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1. Historical Foundation of Neuroscience Prehistoric times: Evidence of neurosurgery (trepanation) dates back 7000 years, with individuals drilling holes in skulls to treat conditions like head injuries, epilepsy, and mental disorders. The skulls show signs of healing, indicating the...

1. Historical Foundation of Neuroscience Prehistoric times: Evidence of neurosurgery (trepanation) dates back 7000 years, with individuals drilling holes in skulls to treat conditions like head injuries, epilepsy, and mental disorders. The skulls show signs of healing, indicating the procedures were done on live people. Ancient Egypt (3000 BC): Belief that the heart was the seat of the soul, memory, and consciousness. The first written record of the word "brain" was made here. The Edwin Smith Surgical Papyrus, dated around 1700 BC, is the first known medical document, describing cases related to the brain, meninges, spinal cord, and cerebrospinal fluid. Ancient Greece (300 BC): Hippocrates (460-379 BC) suggested the brain was not only involved in sensation but also in intelligence. Aristotle (384-322 BC) wrongly believed the heart was the seat of the mind, with the brain's role being to cool the passions of the heart. Thales (pre-Socratic philosopher) believed that every event had a natural cause, proposing that the brain produces thoughts (monism). Roman Empire (27 BC-476 AD): Galen (130-200 AD) expanded on Hippocrates' view, linking the brain as the seat of the mind and dissecting animals to identify brain functions. He proposed the cerebrum receives sensations, while the cerebellum controls movement. His work shaped understanding for 1500 years. Renaissance: Leonardo da Vinci provided detailed anatomical drawings and theorized the ventricles as sites for different mental functions (e.g., anterior ventricle for "common sense"). René Descartes (17th century) proposed mind-body dualism, claiming the mind was non-material and interacted with the body through the pineal gland, controlling the flow of "animal spirits" through the brain. Thomas Willis (1621-1675): Known as the father of neurology and the founder of clinical neuroscience, Willis described the Circle of Willis and coined the term "neurology." He linked brain damage to specific behavioral deficits and advanced our understanding of brain functions like perception, cognition, and movement. Franz Joseph Gall (1758-1828): Phrenology: Proposed that different brain areas are responsible for specific functions. He suggested that overuse of certain faculties led to their growth, creating bumps on the skull. His theory was later debunked. Marie-Jean-Pierre Flourens (1794-1867): Aggregate Field Theory: Believed mental functions were distributed across the whole brain, not localized. His experimental brain lesions in animals contributed to the understanding of brain regions responsible for different functions, although he could not pinpoint specific areas for complex functions like memory. Broca’s Area (1861) - Paul Broca: Discovered that damage to the left frontal lobe (Broca's area) led to expressive aphasia (loss of speech production, but intact comprehension).  Wernicke’s Area (1876) - Carl Wernicke: Identified damage to the posterior left hemisphere (Wernicke’s area) as causing receptive aphasia (impaired language comprehension but fluent speech). Conclusion: The brain is the seat of the mind, responsible for mental processes and their behavioral manifestations. While brain functions are localized to specific regions, they work together and interact to produce complex behaviors and cognitive abilities. The study of brain lesions and cellular organization led to the development of cognitive neuroscience as a field. Modern Cognitive Neuroscience: Cognition: Mental processes such as knowing, awareness, perception, and reasoning. Neuroscience: The study of the nervous system and how the brain functions. Cognitive neuroscience emerged in the 1970s to explore how physical brain activity gives rise to the conscious mind. Modern cognitive neuroscience follows Thales’s monistic perspective, which proposes that the conscious mind is a product of the brain's physical activity and is not separate from it. Evidence for this view emerged from studies of brain lesions, where damage to specific areas of the brain caused particular cognitive deficits. Further scientific investigations have confirmed that brain function directly relates to mental processes. OLD EARTH: Life appeared on Earth 4.5 billion years ago, and human brains, in their present form, have existed for only about 100,000 years. The primate brain evolved between 34 and 23 million years ago, with the human lineage diverging from the common ancestor shared with chimpanzees 5 to 7 million years ago. The Anatomy of Language: Language processing involves auditory and visual input and is mainly centered in the left hemisphere. The language processing network is located around the Sylvian fissure. Important areas include Wernicke’s area (posterior temporal lobe) for comprehension, and Broca’s area (frontal lobe) for speech production. Broca’s area (left frontal lobe) is responsible for speech production. Damage to this area causes expressive aphasia (difficulty producing speech). Damage to surrounding areas can also cause  syntax comprehension issues. Wernicke’s area (posterior left hemisphere) is crucial for language comprehension. Damage leads to receptive aphasia (difficulty understanding speech), but patients can speak fluently, though nonsensically. Aphasia: A collective term for language comprehension and production deficits due to neurological damage, which can include speech problems like dysarthria (muscle control issues) and apraxia (motor planning deficits). Anomia: A form of aphasia where individuals cannot name objects, often resulting from strokes. Neuroscience and Social Behavior: Orbitofrontal damage: Leads to socially inappropriate behavior, as demonstrated by Phineas Gage, whose personality changed after a brain injury. Neuroanatomy and Cognitive Function: Brain research progressed after the findings of Broca's area, with neuroanatomists studying the cellular organization of the cortex to understand how specific areas might support certain functions. Korbinian Brodmann (1909) mapped out 52 regions of the cerebral cortex based on cellular differences between brain areas, a study known as cytoarchitectonics. Cognitive Neuroscience Today: Cognitive neuroscience follows Thales’s monistic view, asserting that the conscious mind is a product of the brain’s physical activity. Early evidence came from the study of brain lesions, followed by modern research in cognitive neuroscience, which continues to explore how the brain's physical structure and function give rise to cognition, behavior, and consciousness. Gross Organization of the Nervous System The nervous system can be divided into two main parts: 1. Central Nervous System (CNS): The brain and spinal cord.  2. Peripheral Nervous System (PNS): Nerves and ganglia outside the CNS (the nerves all over the body). Key Terms: 1. Nucleus (plural: Nuclei): A collection/group of neuron cell bodies within the CNS. 2. Ganglion (plural: Ganglia): A group of neuron cell bodies outside the CNS. 3. Tract: A group of nerve fibers (axons) within the CNS. 4. Nerve: A group of nerve fibers (axons) outside the CNS. Cranial and Spinal Nerves Cranial Nerves: There are 12 pairs of cranial nerves that emerge directly from the brain. Spinal Nerves: There are 31 pairs of spinal nerves that emerge from the spinal cord. 1. Central Nervous System (CNS) The cerebral cortex of the brain has millions of neurons arranged in a sheet containing several layers of neurons, folded across the surfaces of the cerebral hemispheres like a handkerchief. The cerebellum also contains billions of neurons and has both gray and white regions. Gray matter in these layers is composed of neuronal cell bodies, whereas white matter consists of axons and glial cells. Axons forming the white matter are grouped together in tracts that run from one cortical region to another within a hemisphere (association tracts), or that run to and from the cerebral cortex to deeper subcortical structures and the spinal cord (projection tracts). Finally, axons may project from one cerebral hemisphere to the other in bundles called commissures. The largest of these interhemispheric projections is the corpus callosum. The brainstem is also a key part of the CNS, connecting the brain to the spinal cord. It controls vital functions like heart rate, breathing, and sleep. The limbic system (including the hippocampus and amygdala) is important for regulating emotions and memory and interacts with the autonomic nervous system, influencing stress responses. 2. Peripheral Nervous System (PNS) The PNS connects the CNS to the body and is responsible for carrying sensory information to the CNS and motor commands from the CNS to muscles and glands. a) Sensory Nervous System: Carries sensory information from sensory organs (such as the skin, eyes, and ears) and internal organs to the CNS. b) Motor Nervous System: Carries motor commands from the CNS to muscles and glands. Are parted into: 1. Somatic Nervous System: Carries information to muscles under voluntary control. 2. Autonomic Nervous System (ANS): Carries messages to internal organs and glands. This system is subdivided into: Sympathetic Nervous System: Controls the body's responses during emergencies, often referred to as the fight or flight response. Parasympathetic Nervous System: Controls the body during non-emergency situations, helping with rest and digestion, often referred to as the rest and digest response. Enteric Nervous System: Controls gastrointestinal behavior and interacts with the CNS. The Spinal Cord and Reflexes The spinal cord extends from the brainstem (around the first spinal vertebra) to the cauda equina and is protected by the vertebral column. It is divided into sections: cervical, thoracic, lumbar, sacral, and coccygeal. Each segment of the spinal cord has right and left spinal nerves that enter and exit the vertebral column through openings called foramina. These nerves carry both sensory and motor axons: The afferent neuron carries sensory input through the dorsal root into the spinal cord. The efferent neuron carries motor output through the ventral root away from the spinal cord. The spinal cord has a central region of gray matter, shaped like a butterfly, with two separate sections or "horns" — the dorsal horn (containing sensory neurons and interneurons) and the ventral horn (containing motor neurons that project to muscles). The dorsal root ganglion (DRG), located just outside the spinal cord, contains the cell bodies of sensory neurons. Autonomic Nervous System (ANS) and Stress The autonomic nervous system (ANS) regulates involuntary bodily functions like heart rate, digestion, and respiratory rate. It is divided into two branches: 1. Sympathetic Nervous System (SNS): This system is responsible for the fight or flight response during emergencies. The SNS mobilizes energy and prepares the body for rapid physical action: Heart rate increases. Blood pressure rises. Breathing rate increases.  Pupil dilation occurs. Sweat production increases. Digestive functions decrease (e.g., slower gastric motility). The primary neurotransmitter used in the sympathetic nervous system is norepinephrine (NE). 2. Parasympathetic Nervous System (PNS): This system is responsible for the rest and digest response, helping the body return to a relaxed state: Heart rate slows. Breathing rate decreases. Digestion increases. Salivation and lacrimation (tear production) increase. The primary neurotransmitter used in the parasympathetic nervous system is acetylcholine (ACh). The vagus nerve, part of the parasympathetic system, plays a major role in regulating the heart, lungs, and digestive tract. Stress Response and Allostasis Homeostasis: Homeostasis refers to a state of equilibrium in the body, where internal conditions are maintained within a narrow, optimal range for survival. Stress: A stressor is anything (external or internal) that moves the body out of homeostasis. The body reacts to stressors with a stress response, which aims to re-establish balance or allostasis. Allostasis refers to the body’s active process of achieving stability through change, especially in response to daily life events. The Stress Response Pathways 1. Sympathetic Stress Response (Fight or Flight): When the body perceives a stressor, the sympathetic nervous system is activated. It rapidly prepares the body for physical action by increasing heart rate, blood pressure, and respiration, and by redirecting blood flow to muscles. At the same time, it suppresses functions like digestion and reproduction. This response is mediated by the release of adrenaline (epinephrine) from the adrenal glands. In males: The stress response often manifests as the “fight or flight” response. In females: The stress response may be more associated with tend and befriend, where individuals seek social support and nurture others in times of stress. 2. HPA Axis Stress Response (Hypothalamic-Pituitary-Adrenal Axis): The second, slower stress response is mediated by the HPA axis: Step 1: The hypothalamus releases Corticotropin-Releasing Factor (CRF). Step 2: CRF triggers the pituitary gland to release Adrenocorticotropic Hormone (ACTH). Step 3: ACTH travels through the bloodstream to the adrenal glands, prompting the release of cortisol (a stress hormone). Step 4: Cortisol acts on various tissues in the body to help mobilize energy reserves and modulate other stress responses. In the brain, cortisol binds to receptors in the hippocampus (which is involved in memory regulation). When the hippocampus detects sufficient cortisol, it sends inhibitory signals back to the hypothalamus, halting further CRF release. This forms a negative feedback loop to regulate stress responses. Long-Term Effects of Stress Chronic stress can have detrimental effects on health, including: Cardiovascular diseases (e.g., hypertension). Compromised immune system, leading to increased susceptibility to infections. Chronic fatigue and adult-onset (Type 2) diabetes. Neuroplastic changes in the brain, particularly in the hippocampus, impairing memory and increasing susceptibility to psychological disorders such as depression and anxiety. Peptic ulcers, inhibition of growth, and reproductive disorders. Chronic pain and shortening of telomeres, contributing to faster biological aging. Yerkes-Dodson Law The Yerkes-Dodson Law explains that optimal performance is associated with an optimal level of arousal. Too little arousal leads to fatigue and underperformance, while too much arousal leads to anxiety and impaired performance. Good stress (eustress) can enhance performance and health in the short term, but bad stress (distress) becomes harmful when prolonged. Layers of the Brain The brain is protected by several layers of tissue: 1. Skin (Scalp) 2. Skull Composed of 22 bones, connected by sutures (fibrous joints). In infants, the skull is not fully fused and contains soft spots (fontanelles) that protect the  brain. 