Source: Chapters 6–7, Lecture slides
Tags: chemical synapse, electrical synapse, neurotransmitter, glutamate, GABA, acetylcholine, serotonin, dopamine, norepinephrine, EPSP, IPSP, ionotropic receptor, metabotropic receptor, GPCR, summation, Otto Loewi, vagus nerve, CNS, PNS, autonomic nervous system, sympathetic, parasympathetic, enteric, seizure, epilepsy, EEG, excitotoxicity
These two lectures cover synaptic transmission (electrical and chemical synapses), the major neurotransmitters and their receptors, how excitatory and inhibitory signals are integrated by neurons, and the organisation of the nervous system into central, peripheral, and autonomic divisions. They also cover neural excitability, seizures, and epilepsy.
Electrical synapse (gap junction)
Uses connexon proteins (assemblies of six connexin subunits) to form direct channels between two cells. Allows bidirectional ion flow. Fast, but cannot support highly compartmentalised signalling.
Chemical synapse
Contains presynaptic and postsynaptic terminals separated by a synaptic cleft. The presynaptic terminal releases neurotransmitters from synaptic vesicles into the cleft. Neurotransmitters bind receptors on the postsynaptic terminal to pass the signal.
Neurotransmitter
A signalling molecule, commonly an amino acid or other small molecule, released at synapses to transmit signals between neurons.
Synaptic vesicle
A membrane-enclosed structure in the presynaptic terminal that stores neurotransmitter molecules for release.
Synaptic cleft
The space between the presynaptic and postsynaptic terminals across which neurotransmitters are released.
Neurotransmitter receptor
A membrane-bound protein on the postsynaptic terminal that binds neurotransmitters to propagate the signal.
Reuptake transporter
A channel protein on the presynaptic terminal that reabsorbs neurotransmitter (or its breakdown products) from the synaptic cleft. Allows recycling and regulates how long the signal lasts.
Dendritic spine
The part of a neuron that receives signals from other neurons and processes them before sending them along the axon.
Ionotropic receptor
A receptor protein that is itself part of a ligand-gated ion channel. When a neurotransmitter binds, the channel changes shape and opens, allowing ions (Na⁺, K⁺, Ca²⁺, or Cl⁻) to flow through. Fast-acting.
EPSP (excitatory postsynaptic potential)
A change in membrane potential that makes the postsynaptic neuron more likely to fire an action potential (depolarisation). Many summed EPSPs are needed to reach threshold. Main neurotransmitter: glutamate.
IPSP (inhibitory postsynaptic potential)
A change in membrane potential that makes the postsynaptic neuron less likely to fire (hyperpolarisation, moving further from threshold). Main neurotransmitter: GABA.
Spatial and temporal summation
EPSPs and IPSPs arriving at different dendrites (spatial) or at different times (temporal) are summed at the axon hillock. Whether the net sum reaches threshold determines whether an action potential fires.
Metabotropic receptor (GPCR)
A receptor linked to a G-protein rather than directly to an ion channel. Neurotransmitter binding activates the G-protein, which triggers a secondary messenger cascade. Slower but more varied effects than ionotropic receptors.
GPCR signalling cascade
Neurotransmitter binds receptor, G-protein changes conformation, GDP is replaced by GTP, the activated G-protein subunit interacts with an effector enzyme (e.g. adenylate cyclase), which converts ATP to cAMP. cAMP activates protein kinases that phosphorylate substrate proteins, leading to amplified cellular effects.
Transcription factor
A protein that regulates gene transcription (DNA to RNA). Can be activated via GPCR signalling cascades: for example, cAMP can phosphorylate a transcription factor, which then enters the nucleus to activate or repress gene expression.
Glutamate
The most common neurotransmitter in vertebrates. Excitatory. An amino acid. Its receptors in the brain are ionotropic Na⁺ or Ca²⁺ channels. When glutamate binds, Na⁺ or Ca²⁺ flows in, causing depolarisation (EPSP).
GABA (gamma-aminobutyric acid)
The second most common neurotransmitter in vertebrates and the primary inhibitory neurotransmitter in the human brain. Synthesised from glutamate by the enzyme glutamic acid decarboxylase. Receptors are ionotropic Cl⁻ channels; when open, Cl⁻ flows in, causing hyperpolarisation (IPSP).
Glutamic acid decarboxylase
The enzyme that converts glutamate to GABA.
