locally)--> travel far distances--Released primarily by animals (but also plants)Exocrine vs. Endocrine glands-Exo: sweat, tears, salivary glands, relasing things outside of body-Endo: releases hormones into body that changes behaviours" What are the different types of cells that secrete chemicals (6) Neurocrine: Neuronal communicationEndocrine: release hormones into the blood streamAutocrine Releases itself to presynaptic terminals-> negative feedbackParacrine: Sends signals to neighboring cells, the closer the strongerPheromone: outside molecules, for e.x. smelling pee in SAME speciesAllomone: Smelling molecule from DIFFERENT species (bee and flower pollen) Principles of hormone function -Slow acting gradual effects---> SUPER slow, hours, to weeks to see effects, BLOOD to target-Behaviour changes in intensity/probability rather than polarity- likelyhood or intensity of behaviour occuring instead of type of behaviour-behaviour nad hormone release are reciprocal: Can both effect each other-Multipilicty of action: Variety of targets that depends on the tissue and the receptor-Secretion is often pulsatile and rhytmic: When hormones release they are released in PULSES (months, days, circadian rhythm)-Hormones can interact: 2 at the same time will produce a diff effect than one alone-hormones need receptors--> need something to bind to! the hypothalamus and neuroendocrine cells -Hypothalamus (HTh): junction between NS and endocrine system-HTh contains neuroendocrine cells, aka neurosecretory cells--> Blood stream not on to neuron-Some hormones are also neurotransmitters!--> epinephrine and nonrepinphrine Hormone types -Peptide: LARGE string mostly outside of cell-Amine: Small, one segment, SOME can be INSIDE cell...-Steroid: Special at crossing the plasma membrane (INTO cell) Hormone receptor types -At the membrane - i.e. GPCRs, faster --> This is the opposite of NT because it is the slowest of NT but the FASTEST of hormones. --> GPCRs are a G protien on the plasma membrain-these are ALL of our hormone types (pep, amine, steroids)-Intracellular usually near the nucleus - i.e. transcription factor, slower-->Receptors can be inside cell, MOSTLY steroids, but sometime amine.-> transcription factor is changes to transcription of genes (in/de) in proteins being expressed-Note: steroid hormones can have GPCRs, too! methods in measuring hormones and receptors Radioimmunoassay: measure hormone levels at the blood and tell us prevelance of amount of hormones in bloodAutoradiography: looking at brain areas affected by hormoes, take hormone and make it radioactive and then bind it to target, will show radiation on photo paper. Shows where ur radioacitve hormone is binding to***Immunohistochemistry: Creating antibody for receptor, shows where the receptors are in bodyimmnocytochemistry: lvl of cells grown in petri dish, shows where the receptors are in bodyIn situ hybridization: Strand of complimentary RNA that will bind to target RNA and shines (florescence image), shows where hormone receptor rna is. ACTIVATION of transcription-> if cell has RNA Negative feedback mechanisms -ensures not too many NT is being released-happens at every conceivable levelAutocrine: same as autoreceptorstarget cell: Change in probability of behaviour (stress) causes a reduction in hormone release) brain regulation: Can also inhibit the big boss (hypothalamusbrain and pituitary regulation the pituitary gland -The other side of the NS/endocrine intersection-Connected via infundibulum, aka pit. stalk-Anterior and posterior divisions--> these are different tissues during development that relase differnet hormones The posterior pituitary -NO dedicated endocrine cellHTh has neuroendocrine cells in paraventricular and supraoptic nuclei-->Axons that projectAxons travel down infundibulum to posterior pituitaryThese HTh axons terminate on capillariesThese axons release oxytocin and vasopressin/anti-diuretic hormone (ADH) into the bloodOxytocin: stimulate uterine contractions in pregnancy; milk letdown reflexADH: conservation of water; blood vessel constriction--> reduce amount of pee, and help with dehydration or too much salt.Alcohol inhibits L-type calcium channels, which inhibits ADH release--> Causes no release of ADH which is why alcohol makes you pee, because