3. Meninges – three membranes that cover the brain: Dura Mater ("hard mother") - the outermost layer. Arachnoid Membrane ("spider") - middle layer, with a subarachnoid space filled with cerebrospinal fluid (CSF). Pia Mater ("gentle mother") - innermost layer, directly covering the brain. Ventricular System Ventricles: Hollow chambers within the brain filled with CSF (Cerebrospinal Fluid). Two lateral ventricles - One in each hemisphere. Third and fourth ventricles CSF is produced by the choroid plexus in the ventricles and serves multiple functions: Buoyancy: Reduces pressure at the brain's base. Protection: Cushions the brain, reducing shock. Nutrient Supply and Waste Clearance Plays a role in the glymphatic system, a waste-clearance pathway linked to the lymphatic system. Impaired CSF flow can lead to hydrocephalus (fluid buildup and brain swelling), which can be treated by draining excess fluid. Blood Supply to the Brain The brain receives about 20% of the body's blood supply, necessary for oxygen and glucose. A constant flow is essential, as the brain can't store glucose or function without oxygen. Disruption of blood flow can lead to unconsciousness or death. Navigating the Brain: Directions Common terms used to describe the brain's anatomy: Dorsal – Toward the back (or superior in the brain). Ventral – Toward the belly (or inferior in the brain). Rostral – Toward the nose (or anterior in the brain). Caudal – Toward the tail (or posterior in the brain). For the brainstem and spinal cord, the directions are slightly tilted, but the same principles apply: Dorsal becomes posterior, and ventral becomes anterior. Additional terms: Medial – Toward the middle of the brain. Lateral – Away from the middle. Bilateral – On both sides. Ipsilateral – On the same side. Contralateral – On the opposite side. Brain Surface Terms Lateral Surface: The outer side of the brain. Medial Surface: The inner middle part of the brain (if the brain were split). Dorsal Surface: The top or superior part of the brain. Ventral Surface: The bottom, exposed when the brain is upside down. Brain Slicing Terminology Axial: Horizontal or transverse slices (top to bottom). Coronal: Vertical slices from front to back. Sagittal: Vertical slices from left to right or vice versa. These directional terms and slicing methods are crucial for imaging the brain, such as during MRI scans. Gross Organization of the Brain Key Parts of the Brain: Cerebrum: Composed of two cerebral hemispheres, responsible for higher cognitive functions. Cerebellum: Coordinates voluntary movements, posture, and balance. Brainstem: Includes the midbrain, pons, and medulla; responsible for basic life functions. Development of the Vertebrate Nervous System 1. Early Development (Neurulation):  Ectoderm, Mesoderm, and Endoderm: Three primary germ layers. Neurulation (Week 3 of Embryonic Development): The neural plate (ectoderm) forms the neural tube, which eventually becomes the central nervous system (CNS). Neural Crest Cells: These cells contribute to the formation of the peripheral nervous system (PNS). 2. Neural Tube Formation: Closure of the Neural Tube: Occurs between days 23-26. Defects: Spina Bifida: Caused by a hole in the posterior end of the tube. Anencephaly: Caused by a hole in the anterior end of the tube. Embryonic Brain Regions Forebrain (Prosencephalon) Midbrain (Mesencephalon) Hindbrain (Rhombencephalon) Adult Brain Regions 1. Forebrain: Cerebral Cortex: Involved in perception, motor action, cognition, and higher mental processes. Basal Ganglia & Limbic System: Associated with motor control, reward processing, emotion, and memory. Diencephalon: Includes the thalamus and hypothalamus. 2. Midbrain: Coordinates eye movements, auditory and visual processing, wakefulness, and some motor functions. 3. Hindbrain: Medulla & Pons: Vital autonomic functions (breathing, heartbeat, blood pressure, etc.) and sensory/motor relay. Cerebellum: Fine motor coordination, posture, balance, and cognitive functions. Lesion Studies: Hindbrain Lesions: Can lead to death if the medulla/pons are damaged. Midbrain Lesions: Results in a coma. Forebrain Lesions: Can result in loss of complex behaviors but still maintain basic functions like walking and eating. Functions of Major Brain Regions Hindbrain: Medulla: Controls basic autonomic functions such as heartbeat, respiration, and digestion. Pons: Connects the brainstem and cerebellum, involved in sleep regulation (REM), and facial movements. Cerebellum: Coordination of movement, balance, motor learning, and cognitive functions. Midbrain: Superior Colliculus: Processes visual information. Inferior Colliculus: Processes auditory information. Pineal Body: Involved in sleep regulation. Red Nucleus: Involved in motor coordination. Forebrain: Cerebral Cortex: Higher cognitive functions like memory, language, perception, and motor actions. Basal Ganglia: Controls motor learning, movement selection, and motivation (reward processing). Limbic System: Processes emotions, motivation, and memory. Basal Ganglia Key nuclei: Caudate nucleus, Putamen, Globus pallidus. Neostriatum (Caudate & Putamen): Involved in voluntary motor actions, motor learning, and routine behaviors. Nucleus Accumbens: Also called ventral striatumPlays a critical role in motivation and reward processing. The basal ganglia are heavily involved in action selection, gating, and motor preparation. Diencephalon: Thalamus & Hypothalamus 1. Thalamus: “Gateway to the Cortex” – relays sensory information to the appropriate cortical areas (except for smell). Contains nuclei that process different types of sensory inputs (visual, auditory, somatosensory). 2. Hypothalamus: Regulates autonomic and endocrine functions (hormones). Controls vital behaviors: Fight, Flight, Feeding, and Mating (the Four F’s). Coordinates circadian rhythms, homeostasis (temperature, metabolic rates, etc.), and links to the pituitary gland. Summary: The brain consists of the cerebrum, cerebellum, and brainstem. The cerebrum is involved in complex cognitive functions and motor control. The brainstem maintains vital life functions, including respiration and heart rate, and connects the brain to the spinal cord. Neurulation and the formation of the neural tube mark the early stages of CNS development. Early defects, such as Spina Bifida and Anencephaly, occur when the neural tube does not close properly. The diencephalon (thalamus and hypothalamus) plays an integral role in sensory relay and homeostasis. The basal ganglia are crucial for motor control and motivation, while the limbic system is involved in emotion and memory. Gross Organization of the Brain (Part 2) Ascending Reticular Activation System (ARAS) A network of neurons involved in regulating sleep-wake cycles and maintaining consciousness. Extends from the medulla through the pons and midbrain to the thalamus and cortex. Controls the level of consciousness (wakefulness), essential for consciousness and arousal of the cortex. Key neurotransmitter systems such as dopaminergic, noradrenergic, serotonergic, and cholinergic pathways mediate its function, supporting both wakefulness and transitions to sleep. Consciousness 1. Contents of Consciousness (Awareness): Involves the cortico-thalamic network  (communication between the thalamus and cortex). 