Module 2 | Source: A Brain-Mind Odyssey, UC Berkeley, Ch. 7
Tags: neuroanatomy, CNS, PNS, autonomic nervous system, sympathetic, parasympathetic, cranial nerves, neuromuscular junction, neurotransmitter systems, dopamine, serotonin, norepinephrine, acetylcholine, agonist, antagonist, seizure, epilepsy, excitotoxicity, raphe nuclei, locus coeruleus, substantia nigra, ventral tegmentum
The nervous system divides into the CNS (brain and spinal cord) and PNS (everything else, including 12 pairs of cranial nerves and the autonomic system). The autonomic nervous system splits into sympathetic ("fight or flight," using norepinephrine) and parasympathetic ("rest and digest," using acetylcholine). Major neurotransmitter systems, each originating from small brainstem nuclei, modulate the entire brain. When the balance of excitation and inhibition breaks down, the result can be seizures or excitotoxic cell death.
Neuromuscular junction
The synapse between a motor neuron and a skeletal muscle fibre. Uses ionotropic acetylcholine receptors (AChRs).
CNS (central nervous system)
The brain and spinal cord.
PNS (peripheral nervous system)
All neural networks outside the brain and spinal cord, including sensory systems of the head and their connections to the brain.
Cranial nerves
Twelve pairs of nerves that connect the CNS directly to structures of the head and body (rather than going through the spinal cord).
Autonomic nervous system
A division of the PNS that regulates internal organs and involuntary functions: heart rate, blood pressure, respiration, digestion.
Sympathetic nervous system
The "fight or flight" branch of the autonomic system. Uses norepinephrine as the neurotransmitter at target tissue connections. Effects include increased heart rate, dilated airways, dilated pupils, inhibited salivation.
Parasympathetic nervous system
The "rest and digest" branch. Uses acetylcholine at target tissue connections. Effects include decreased heart rate, constricted airways, constricted pupils, stimulated salivation.
Sympathomimetic
Any drug or action that stimulates the sympathetic nervous system.
Sympatholytic
Any drug that decreases the effects of the sympathetic nervous system on target organs.
Parasympathomimetic
Any drug or action that stimulates the parasympathetic nervous system.
Parasympatholytic
Any drug that decreases the effects of the parasympathetic nervous system on target organs.
Agonist
A molecule that binds to a receptor and activates it. A neurotransmitter is an agonist at its own receptor.
Antagonist
A molecule that binds to a receptor and blocks the action of the neurotransmitter at that receptor, without activating it.
Acetylcholinesterase
The enzyme that rapidly cleaves acetylcholine into acetate and choline after release at axon terminals.
Choline acetyltransferase
The enzyme that synthesises acetylcholine.
Serotonin (5-HT, 5-hydroxytryptamine)
A neurotransmitter biosynthesised in two steps from the amino acid tryptophan (first by tryptophan hydroxylase, then by aromatic amino-acid decarboxylase). Also found in blood, where it affects blood vessel constriction and dilation.
Raphe nuclei
Clusters of serotonergic neurons located along the midline of the brainstem. Their axons innervate the entire brain.
Dopamine
A neurotransmitter produced by small clusters of neurons deep in the brain. Key nuclei include the substantia nigra and the ventral tegmentum.
Substantia nigra
A dopaminergic nucleus in the brainstem. Degeneration here is associated with Parkinson's disease.
Ventral tegmentum (VTA)
A dopaminergic nucleus in the brainstem. Also contains GABA-producing cells.
Norepinephrine (noradrenaline)
A neurotransmitter produced primarily in the locus coeruleus, a small nucleus in the pons. Also the signalling molecule of the sympathetic nervous system.
Locus coeruleus
A small brainstem nucleus in the pons containing nearly all the brain's norepinephrine-producing neurons.
Monoamine neurotransmitters
A class including dopamine, norepinephrine, and serotonin. Produced by small numbers of neurons that modulate activity across the entire brain. Synthesised from the essential amino acid phenylalanine. Involved in alertness, arousal, sleep, attention, memory, and behavioural initiation.
Peptide neurotransmitters (neuropeptides)
Neurotransmitters composed of polypeptide chains (5–31 amino acids). Include opioids (enkephalins, dynorphins, beta-endorphin), oxytocin, vasopressin, substance P, orexin, and others.
Seizure
An event caused by excessive excitation and insufficient inhibition in neural circuits, setting off an explosive chain reaction of excitation.
Idiopathic seizure
A seizure with no identified cause. Most seizures are idiopathic. Often first appear in childhood.
Epilepsy
A clinical condition of recurring seizures.
Excitotoxicity
Cell death caused by overexcitation of neurons, typically through excessive activation of ionotropic glutamate receptors that allow large amounts of Ca++ into the cell.
CNS = brain + spinal cord.
PNS = everything else, connected to the CNS via the spinal cord or 12 pairs of cranial nerves.
Olfactory: nose, smell
Optic: retina, vision
Oculomotor: eye muscles, pupil constriction
Trochlear: eye muscles, eye movement
Trigeminal: face, facial sensation and movement
Abducens: eye muscles, eye movement
Facial: face, facial sensation/movement, salivation, lacrimation
Auditory-vestibular: inner ear, hearing and balance
Glossopharyngeal: tongue and pharynx, taste and movement
Vagus: pharynx, larynx, chest and abdominal organs, taste, heart rate, respiration
Accessory: neck muscles, movement
Hypoglossal: tongue, movement, swallowing, speech
Sympathetic ("fight or flight"):
Neurotransmitter at target tissues: norepinephrine (acts via GPCRs)
Increases heart rate, dilates airways, dilates pupils, inhibits salivation, inhibits bladder voiding, decreases intestinal motility
Parasympathetic ("rest and digest"):
Neurotransmitter at target tissues: acetylcholine (acts via GPCRs)
Decreases heart rate, constricts airways, constricts pupils, stimulates salivation, stimulates bladder voiding, stimulates intestinal motility
An agonist binds and activates a receptor. Every neurotransmitter is an agonist at its own receptor.