you are blocking ADH!!! the anterior pituitary HTh neuroendocrine cells terminate at median eminence --SHORT axonHTh release releasing hormones--> ACTIVATE the hormonesReleasing hormones carried (only a few mm) via hypophyseal portal veins--> Capillaries to anterior pAnterior pituitary has its own hormone-producing cellsWhen releasing hormones arrive, anterior pituitary cells release tropic hormones---> TROPIC means tharthey cause hormones to release out.Tropic hormones travel to glands and cause further hormone releaseThe common motif: Releasing hormones (HTh) -->tropic hormones (anterior pituitary gland)  -------->hormones (gland) --------------> target  Hormones of the anterior pituitary -6 main ones: TROPIC hormones-Cortico-thyro-gonad-Prolactin-Somacrinin Notable glands: The adrenal gland Adrenal cortex vs. adrenal medulla-> tropic from Anterior to cortisolDifferent inputs to cortex (anterior pituitary) vs. medulla (ANS)Adrenal cortex releases steroid hormones-Cross through membrane: Glucocorticoids (e.g. cortisol), Mineralocorticoids -salt +water retention(e.g. aldosterone), Sex steroids- m v f (e.g. androstenedione), Synthesized on demand via ACTH--NO storing Adrenal medulla releases amine hormones: Epinephrine, Norepinephrine--> this is in the sympathetic nervous system Notable glands: the thyroid gland Releases thyroid hormones: thyroxine, triiodothyronineThese are amines but act like steroids--> means that they cross through PM--> INTRAcellularGenerally, regulate growth and metabolismAlso has a general activating effect on NS--> impairment in cogntion and reflexesOnly substance in the body that needs iodineHypothyroidism--> lack of iodineThyroid also releases calcitonin Notable glands: the pineal gland -NOT target of anterior pituitaryaka Your third eye! (Not really)--> for animals: how long days are (seasons), have photoreceptorsThe seat of the soul? (No)Releases melatonin: hormone, amount of light you are exposed to--> so no light= yay melatoninMelatonin released at night---> For animals: gonad releasing input decreases when there isnt light--->for humans: bright lights inhibit melatonin releaseInputs: from sympathetic NS!--> signal comes from ganglia Notable glands: the gonads Two compartments in male and female gonads: one for sex hormone production, one for gametes productionGnRH and/or GnIH (HTh) --> FSH & LH (ant. pit. blood stream) --> gonads------>sex hormonesAnd kisspeptin (peptide nt) stimulates GnRH--> Puberty, driving factorTestes: Sertoli cells (sperm), Leydig cells (androgens, e.g. testosterone)Ovaries: Ova (mature gametes), Steroid hormones (progestins, e.g. progesterone, and estrogens, e.g. estradiol) Hormones in behaviour? Yes, BUT with notable limitations in humans - i.e. Cortex often supersedes many older controls for behavior.--> conflicts with other controlsThe most vigorous responses are observed in animal models.And the converse is true: behavior influences hormones.e.g. Psychosocial dwarfism--> parental neglect, intense strength, causes person to stop growing. BUT when removed from this environment they grow again! e.g. Oxytocin and vasopressin/ADHExogenous oxytocin in rats: they are close to each other and cuddle each otherOxytocin knock-outs in mice: Social amnesia, wont recognze other mice (even if met before) and with act like they are strangersOxytocin & vasopressin receptors: ventral pallidum (VP)-> Main target of nucleus accumbens (BASAL), so MOTIVATIONAL circuitsPrairie voles vs. meadow voles-->Praire are monogamous and F have a lot of oxy and men and a lot of VP--> Meadow are nonmonogamous and they have low O and Vp in both M and F Is oxytocin a love molecule -its more complicated than we thought-increases in group bias--> only love in group?-increases propensity for revenge!!!