2. Level of Consciousness (Wakefulness): Maintained by brainstem and subcortical structures like the thalamus, hypothalamus, pons, and medulla oblongata. Disorders of Consciousness Coma: No sleep-wake cycles, no awareness, no purposeful behavior. Vegetative State: Sleep-wake cycles present, no awareness, no purposeful behavior. Minimally Conscious State: Sleep-wake cycles present, partial awareness, some purposeful behavior. Locked-In Syndrome: Sleep-wake cycles present, full awareness, limited motor behavior (e.g., eye movements). Measuring Consciousness Electroencephalography (EEG) and BIS value (measures wakefulness). Glasgow Coma Scale: Assesses coma and brain function based on eye, verbal, and motor responses. Metabolic Activity: Brain activity shown via color mapping (warmer colors = more activity). Adrian Owen's Studies: Investigated responses to stimuli (e.g., sounds) in vegetative state patients, showing activation in temporal regions. The studies involves tasks like imagining playing tennis, demonstrating awareness through specific patterns of brain activation. Cerebral Cortex Overview Cortex: The outer layer of the brain, involved in perception, cognition, and voluntary actions. Gyri: Outward folds of the cortex. Sulci: Inward folds of the cortex. Fissures: Deep sulci. Function of Folds: Increase surface area to pack more cortical neurons into the skull, improving communication between neurons. Key Landmarks Central Sulcus: Separates frontal and parietal lobes. Sylvian Fissure (Lateral Sulcus): Separates the temporal lobe from the frontal and parietal lobes. Parieto-occipital Sulcus: Distinguishes the occipital lobe from the parietal and temporal lobes. Hemispheres and Connections Corpus Callosum: Connects the two hemispheres via homotopic (same region) and heterotopic (different regions) fibers. Divided into three parts: genu (anterior), body (middle), and splenium (posterior). Anterior Commissure: Connects the temporal lobes, especially the amygdalae. Posterior Commissure: Smaller, involved in pupillary reflexes. Types of Cortices 1. Neocortex: The youngest and most developed part, with six layers of neurons. 2. Mesocortex: Fewer layers, includes structures like the cingulate gyrus. 3. Allocortex: Older, with three to four layers (e.g., hippocampus). Cell Architecture Grey Matter: Consists of neuron cell bodies and dendrites. White Matter: Contains axons and axon terminals that communicate with other brain regions. Functional Subdivisions of the Cortex 1. Primary Sensory/Motor Cortex: Processes a single modality (e.g., vision, movement). 2. Secondary Sensory/Motor Cortex: Higher-order processing, further elaborating primary sensory information. 3. Association Cortex: Integrates information from different sensory modalities. Sensory and Motor Processing Visual Processing: Information from the eyes goes through the thalamus to the primary visual cortex, then to secondary visual areas for higher processing. Auditory Processing: Sound information travels from the cochlea through the brainstem and thalamus to the primary auditory cortex. Olfactory (Smell): Processes in the olfactory bulb, then to the primary olfactory cortex and orbital frontal cortex. Gustatory (Taste): Processes in the tongue and sends signals to the thalamus and the primary gustatory cortex. Touch (Somatosensory): Sensory receptors in the skin send information through the spinal cord to the thalamus, then to the primary somatosensory cortex. Motor Cortex Motor plans are initiated in the prefrontal and association cortices. The primary motor cortex sends signals through the brainstem to activate specific muscles. Somatotopic Map (Homunculus): A distorted representation of the body in the motor and sensory cortices, with more space allocated to sensitive or finely controlled areas like fingers and lips. Plasticity of the Brain The brain's plasticity allows changes in cortical maps based on experience. Somatosensory Cortex: In the case of a hand amputation, the area of the brain that previously represented the missing fingers gets taken over by the neighboring areas. Phantom Limb Sensation: After amputation, people may still "feel" sensations from a missing limb due to remapping in the somatosensory cortex. Cross-modal Plasticity: Blind individuals who read Braille have enhanced somatosensory  processing in their visual cortex, showing the brain’s ability to repurpose areas for different functions. Motor Cortex: Physical practice (like piano playing) leads to plastic changes, and even imagining practice can induce similar effects on cortical maps. Somatosensory & Motor Cortex Plasticity: Physical or mental practice of sensorimotor skills leads to cortical expansion, showing the brain’s ability to adapt based on experience. The brain can change itself with consistent practice, but this can also lead to issues like phantom limb pain in amputees. Brain-Computer Interfaces (BCI) BCIs allow individuals to control external devices (like robotic arms) by thinking about movements, utilizing motor cortex signals connected to machines. Cerebral Cortex - Gross and Functional Organization Hippocampus Named after its resemblance to a "seahorse" (Greek: hippokampus), the hippocampus is bilaterally located in the medial temporal cortex, one in each hemisphere. Function: Critical for forming new declarative long-term memories, including: Episodic Memory: Personal events. Semantic Memory: Facts and world knowledge. Damage: Anterograde Amnesia: Inability to form new declarative memories. Retrograde Amnesia: Loss of past memories (less common). Vulnerability: Chronic stress can cause hippocampal atrophy, linked to smaller hippocampal volume in depression (19% smaller left hippocampus) and PTSD (8% smaller right hippocampus). This leads to memory problems. Neurogenesis: One of the few brain areas where new neurons grow in adulthood. Exercise and antidepressants can enhance hippocampal neurogenesis, contributing to improved plasticity and  larger hippocampal volume. Interesting Case: London taxi drivers exhibit increased hippocampal grey matter, especially in the right hemisphere, due to navigation demands, unlike bus drivers. Amygdala A subcortical structure near the hippocampus in the medial temporal lobe. Function: Involved in emotional processing, especially fear. Effects of Stress: Opposite to the hippocampus, chronic stress increases synaptic connections and dendritic structures in the amygdala, potentially contributing to anxiety disorders. Size and Function: Smaller amygdalae result in reduced ability to experience or recognize fear. Hyperactivity in the amygdala is linked to anxiety disorders. Brain Lobes and Functions 1. Occipital Lobe: Processes visual information (visual cortex). 2. Parietal Lobe: Handles somatosensory and spatial information, body representation, and sensory integration. 3. Temporal Lobe: Processes auditory information, language comprehension, and memory (hippocampus). 