An antagonist binds a receptor but blocks the neurotransmitter's action without activating the receptor.
Sympathomimetic/sympatholytic drugs mimic or block sympathetic effects.
Parasympathomimetic/parasympatholytic drugs mimic or block parasympathetic effects.
Acetylcholine: basal forebrain nuclei, midbrain pontine nuclei. Broken down by acetylcholinesterase; synthesised by choline acetyltransferase.
Serotonin (5-HT): raphe nuclei (brainstem midline). Made from tryptophan in two enzymatic steps. Axons from raphe nuclei reach the entire brain.
Dopamine: substantia nigra and ventral tegmentum (VTA). Small clusters, but axons innervate large brain regions. GABA-producing cells also found in VTA.
Norepinephrine: locus coeruleus (pons). Relatively few neurons, but widespread projections.
Includes dopamine, norepinephrine, and serotonin.
All synthesised from the essential amino acid phenylalanine.
Produced by small populations of brainstem neurons that influence billions of cells throughout the cortex, cerebellum, and entire brain.
Collectively involved in global modulation of alertness, arousal, wakefulness, sleep, attention, memory, and behavioural initiation.
Polypeptides of 5–31 amino acids.
Include opioid peptides (enkephalins, dynorphins, beta-endorphin) and others such as vasopressin, oxytocin, substance P, somatostatin, orexin, neurotensin, neuropeptide Y, galanin, cholecystokinin.
Seizures result from an imbalance: too much excitation, too little inhibition.
Known causes include tumours disrupting circuitry, brain infections, high fevers, head trauma, and abrupt withdrawal from drugs that suppress neural activity (e.g. alcohol, sedative-hypnotics).
Most seizures are idiopathic (no identified cause); often first appear in childhood. About 1% of the US population experiences chronic, recurrent seizures.
Epilepsy is the clinical label for recurring seizures.
Antiseizure medications work by reducing excitation or enhancing inhibition: interfering with voltage-gated Na+, K+, or Ca++ channels, facilitating GABA's inhibitory action, or reducing glutamate's excitatory action.
Excitotoxicity occurs when excessive glutamate activation of ionotropic receptors allows too much Ca++ into neurons, causing cell death.
⚠️ Sympathetic = norepinephrine; parasympathetic = acetylcholine. Know which neurotransmitter goes with which branch and be able to list opposing effects on the same organ.
⚠️ Agonist vs. antagonist is foundational pharmacology vocabulary. A neurotransmitter is always an agonist at its own receptor.
⚠️ Know the location of each major neurotransmitter system: serotonin → raphe nuclei; dopamine → substantia nigra and VTA; norepinephrine → locus coeruleus; acetylcholine → basal forebrain and midbrain pontine nuclei.
⚠️ The monoamines (dopamine, norepinephrine, serotonin) are produced by small populations of neurons but modulate the entire brain. This "few neurons, massive reach" principle is commonly tested.
⚠️ Excitotoxicity links glutamate, ionotropic receptors, and Ca++ overload to cell death. A frequent exam topic, especially in the context of stroke and neurodegeneration.
⚠️ Antiseizure drugs target the excitation/inhibition balance. Be able to name the general mechanisms (block Na+/K+/Ca++ channels, boost GABA, reduce glutamate).
Q: What neurotransmitter does the sympathetic nervous system use at target tissue connections, and what receptor type does it act through?
A: Norepinephrine, acting through GPCRs (metabotropic receptors).
Q: Name the brainstem nucleus where most serotonergic neurons are found.
A: The raphe nuclei, located along the midline of the brainstem.
Q: What is the difference between an agonist and an antagonist?
A: An agonist binds to a receptor and activates it (producing a biological response). An antagonist binds to a receptor but blocks the neurotransmitter's action without activating the receptor.
Q: What is excitotoxicity, and which neurotransmitter is primarily involved?
A: Excitotoxicity is neuronal cell death caused by overexcitation, primarily through excessive glutamate activation of ionotropic receptors that allow large amounts of Ca++ to enter the cell.
Q: Why can abrupt withdrawal from alcohol or sedative-hypnotics increase seizure risk?
A: These drugs suppress neural activity (enhance inhibition). With chronic use, the brain adapts. When the drug is suddenly removed, the compensatory excitability is unopposed, tipping the excitation/inhibition balance toward excessive excitation.
Q: Which two brainstem nuclei are the primary sources of dopaminergic neurons?
A: The substantia nigra and the ventral tegmentum (VTA).
neuroanatomy, central nervous system, CNS, peripheral nervous system, PNS, cranial nerves, autonomic nervous system, sympathetic, parasympathetic, fight or flight, rest and digest, norepinephrine, noradrenaline, acetylcholine, neuromuscular junction, agonist, antagonist, sympathomimetic, sympatholytic, parasympathomimetic, parasympatholytic, serotonin, 5-HT, raphe nuclei, tryptophan, dopamine, substantia nigra, ventral tegmentum, VTA, locus coeruleus, monoamine, phenylalanine, peptide neurotransmitters, neuropeptides, opioids, enkephalins, endorphin, oxytocin, vasopressin, seizure, epilepsy, idiopathic, excitotoxicity, glutamate toxicity, antiseizure medication, excitation-inhibition balance