- so take with a grain of salt pretty much do pheremones mediate behaviour? -In non human animals: Yes! Via the vomeronasal organ (VNO)--> not main olfactory a diff organ-In humans: not so much, Our VNO and its related genes are basically non-existent ---> some studies like mcclintock and men's swear dont replicate Does stress mediate behaviour? "All animals (plus humans): yes--> BUT part of stress response is central (in the brain)-Dual pathways, HPA axis, Sympathetic NS-Negative feedback to alllll of these above-hippocampus will inhibit hypothalamus-Stress response is interpreted: need t interpret to figure out what it is and this depending on the context of the environment--> experiment to test ""new vitamin:"" put person in a room with a stoog or a grumpy person and this determined how p's interpreted stress" Receptor types -Ionotropic (Channels)-Metabotropic (signaling protiens  Ionotropic AKA Ligand gated ion channels-excitatory (depolarize), AKA EPSPs-Inhibitory (hyperpolarize), AKA IPSPs-Fast, transient effect-->Short lasting effecting, on/off, like controlling muscles or sensory----> NOT eyes-They are mainly used for when you want to do an action or ot be decisive  Metabotropic AKA G protien coupled receptors (GCPR)- String of amino acid, metabolic, no hole or pore-Modulate cell (mau turn up or down)-Modulate signals (increase or decrease)-Slow, longer lasting effect---> Seconds, minutes, hoursCauses signal cascades, spreads out anf activates thousandds of other proteinsturns them on/off or causes channels to open/close, can cause EPSPs directly or indirectlyHow effective other receptors areInfluence rate of transcription or translation-Can be used to modify a system like for waking or sleeping!! Receptor locations Postsynaptic (most common)PresynapticAutoreceptors: Usually G-protein or inhibitory, negative feedback cuz too much of a NT isnt the best, next AP will release less of the NT--> ONLY bind to the neurotransmitter being released on the axon, e.x: Dopamine neuron will bind to D2 receptorHeteroreceptors: Binds to other neurotransmitters on axon, Dopamine synapse will also have a norepinephrine receptor--> INfluence how much neurotransmitter is released not WHEN, how strong it is. e.x: when we are awake vs asleep "What are the three ways that neurotransmitters can be ""cleaned up""" Why: If there was no clean up then they would keep binding and signal would never end-Diffusion-Enzymatic degredation-Re-uptake Drug types -Agonist: increase function of specific neurotransmitter-Antagonist: Decreases function of specifc neurotransmitter--> BUT that doesnt mean that an agonist will ALWAYS increase brain activity and that an antagonist will decrease brain activity Small-molecule neurotransmitters+ large molecule neurotransmitters SMALL--> co-occurance is the normAmino acids: Glutamate, GABAMonoamines: Catecholamines (Dopamine, ep/norepinephrine), Indolamines (seratonin)Acetylcholine: AcetylcholineLARGE-know very little about this and what they are used for... Glutamate -Primary excitatory neurotransmitter: default, effects are determiend by receptor it binds to which means pos/neg-used throughout the brainIonotropic receptors-AMPAR: binds to glutamate, AMPA receptor, NA+-NMDAR: allows calcium into the cell,, learning and memoryMetabotropic receptors (more recent)-mGLuR 1-8: Not all have excitatory, might inhibit because of negative feedbackNot a great target for drugs because it is too general and pretty much everywhere Drugs: Glutamate (ALL antagonists) -Decreases function of glutamateBarbituates: lethal injection, sedativeNitrus oxide: laughing gasKetamine: blocking NMDAEthanol: AlcoholPattern: they are all reducing activity in the brain, and they cause things with sedation and conciousness-they are not agonists because the brain is pretty much at the maximum of glutamte so increasing the amount of it would cause a panick attack, anxiety, or seziures GABA -Primary inhibitory neurotransmitter, used throughout the brain-Ionotropic and metabotropic receptors--> GABA A: ionotropic, puts chloride inside the cell, more negative---> IPSP-->GABA B: metabotropic, intracellular signals -Again, not a great target for drugs Drugs: GABA (all agonists) Increase function of specifc neurotransmitterbenzos: xanax, ativan, gold standard for removing anxiety--> used for comfort and relaxation, DAMPENS acitivty in brain to reduce anxiety (remember, just cuz agonist, doesnt mean it increases activity in brain)EthanolChloform Ether: gas, not used now, but was for docs in the past to party igPattern: Increase inhibition, anxiety relieving, big dose causes loss in conciousnessWhy not antagonists: similar to glutamate agonist.. would increase anxiety and panick, etc Amines -Dopamine-Ep/norepinphrine-Histamine (allergies)-Serotonin Less