4. Frontal Lobe: Planning and executing movements (motor cortex). Social behavior, emotional regulation, language production, and overall brain control. Cerebral Hemispheres Each hemisphere controls and processes information for the contralateral body side. Functional asymmetry exists: Left Hemisphere: Dominant for language and verbal skills. Right Hemisphere: Specializes in spatial skills. Split-Brain Studies: Split-brain patients (e.g., W.J., who underwent a corpus callosotomy) demonstrate independent functioning of hemispheres. Visual Input: Items shown to the right visual field (processed by the left hemisphere) can be verbally identified. Items shown to the left visual field (processed by the right hemisphere) cannot be verbalized but can guide left-hand actions. Structural Differences: The right hemisphere protrudes more in the front, while the left protrudes in the back. The Sylvian fissure has a steeper upward curl in the right hemisphere. Corpus Callosum:  The splenium (posterior portion) is critical for interhemispheric transfer of visual, tactile, and auditory information. Severing the posterior callosum disrupts these transfers, emphasizing the need for meticulous methodological approaches in studying split-brain patients. Summary of Notes: Blood Supply, Stroke, Neuroplasticity, and Development Brain’s Blood Supply The brain uses 20% of oxygen and 40% of glucose in the body due to its high metabolic demands despite being only 2% of body weight. Blood is supplied via four main arteries: 1. Two internal carotid arteries (anterior circulation – forebrain) 2. Two vertebral arteries (posterior circulation – cerebellum, brainstem, parts of the forebrain) The Circle of Willis, formed by the basilar and internal carotid arteries, provides a safety mechanism to ensure blood supply even if one artery is blocked. The anterior, middle, and posterior cerebral arteries supply specific parts of the brain: 1. Anterior: Medial/anterior cortex 2. Middle: Lateral surface 3. Posterior: Medial/posterior cortex Stroke (Cerebrovascular Accident) Definition: Death of neurons due to insufficient blood flow, typically caused by: Blockage (atherosclerosis, thrombosis) Bleeding (hemorrhagic stroke) Risk factors: Chronic stress, high blood pressure, obesity, smoking, diabetes, and abnormal cholesterol levels. Stroke results in neuronal death within minutes, with outcomes dependent on the artery affected. Stroke Recovery and Constraint-Induced Movement Therapy (CIMT) Developed by Edward Taub based on research with Silver Spring monkeys, which demonstrated "learned non-use" of affected limbs after sensory nerve damage. CIMT Principles: Restrain the unaffected limb (90% of waking hours). Practice functionally relevant tasks with the affected limb. Use “shaping” (incremental difficulty) and “massed practice” (intense daily training). Outcomes: Encourages compensatory pathways and restores some functionality even years after stroke. Brain Stimulation for Stroke Recovery Non-invasive methods (e.g., TMS and tDCS) enhance recovery by: Increasing activity in damaged brain areas. Decreasing overactive inhibitory signals from the unaffected hemisphere. Brain-Machine Interfaces (BMI) BMIs use neural signals to control prosthetics or robotic devices, offering rehabilitation for severe motor impairments (e.g., spinal cord injury). Current challenges: Stable, long-term control systems. Integration of sensory feedback ("closed-loop" systems). Advancements: Neural plasticity allows the brain to adapt its activity to control devices without pre-training. Development of the Brain 1. Synaptogenesis and Pruning: Synapse formation begins in utero (~week 27) and peaks after birth. Synaptic pruning refines neural connections, removing redundant pathways during early development. 2. Critical Periods:  Sensory systems require input during early life to optimize neural representations (e.g., vision, hearing). 3. Plasticity and Sensory Loss: Cross-modal plasticity: Sensory loss (e.g., blindness or deafness) leads to cortical reorganization, enhancing other sensory modalities. Limbic and Paralimbic Areas Limbic areas (e.g., hippocampus, amygdala) integrate visceral and emotional states with cognition. Paralimbic areas (e.g., cingulate gyrus, insula) link emotional states to behavior and cognition. FAST for Stroke Detection Face drooping Arm weakness Speech difficulty Time is critical: Seek medical help immediately. MICRO Cells of the Nervous System 6.1.1 Structure of Neurons To understand the mind, we must study the brain at the cellular level—starting with neurons. The discovery that the brain is composed of cells aligns with the cell theory (1839), which remains foundational to modern biology. Brodmann and others used stains like those developed by Franz Nissl to examine differences in cell types across brain regions, a field called cytoarchitectonics. They showed that structurally distinct areas often serve distinct functions. However, it was the work of Camillo Golgi and Santiago Ramón y Cajal that revolutionized our understanding of the nervous system. Key Contributions: Golgi and Cajal 1. Camillo Golgi (1843–1926) Invented the Golgi method (1873): immersed brain tissue in potassium dichromate and silver nitrate, selectively staining 1–10% of neurons to reveal their full structure. Described the brain as a syncytium, a continuous network of fused cells. 2. Santiago Ramón y Cajal (1852–1934) Improved the Golgi method, creating deeper stains and enabling detailed study. He discovered that neurons are discrete entities separated by small gaps, laying the foundation for the neuron doctrine. Known as the "father of modern neuroscience" for establishing that the brain and nervous system consist of individual cells. Both received the 1906 Nobel Prize in Physiology or Medicine for their work, though Golgi never accepted the neuron doctrine. The Neuron Doctrine This foundational theory asserts: 1. The neuron is the basic structural and functional unit of the nervous system. 2. Neurons are discrete cells, not continuous networks. 3. A neuron has three parts: dendrites, axon, and cell body. 4. Information flows in one direction: dendrites → cell body → axon. Modern advances, like using green fluorescent proteins from jellyfish, allow us to visualize neurons in living or fixed tissue. Structure of a Neuron Neurons consist of: 1. Soma (Cell Body) Houses the nucleus (containing DNA for transcription into RNA) and organelles like the rough endoplasmic reticulum (site of protein synthesis). Proteins are packaged in the Golgi apparatus and transported via vesicles. 2. Extensions (Neurites) Dendrites: Receive information from other cells; often have dendritic spines that form synaptic connections. Axon: Sends information; may branch into axon collaterals and terminate in axon terminals at synapses. 3. Cytoskeleton Composed of microtubules, neurofilaments, and microfilaments, maintaining neuron shape and enabling intracellular transport. Myelin sheaths, produced by glial cells, insulate some axons, increasing the speed of signal transmission. White matter contains myelinated axons, while gray matter includes cell bodies and dendrites. Neuron Function and Communication Neurons specialize in: 1. Receiving signals via dendrites. 2. Integrating and processing signals in the soma. 3. Transmitting signals through the axon to other neurons or effector cells. Neurons form complex networks: Microcircuits: Process specific tasks like sensory input or motor control. Macrocircuits: Long-distance connections for global brain function. Classification of Neurons 1. Structural Types Unipolar: One process (e.g., invertebrate nervous systems). Bipolar: Two processes; common in sensory neurons. Pseudo-unipolar: Fused processes; found in somatosensory neurons. Multipolar: Many dendrites, one axon; most common type. 2. Functional Types Sensory (Afferent): Carry signals to the brain or spinal cord. Motor (Efferent): Carry signals to muscles and glands. Interneurons: Connect neurons within the CNS. Neural Circuits and Reflexes Example: Knee-jerk reflex 1. Stretch receptors detect muscle stretch. 2. Sensory neurons send signals to the spinal cord. 3. Motor neurons contract the quadriceps while inhibiting opposing muscles. Neuronal Cytoskeleton and Alzheimer's Disease Alois Alzheimer (1901) identified neurofibrillary tangles and amyloid plaques as hallmarks of Alzheimer’s disease: 1. Neurofibrillary tangles: Formed by clumped tau proteins after microtubule disintegration. 