targetted to the neuron, more on mass-Almsot all metabotropic-it targets LOTS of the brain at once rather than a specifc area Dopamine (DA) -Originates from 2 nuclei in the tegmentumSubstanta nigraVTA-Projects to some (but not all) brain areas-DA is also made in hypothalamus ---> here it is a hormone-Precursor from diet: tyrosine: amino acid, increase protein-Overlaps with norepinephrine: BOTH are catecholamines-5 DA receptors: D1--> D5 some are +/---> all metabotropic-It is not the pleasure/reward molecule/ Olds and milner study--> motivation for brain stimulation -Dopamine axons project from VTA to Nucleus accumbens (NAcc)*** MAIN TARGET OF DOPAMINE--> put electrodes in rat brain and stimulated the brain for reward by pushing on a lever which they thought made dopamine increase that related to pleasure!-> but this is up to interpretation because you cannot actually talk to rats so how would you know why they kept pressing the lever? Drugs of addiction and dopamine -ALL addictive drugs DIRECTLY (ADHD meds, cocaine, etc) or INDIRECTLY (alcohol) increase dopamine transition ---Amphetamine, cocaine, heroin, nicotine, oxycodone, ethanol, cannaboids, etc etc-BUT there is not much pleasure or euphoria in these drugs, it is more of chasing that high - The use of drugs means you are more likely to to see the drugs.. not for pleasure Dopamine and Parkinsons Disease (PD) -PD is caused by the loss of the substantia nigra (DOPAMINE REMEMBER) pars compacta (SNc)--> it is the loss of these DA neurons -PD is a motor disorder that affects mood because you have this loss off autonomy, and loss of pleasure-L-dopa: is the gold standard for PD treatment, L-dopa will cross the BB barrier and convert it to dopamine --> but this does not increase pleasure it just improves their motor symptoms -other ones: D1 agonist , dopamine receptor, not used anymore because of harmful side effects-Side effects: Large doses of these drugs may cause an increase in types of impulsive behaviour (hyper sexuality, gambling, stealing, etc) what does L-Dopa do for healthy participants? -no effect on mood whatsoever Dopamine and schizophrenia -Schizophrenia medications are dopamine D2R antagonists, they block D2r because there is too much dopamine in the brain---> the more effective the antagonist the more effective it is to treat it-Dopamine theory of schizophrenia: high levels of DA-Individuals with schizophrenia do not have a higher baseline pleasure, their positive symptoms (delusions, hallucinations, disorganzied thoughts/speech) are reduced when taking the D2R antagonists----> so NOT PLEASURE Psychostimulants and dopamine -Psychostimulants act on the monoamine systems, esp. DA, NE, 5-HT--> kinda like monoamine agonists ---> cocaine, crack cocaine, meth, ampthetamine, cathrinones-These drugs cause a wide variety of effects (including euphoria)-But high doses, they can also cause temporary psychosis (at least in acute psychosis)-Not easily distinguished from postive symptoms of schizophrenia Separating pleasure from motivation -Salamone- T maze task--> low effort, low reward vs. high effort, high reward-dopamine Antagonsits--Decrease motivation but NOT pleasure--- can be directly injected or systemichow did they do this?Training: needed to give lots of exposure, block one side and associate it with number of pellets and effortFree choice baseline: wanted to see their preference and most choise the HR optionChoice + DA antagonist: Same drug for schizophrenia, they switched to the easier option... thisis huge because if DA has to do with pleasure then a defict of this you would assume that it would be more likely that they would choose the HR.. LOSS OF MOTIVATIONChoice+ DA antagonist+ no barrier: ALL rats go back to HR.. Dopamine and reward prediction error -Shultz et al.