2. Amyloid plaques: Toxic clumps of beta-amyloid protein. These changes lead to widespread neuron death, starting in the hippocampus (memory loss) and spreading to other brain regions. Additional Notes Broca and Wernicke's areas communicate via the arcuate fasciculus, enabling both language comprehension and production. Neurons in large brains optimize connectivity by balancing short local connections for efficiency with a few long connections for global communication. Glial Cells: The Unsung Heroes of the Brain Glial cells, often referred to as the "glue" of the nervous system, provide essential support and contribute to brain function. The term "glia" comes from the Greek word for "glue," as they support and maintain the nervous system. These cells were first identified by Rudolph Virchow in 1866, and their full functions have remained a topic of research, with significant contributions from scientists like Santiago Ramón y Cajal. Role of Glia in Brain Function Rudolph Virchow (1866) highlighted the importance of glial cells in the structure of the nervous system, describing them as the "substance" that holds neurons together. Santiago Ramón y Cajal questioned the function of glial cells, noting the mystery that still surrounds their exact role in the nervous system. Einstein’s Brain Study (1980s): Research by Marian C. Diamond on Einstein's brain revealed a higher ratio of glial cells compared to neurons, particularly in Brodmann areas 9 and 39,  suggesting that glial cells might play a role in cognitive abilities like those observed in Einstein. Types of Glial Cells There are several types of glial cells in the central nervous system (CNS) and peripheral nervous system (PNS): 1. Astrocytes: Star-shaped cells that provide structural support. Form the Blood-Brain Barrier (BBB), which regulates the entry of substances into the brain. May regulate blood flow and modulate neuronal activity. Help supply glucose and neurotransmitter precursors. Act in injury response by forming scars. 2. Oligodendrocytes: Form the myelin sheath around axons in the CNS, which speeds up electrical signal transmission. Myelin damage leads to diseases like Multiple Sclerosis (MS), which disrupts nerve signal conduction. 3. Microglia: Small immune cells that act as the CNS’s primary defense. They identify and eliminate damaged neurons, plaques, or pathogens. Can contribute to neuroinflammation, as seen in Alzheimer’s disease, where they attack both plaques and healthy neurons. 4. Ependymal Cells: Line the brain’s ventricles and spinal cord, playing a role in cerebrospinal fluid production. 5. Schwann Cells (in PNS): Provide myelin for peripheral nerves, enabling faster transmission. Unlike oligodendrocytes, Schwann cells myelinate one axon at a time. Schwann cells aid in nerve regeneration in the PNS, unlike the CNS where regeneration is limited. Multiple Sclerosis (MS) MS is an autoimmune disorder where the immune system attacks myelin, leading to neurological damage. Symptoms vary but can include motor, visual, cognitive, and sensory issues. Types of MS: Relapsing-remitting MS: Symptoms come and go but progressively worsen over time. Primary progressive MS: Gradual worsening without remissions. Secondary progressive MS: Initially relapsing-remitting, then progresses steadily. Regenerative Potential of Glial Cells Glial cells, especially Olfactory Ensheathing Cells (OECs), have regenerative properties. Olfactory Ensheathing Cells surround olfactory sensory axons and support the growth of new neurons. OECs have shown promise in spinal cord injury research. A study involving paraplegic patients showed that transplantation of these cells was safe and feasible, with no deterioration in neurological function over three years. Conclusion Glial cells are vital for maintaining the structure and function of the nervous system. While much of their role remains under investigation, they are clearly integral to neuronal support, immune defense, myelination, and even regeneration. Their unique regenerative properties, especially in the peripheral nervous system and olfactory regions, offer exciting possibilities for future therapies in neurodegenerative diseases and spinal cord injuries. Neuronal communication within neurons Neuronal Communication: Electrical and Chemical Signals The signal within neurons is electrical, meaning that ions move across membranes to generate electrical potentials. Communication between neurons is chemical, occurring at synapses, where neurotransmitters transmit signals from one cell to another. Principles of Electrical Signals in Neurons Electrical current is the flow of charged particles, which are ions in biological systems (not electrons like in wires). Important ions in neuronal signaling: K+ (potassium, positively charged)  Na+ (sodium, positively charged) Cl- (chloride, negatively charged) Ca²+ (calcium, positively charged) Diffusion and Concentration Gradients Diffusion is the movement of molecules from areas of high concentration to low concentration until equilibrium is reached. A concentration gradient refers to the difference in concentration between two regions. For example, when salt dissolves in water, it creates a higher concentration of Na+ and Cl- where it dissolves. These ions will diffuse to balance out the concentration. Ion Movement and Electrochemical Gradients Ions like Na+, K+, Cl-, and Ca²+ move across the neuron membrane according to both their concentration gradients (from high to low concentration) and their electrical gradients (opposite charges attract, and like charges repel). The combined force of these two gradients is the electrochemical gradient, which dictates the direction of ion movement. Neuronal Membrane and Resting Potential The neuronal membrane is a lipid bilayer that separates the intracellular fluid (inside the neuron) from the extracellular fluid (outside the neuron). It regulates the flow of ions through channels and pumps. The membrane is selectively permeable to different ions, which helps establish the resting membrane potential. At rest, the neuron has: More Na+ and Cl- outside the neuron. More K+ and negatively charged proteins (A-) inside the neuron. This results in a resting membrane potential of about -70 mV, meaning the inside of the neuron is more negative compared to the outside. The sodium-potassium pump (Na+/K+ ATPase) is key in maintaining this resting potential by pumping 3 Na+ out and 2 K+ in against their concentration gradients, consuming ATP in the process. Generation of Action Potentials When a neuron receives a stimulus, Na+ channels open, allowing Na+ to flow into the neuron and depolarize it (make it less negative). A graded potential refers to a small, local change in membrane potential. If this depolarization reaches a critical threshold, typically around -55 mV, an action potential is triggered. During the action potential:  Na+ channels open, allowing Na+ to rush in, causing rapid depolarization and pushing the membrane potential toward +30 mV. This is an all-or-nothing response, meaning that once the threshold is reached, the action potential is always the same size. After depolarization: Na+ channels close and K+ channels open, allowing K+ to flow out, leading to repolarization, which returns the membrane potential toward the resting state. Sometimes K+ channels remain open too long, causing hyperpolarization (the membrane potential becomes more negative than at rest). This is followed by a relative refractory period, where a stronger stimulus is needed to trigger another action potential. During the absolute refractory period, Na+ channels are inactivated, and the neuron cannot fire another action potential until it recovers. Propagation of