--> pavlovian learningVTA (DA) neuronsFire at first for unexpected reward (grape juice), no light. Increase in dopamine when they recieve an UNexpected good outcomeShift their firing to stimuli that predict reward (Now there is a light and shortly after they receive reward)--> same as aboveGo silent when predicted reward not delivered: Light, but no reward is given.. decrease in dopamine when there is an unexpected bad outcomeCan be chained forward in time Reward prediction error: Better than expected happens means an increase in DA, but when something worse than expected happens there is a decrease in dopamine So what is dopamine for?????? -Importtant for movement-Important for motivation (which is a kind of movement)-Important for learning as related to movement and motivation-important for levels of arousal, attention, executive funciton-NOT PLEASURE Norepinephrine -lvl of arousal -Both and hormone and a neurotransmitter-As NT, it originates in brain stem region called the locus coeruleus- RF NUCLEI, BLUE location-NE projects all over the brain (diff than DA)-Two main receptor types (a1-2, B1-3), with subtypes and sub-subtypes---> ALL metabotropic-NE and ephinphrine act similarly, on same receptors-Causes heterosynaptic facilitation (VIA heteroreceptors--> PRESYNAPTIC)-Baseline levels in wakefulness/arousal - flashbulb memory-Enhancement of memory by stress/emotion--> increase in stress = increase in NE! this is good-Evolutionarily useful PTSD and proprandolol -Propranolol: NE receptor antagonist, beta blocker--> potential PTSD treatment via reconsolidation, delibrately change your memory by telling the experience while propranolol is in your system in order to not have the feelings be as intense and for you to reconsolidate that less intense feeling with a new memory of the traumatic event-recent studys have been trying it on heartbreak  Serotonin -originates from the raphe nuclei (brain stem, RF)-Projects all over brain, esp. cortex, thalamus, and cerebellum-15 receptor types, almost all metabotropic-precursor: tryptophan, diet in food--> passes the BB barrier at the same time as carbs--> so Protein PLUS Carbs means it passes the BB barrier and serotonin occurs(?)-Serotonin depletion effects= remove t and serotonin drops-In stroop task: withold automatic resposne and when 5-HT is depleted it gets worse, and aggresion increases. NO DECREASES IN MOOD SSRIs  "-prozac--> SSRIs block  5-HT transport and causes it to be stuck in the NT syanapse for longer, thus, more binding to the receptors occur because there is more of 5-HT in the synapse-""chemical imbalnce""--> history of monamines implicated in mood disorders, but there is some complications-------> but ofc not only story because of stress, and trauma, etc.. but we just generalized it to a chemical imbalance -lock serotonin from being removed from the synapse-act quick but the imporvements are slow" Diffiusion Diffusion: Float away, not common because it would bind ot other receptors even if you do not want it to-Mainly used when you want a NT to bind to something else Enzymatic degredation "Enzymatic degredation: Found in neuomuscular junctions, they break down NT to metabolites (enzymes) or component parts-As metabolites they can no longer activate a receptor-They were the FIRST discovery of ""clean up""-It is energetically wasteful because if you are breaking down a NT, shortly after you are going to need it again and you hav to build it back up again" Reuptake Recyclying NTs back into the vessicle, this happens in 2 ways-Presynaptic: In the PM, uses PMAT and DAT, Takes these NT from the synapse and it brings it back to the axon (sorta like pumps), then there are these transporters on the vessicle (VMAT) back into the vessicle and once they are in the vessicle they can be reused--MOST common strategy-Astrocytes: they can also help with clean up, they ahve things like DAT, PMAT, also have NET --> NET and DA are similar and they kinda work the same, so some drugs that work on DA also work on NE SSRI efficacy -Original meta-analyses: SSRIs no better than placebo for mild to moderate depression--> publication bias, 75% of OG data was never released to the public -May help with major depression (score over 25), but can be hard to disentangle because of a regression to the mean and the effect size is relatively small-> significantlly alleviated MDD, but very very small-There is a disconnect to what a psychiatrist would take vs. what they would prescribe (most wouldnt take it) Hallucinogens -Psychedelic drugs are serotonin receptor agonists.