Action Potentials Saltatory conduction occurs in myelinated axons, where the action potential jumps between the nodes of Ranvier, speeding up signal transmission. In unmyelinated axons, the action potential propagates more slowly as the entire axon must be depolarized along its length. Synaptic Transmission At synapses, presynaptic neurons release neurotransmitters that bind to receptors on postsynaptic neurons, transmitting the signal across the synaptic cleft. Neurons act as both presynaptic and postsynaptic depending on whether they are sending or receiving the signal. Ion Channels and Permeability Ion channels are proteins embedded in the membrane that allow ions to pass through. They can be gated (opened or closed in response to stimuli) or non-gated (always open). The permeability of the membrane to specific ions influences how easily they can cross, which in turn affects the membrane potential and the generation of action potentials. Summary Neuronal communication relies on the movement of ions across membranes, generating electrical signals. The resting membrane potential is maintained by ion pumps and selective permeability. When a neuron is sufficiently depolarized, an action potential is triggered, which propagates down the axon to communicate with other neurons. This process involves voltage-gated ion channels, myelination, and synaptic transmission. Neuronal Communication between Neurons Neuronal communication is fundamental to brain function, relying on electrical impulses (action potentials) within neurons and chemical signaling between them. Key Historical Insights: Neurons are independent cells, not a continuous network. This was understood by the late 19th century and supported by scientists like Santiago Ramón y Cajal and Sigmund Freud. The question of how neurons communicate arose with the discovery that the brain consists of individual cells generating electrical signals. Discovery of Synapses: Charles Scott Sherrington (1932 Nobel Prize) is credited with discovering synapses. His investigation of reflexes (e.g., the knee-jerk reflex) revealed that sensory neurons caused increased activity in motor neurons, but the reverse did not occur. This suggested one-way communication, indicating that some form of connection between neurons (likely involving chemicals) was at play. Synapse Structure: The synapse is the specialized junction where one neuron communicates with another. It consists of: Presynaptic neuron (sends signals), Synaptic cleft (gap between neurons, ~20-40 nanometers wide), Postsynaptic neuron (receives signals), typically on a dendritic spine or sometimes on the soma or an organ. Chemical Transmission of Nerve Impulses: Otto Loewi (1936 Nobel Prize) demonstrated chemical communication between neurons. His famous experiment involved frog hearts: when he stimulated the vagus nerve of one heart, it slowed, and this effect was transmitted via fluid to the other heart, showing that a chemical (later identified as acetylcholine) was involved. Neurotransmission: Neurotransmission refers to communication between neurons. Electrical signals travel within neurons, while chemical signals (neurotransmitters) are used for communication between them. Neurotransmitters are chemicals released by neurons at synapses that affect other cells (neurons or effector organs). They can be excitatory (e.g., glutamate) or inhibitory (e.g., GABA). Neurotransmitter Synthesis and Release Process: 1. Synthesis: Neurotransmitter molecules are synthesized from precursors inside the neuron. This occurs either in the cell body (for larger molecules) or in the axon terminal (for smaller molecules). These precursors come from nutrients and are transported with the help of special transporters and enzymes. 2. Storage: Neurotransmitters are stored in vesicles. If not stored, they are broken down by degrading enzymes. 3. Release: When the neuron is activated (via an action potential), vesicles fuse with the presynaptic membrane, releasing neurotransmitters into the synapse via exocytosis. This is triggered by the influx of Ca²+ ions after the membrane depolarization. 4. Binding: Neurotransmitters bind to receptors on the postsynaptic neuron. These receptors can be: Ionotropic receptors (ligand-gated ion channels, causing rapid effects like depolarization or hyperpolarization). Metabotropic receptors (indirectly affecting ion channels through intracellular signaling). 5. Autoreceptors: Some neurotransmitter molecules also bind to autoreceptors on the presynaptic neuron, which acts as a negative feedback mechanism, inhibiting further neurotransmitter release.  6. Deactivation: Neurotransmitters must be quickly deactivated to ensure proper signal transmission. This can occur through: Reuptake: Neurotransmitters are transported back into the presynaptic neuron via transporters. Enzymatic degradation: Enzymes break down neurotransmitters in the synaptic cleft. Diffusion: Neurotransmitters diffuse away from the synapse, possibly being absorbed by glial cells. Electrical Synapses: Gap junctions allow for direct, bidirectional electrical communication between cells. These are faster but less flexible than chemical synapses. They are used for reflexes and synchronization in some areas of the brain (e.g., retina, thalamus, hippocampus). Electrical synapses do not amplify signals, unlike chemical synapses, and are less plastic. Types of Neurotransmitters: 1. Small Molecule Neurotransmitters: Amino acids: Glutamate (excitatory, major neurotransmitter in the brain), GABA (inhibitory, regulates anxiety and muscle tone), Glycine, Aspartate. Monoamines: Dopamine, Norepinephrine, Epinephrine, Serotonin, Histamine. Cholinergics: Acetylcholine (important for parasympathetic functions and muscle contraction). 2. Large Molecule Neurotransmitters: Neuropeptides: Opioids (endorphins, enkephalins), Hypothalamic releasing hormones, Neurohypophyseal hormones (oxytocin, vasopressin), Corticotropin-releasing factor. Endocannabinoids: Anandamide. Neurotransmitter Functions: Excitatory neurotransmitters: These stimulate the postsynaptic neuron, causing depolarization and the potential firing of an action potential. Examples: glutamate, acetylcholine (in some cases), dopamine, serotonin. Inhibitory neurotransmitters: These inhibit the postsynaptic neuron, causing hyperpolarization and reducing the likelihood of firing an action potential. Examples: GABA,  glycine. Neuromodulators: The non-amino acid neurotransmitters (monoamines, neuropeptides) act as neuromodulators, influencing the activity of neurotransmitter systems and modulating specific brain functions. Neurotransmitter Criteria: For a substance to be classified as a neurotransmitter, it must meet these criteria: 1. The chemical must be produced and found in the neuron. 2. It must be released upon neuron activation. 3. The chemical must bind to postsynaptic receptors and induce a biological effect. 4. It must be inactivated after release (via reuptake, enzymatic breakdown, or diffusion). 5. If artificially applied, it should replicate the same effect as endogenous release. Neurotransmitter Systems: Some neurons produce only one type of neurotransmitter, while others produce multiple types. These neurons form distinct systems (e.g., cholinergic system, dopaminergic system, serotonergic system). Excitatory neurotransmitters include acetylcholine, catecholamines (dopamine, norepinephrine), glutamate, histamine, serotonin, and some neuropeptides. Inhibitory neurotransmitters include GABA, glycine, and certain neuropeptides. Neuronal Communication Between Neurons 2 Dopamine Neurotransmission: Dopamine Synthesis: Dopamine is synthesized from the amino acid tyrosine via a series of enzymatic steps. L-DOPA is an intermediate compound, eventually forming dopamine (DA). Dopamine is a small molecule neurotransmitter, made locally in the axon terminal and stored in vesicles using a Vesicular Monoamine Transporter (VMAT). Neurotransmitter Release: An action potential triggers the opening of voltage-gated calcium channels in the axon terminal, leading to calcium influx. This causes neurotransmitter-filled vesicles to fuse with the presynaptic membrane, releasing dopamine into the synaptic cleft. Dopamine binds to specific receptors on the postsynaptic neuron, which can either excite or inhibit the postsynaptic cell, depending on the receptor subtype. Neurotransmitter Clearance: Dopamine is removed from the synaptic cleft via Dopamine Transporters (DAT), which recycle it back into the presynaptic terminal. Once inside, dopamine can either be repackaged into vesicles or broken down by MAO (Monoamine Oxidase) and COMT (Catechol-O-Methyltransferase). Dopamine Pathways: 1. Mesostriatal Pathway: Substantia Nigra → Striatum (caudate and putamen). Involved in voluntary movement regulation and the basal ganglia, which modulates movement. 2. Mesolimbocortical Pathway: Ventral Tegmental Area (VTA) → Nucleus Accumbens, Cortex, Hippocampus. Often split into: Mesolimbic Pathway: Involves the ventral striatum and is related to reward and reinforcement. Mesocortical Pathway: Leads to the prefrontal cortex and hippocampus, contributing to executive functions and emotional regulation. Dopamine in Hypothalamus also plays a role in various functions. Dopamine-Related Illnesses: Parkinson’s Disease: A neurodegenerative disorder, primarily affecting the mesostriatal pathway (Nigrostriatal pathway). It involves the degeneration of dopamine-producing neurons in the substantia nigra, leading to motor symptoms such as: Tremors (resting tremor) Rigidity Bradykinesia (slowness of movement) Postural instability and balance issues Treatment: Levodopa (L-DOPA): A dopamine precursor that temporarily alleviates symptoms. Deep Brain Stimulation (DBS): Involves implanting electrodes in regions like the Subthalamic Nucleus, which modulates basal ganglia function. Encephalitis Lethargica (Sleeping Sickness): Characterized by Parkinson’s-like symptoms, including motor issues and lethargy. Some patients responded to L-DOPA therapy, suggesting similar underlying dopamine dysfunction. Addiction and Dopamine: Mesolimbic Pathway (Reward Pathway):  Dopamine plays a key role in reward and motivation, affecting behaviors like gambling, gaming, and drug addiction (e.g., cocaine, amphetamines). Addiction: Driven by the motivation (WANTING) rather than the pleasure (LIKING) of rewards. Wanting is associated with dopamine, while liking is related to opioids (endorphins). Cocaine and Amphetamines increase dopamine in the synaptic cleft by blocking dopamine reuptake, leading to heightened dopamine signaling. Chronic use leads to tolerance (reduced receptor availability) and neurotoxicity (damage to dopaminergic neurons). Methamphetamine: Unlike cocaine, meth enters presynaptic neurons and displaces dopamine from vesicles, also inhibiting MAO (Monoamine Oxidase) activity. This leads to neurotoxic effects and long-term cognitive impairments. Addiction Mechanism: Repeated drug use leads to neuroplastic changes in the brain’s reward circuitry, with a disconnection between wanting and liking, contributing to compulsive behaviors. Gaming and Internet Addiction: Similar brain mechanisms (dopamine release) contribute to compulsive behavior and can lead to addiction. Dopamine + Disorders ADHD and Dopamine: ADHD: Associated with reduced dopamine transmission in the prefrontal cortex, affecting attention and impulse control. Treatment often involves stimulants like methylphenidate and amphetamine, which increase dopamine levels in the prefrontal cortex, improving symptoms. Schizophrenia and Dopamine: Schizophrenia: A psychiatric disorder marked by delusions, hallucinations, and cognitive impairments. Dopamine Hypothesis: Suggests that excessive dopamine activity in subcortical structures (e.g., mesolimbic pathway) contributes to positive symptoms (delusions, hallucinations), while deficient dopamine activity in the prefrontal cortex leads to negative symptoms (cognitive deficits). Antipsychotic Medications: Block dopamine receptors, reducing transmission and alleviating psychotic symptoms. Huntington’s Disease: A hereditary neurodegenerative disorder involving hyperkinesia (excessive movement). Caused by disruptions in basal ganglia signaling, leading to increased inhibition of basal  ganglia output, resulting in excessive movement. Psychoactive Drugs & Their Mechanisms: Psychoactive drugs affect the CNS, altering mood, thought, or behavior, and can be used recreationally or to manage mental health. These drugs can cause substance abuse. Mechanism of Drugs: Agonistic Drugs: Increase or mimic neurotransmitter effects. Antagonistic Drugs: Block or decrease neurotransmitter effects. Major Neurotransmitters and Their Effects: 1. Dopamine: Related to Parkinson’s disease, schizophrenia, bipolar disorder, ADHD, and drug abuse. L-Dopa used for Parkinson’s treatment. Bipolar disorder involves extreme mood swings, treated similarly to schizophrenia. 2. Glutamate: The main excitatory neurotransmitter, important for learning and memory. Glutamate hypothesis of schizophrenia: Suggests schizophrenia is related to glutamate dysfunction rather than dopamine. Alcohol and ketamine are antagonists of glutamate, blocking its receptors. 3. GABA: The most common inhibitory neurotransmitter, involved in anxiety, epilepsy, and impulse control. Alcohol, benzodiazepines, and barbiturates are GABA agonists, enhancing its effects. Alcohol blocks glutamate (antagonist) and enhances GABA (agonist), leading to  depressant effects. Alcohol also indirectly increases dopamine release by inhibiting GABAergic cells. 4. Norepinephrine (Noradrenaline): Involved in stress response, alertness, and sleep/wake cycles. Disorders: anxiety, PTSD, ADHD, depression. Drugs: Beta-blockers treat anxiety by blocking norepinephrine receptors. Psychostimulants (e.g., methylphenidate) treat ADHD and depression by enhancing norepinephrine. 5. Serotonin: Regulates mood, appetite, sleep, and arousal. Disorders: depression, anxiety. Drugs: SSRIs, MAOIs, and ecstasy (MDMA) are serotonin agonists. MDMA releases serotonin and blocks reuptake, increasing serotonin in the synapse. 6. Acetylcholine (Ach): Involved in muscle activation, attention, and memory. Related diseases: Alzheimer’s (low acetylcholine). Nicotine is an acetylcholine agonist, enhancing its effects and leading to dopamine release. Botox inhibits acetylcholine release, causing muscle paralysis. 7. Endogenous Opioids (Endorphins): Involved in pain suppression, euphoria, and relaxation. Drugs: morphine and heroin are opioids that bind to opioid receptors, inducing euphoria. They also indirectly increase dopamine, contributing to addiction. 8. Endocannabinoids: Involved in pain relief, euphoria, and relaxation. Cannabis is an agonist of cannabinoid receptors, inhibiting GABA, and increasing dopamine release. 9. Oxytocin: A neurotransmitter and hormone involved in social bonding, stress reduction, and mood regulation. Disorders: autism (possible link). MDMA also increases oxytocin, contributing to bonding effects. 10.Caffeine: An adenosine receptor antagonist: Prevents adenosine from binding to its receptors, blocking the feeling of sleepiness and increasing neural activity.