-Radical changes to our conscious perception and thoughts, minimal effects on mood---> good trip vs bad tripRecent examinations in therapuetic value: end of life care (stress/anxiety reduce), PTSD, addiction, and more---> there can be adverse experience side effectsSerortonin not only mood molecule--> serotonin plays an organzing role and it organzies cortical networks, what we see or find patterns in sensory world Acetylcholine -The first discovered neurotransmitter found in the neuromuscular junctionMotor neurons release into the muscle tissue (has acetylcholine receptors) causes muscles to contract, smooth (gut) and hard musclesAlso in the basal forebrain (less clear about this): Wakefulness, attention, etcNicotine: acetylcholine receptor agonist: activates acetylcholine and is a mild psychostimulant--> in large doses it effects your guts and that is because it is loaded acetylcholine and it activates activating smooth muscle hella Endocannabinoids -Two NTs, receptors (both GPCRs)Molecules binigng to different receptors that are not in the vessicles they are in the dendrites, they are good at crossing the PM Cannot store NT so they are made on demand in dendrites, and when released they spread out to the axon-Travel from dendrite to axon: RETROGRADE transmission--> opposite of normal cuz its usually axon to dendrite-Weaken connection between two cells at the synapse, inhibitory effect fewer NT to be released.---> maybe with delberetly forgetting, weakning your memory-Like PTSD, and some info is more valuable than others-THC in cannabis is a cannabinoid receptor agonist -> this is why heavy cannabis use causes trouble with memory---> CBD is less clear Adenosine -ATP is cellular energy (ATP--> ADP--> AMP)-Adenosine is ATP byproduct -Adenosine receptors: building up across the day, when ur awake adenosine is working up and causes more inhibition, thus why as the day goes on you are more sleeeeepy. Inhibitory in nature, METABOTROPIC-Caffeine/theophylline (Xanthine): With coffee, it binds to adenosine and blocks it, which blocks daytime sleepiness, which makes you more awake---> however, your cells recoginze it's gone, adjusts the system and adds more adenosine, so each week there is more of it and it creates a tolerance-When you wake up you have this coffee withdrawl and when you stop drinking coffee there is LOTS of adenosine in receptors, which causes you to be more sleepy because there is more of that sleepiness in your system Endogenous opioids -AKA endorphins (morphine inside)-giant peptide neurotransmitters-Receptors are all GPCRs -Many NT and receptor types/subtypes-The neurotransmitter systen that exogenous opioids (heroin) mimic: Pain relieving, binding to opiod receptors and activate, gold standard for pain relief --> higher dose or injection: euphoria, addiction, etc-Fentanyl: really strong heroin, causes fatal results-Naloxone: Counteracts effects and is an opiod ANTAgonist -Receptors found in spinal corh, PAG, nucleus accumbens, more---> Motivational systems and euphoria how do we infer the relationship between brain and behaviour? How do we design an experiment pretty uchMost common approaches:Indude a loss of function: more clear, delibertly distruct function (turning down NT)--> if we think a NT is related to a behaviour then we should expect disruptions in behaviourInduce a gain of function: increase in relevant conditions: may cause problems if there is too much increase in NT (seizures), harder to doMonitor behaviour and brain activity simultaneously: brain recording is correlationalEach has considerations and limitations, sometimes a true experiment (true IV) isn't feasible No one ideal method Scales + Trade offs-fMRI takes seconds and captures a lot of action potentials, has goof resolution, and it is across the entire brain-Single electrode: good resolution, time wise better (more neurons), cannot infer whole brain activity What are the three ways we can record the brains electrical activity -single cell recording-EEG-ERP-These are all true direct measures of voltage Single-cell recording -Ideally you would have both: comparing inside vs outside, but it is hard ot perfectly palce them, so usually it is done seperately and you compare one electrode to another electrode-reason that they can be opposite (Pos vs neg.): VOLTAGE is comparison btwn inside and outside of cell***********IntracellularMore rare: in rat/human because it is harder to hit insdie of cell, usually beside the cell (extracellular)Record from inside of cell and it is NEGATIVE (RMP), then when AP it will flip into positiveExtracellularRMP is going to look positive and then when an AP occurs it flips negative- this is opposite to how a normal RMP isGrounding: Flat thing, compare the one electrode to a reletavely nuetral thing-this is a way to tell where your electrode hit the cell (by seeing if the RMP is pos or neg.) What does single cell recording actually mean? -Firing patterns: decoding measurements, making an animal do something a bunch of times and then measure what happens in brain-Raster plots: Sequence is a time point, it is the moment that the subject (i.e rat) presses the lever and you note that, it is stacked and they do it a bunch of times and you have a synchronziation time (time point 0, the moment they press the lever), the ticks are APscan see that they are firing a lot in certain situations/behavioursContext is situation: making sense of what this brain activity means, they fire for a variety of things, no one neurons seems to be firing for a SPECIFIC behaviour, can only make sense if you look at them as a GROUP, many neurons representing a complex thingsPopulation context:many neurons encode complex stimuli, cannot make sense of behaviour in ONE neuron Convergance and divergence We expect to find and do actually find:within the brain we have large popualtions that are encoing popular things (like eyes), as it travels it converges (100 million turns to 50 million), converges and then it keeps condesing each time and once it reaches the specifc part of brain, it diverges and neurons that are specialzed in encoding certain things. -Parrallel processing: sending out signals to multiple places in the brain (above), this is why we are so much better than computers is because of this. Spread out signals everywhere, then diverge it to a specifc thing again-Distributed representations: pretty much population codingBUT--> some data throws things off completely The halle barry neuron "Grandmother cell?-> cannot have a single cell that represents ""grandma"" because if this cell dies, then bye bye-P's had electrodes put in brain (seizure p's), and they showed them pics of stuff and they wanted to see if they found something weird. Put the electrodes in the hippocampus, or adjacent. They had a really low baseline activity, and some neurons ONLY fired when halle berry came up, not some specfic feature of her, it was literally anything that might represent her. CONCEPT cells-Some high convergence in the brain: have some neruons that fire for a specifc stimuli, probably still involved in other population coding" Two main limiations to directly recording electrical activity 1. getting more electrodes into the brain--> multiple recording points on a piece of electrode, but once you start recording this you now need to track a lot of a specifc variable in a specifc space2. making sense of tremendous amounts of data EEG -Measuring from the scalp some limitations:Voltage from brain, you have to go through many layers and it cannot measure deep brain structures, only neurons that are close to the surface (NO SULCI)Waves gave both frequency (measured in Hz) and amplitude EEG waves: brain states? Alpha: awake or excitedBeta: Relaxed,eyes closedGamma: drowsyDelta: Asleep, slower-higher amplitude wavesTheta:-These are NOT thoughts, waves give general state that they are in EEG: sleep has multiple phases Wake: A,G,Bnon rem: T,DREM: A,B- measured with EEG (and emg, eog)-Types of sleep categorized by EEG wave types (f and a) What do the waves mean?? -EEg likely represents PSPs more than APs-Waves show poulation synchorny: millions of neurons firing together Alpha/beta: conscious brain activty?--> wakefulnessTheta ripples: driven by MTL (learning/memory)Delta: was unclear, but maybe sleep? EEG: gamma waves -infromation processing (rlly working on something), attention, maybe consciousness-Meditation: highest amplitude gamma recorded, and gamma changes with skill level!!! -Rhythm likely mediated by fast spiking, GABAergic internerouns (SYNCHRONISITY, not jut inhibitory) ERPs -Averaged response to a stimulus--> more you average the more you can see-subcomponents-waves correlate with certain things, like remembering a word seen over and over again, does not tell us what these waves mean th0p