Acetylcholine (ACh)
The first neurotransmitter to be discovered. Released by the vagus nerve (PNS), at the neuromuscular junction, and produced in basal forebrain nuclei and midbrain pontine nuclei. Not made of amino acids. Broken down by acetylcholinesterase; breakdown products are recycled via reuptake transporters.
Serotonin (5-hydroxytryptamine)
Produced in the raphe nuclei, circulates throughout the brain. Also found in the GI tract and blood platelets. Synthesised from the amino acid tryptophan. Involved in constriction and dilation of blood vessels.
Dopamine
Plays a major role in reward-motivated behaviour. Most rewards increase dopamine levels; many addictive drugs increase dopamine activity. Also involved in motor control and hormone release. Produced in the ventral tegmentum and substantia nigra. Synthesised from the amino acid phenylalanine.
Norepinephrine
Mobilises the brain and body for action. Lowest during sleep, rises with wakefulness, peaks during stress (fight-or-flight). In the brain: increases arousal, alertness, memory formation and retrieval, attention, anxiety. In the body: increases heart rate and blood pressure. Produced in the locus coeruleus. Excitatory neurotransmitter in the sympathetic nervous system. Made from amino acids.
Otto Loewi
Demonstrated chemical neurotransmission in 1920 using frog heart experiments. Stimulated the vagus nerve of one heart, then transferred the surrounding fluid to a second heart, which also slowed its beating. This showed that a chemical substance (later identified as acetylcholine) was released into the solution.
Vagus nerve
A cranial nerve in the PNS that signals to the heart using acetylcholine, decreasing heart rate.
Vagusstoff
The name Otto Loewi gave to the substance released by the vagus nerve, later identified as acetylcholine.
Electrical synapses use gap junctions (connexons made of connexin subunits) for direct, bidirectional ion flow
Chemical synapses use neurotransmitter release across a synaptic cleft for more complex, modulable signalling
Chemical synapses allow for excitation or inhibition, transient or sustained effects, and signal amplification
Ionotropic: the receptor is the channel. Neurotransmitter binding opens the pore directly. Fast.
Metabotropic (GPCR): neurotransmitter binding activates a G-protein, which triggers a secondary messenger cascade. Slower, but can produce diverse, amplified, and long-lasting effects.
GPCR cascade: neurotransmitter binds, G-protein activated (GDP swapped for GTP), activated subunit reaches effector enzyme (e.g. adenylate cyclase), ATP converted to cAMP, cAMP activates protein kinases, which phosphorylate downstream targets
Individual EPSPs and IPSPs are usually too small on their own to trigger an action potential
Spatial summation: inputs from multiple synapses at different locations on the neuron
Temporal summation: rapid, repeated inputs from the same synapse
The net sum at the axon hillock determines whether threshold is reached
Glutamate: most common excitatory NT, ionotropic Na⁺/Ca²⁺ channels, produces EPSPs
GABA: primary inhibitory NT, synthesised from glutamate, ionotropic Cl⁻ channels, produces IPSPs
Acetylcholine: first NT discovered, used at neuromuscular junction and by the vagus nerve, produced in basal forebrain and midbrain pontine nuclei
Serotonin: produced in raphe nuclei, from tryptophan, found in brain, GI tract, and blood
Dopamine: reward, motor control, hormone release, produced in ventral tegmentum and substantia nigra, from phenylalanine
Norepinephrine: arousal, fight-or-flight, produced in locus coeruleus, from amino acids
Monoamine neurotransmitters (serotonin, dopamine, norepinephrine) are derived from essential amino acids in the diet
They regulate cognitive processes including emotion, arousal, and certain types of memory
CNS: brain and spinal cord
PNS: everything else, connected to CNS by cranial nerves (directly to brainstem) and spinal nerves
Sensory division: eyes, ears, nose, skin
Motor division: muscles
Autonomic division: respiration, blood pressure, heart rate
Sympathetic: fight or flight, uses norepinephrine as excitatory NT
Parasympathetic: rest and digest, uses acetylcholine as NT
Enteric system: an independent nervous system in the gut, largely responsible for regulating digestion
Olfactory: smell
Optic: sight
Auditory-vestibular: sound
Vagus: heart rate (parasympathetic)
Where the nervous system signals to muscles
The synaptic terminal signals directly to receptor proteins on the muscle fibre (rather than to another neuron)
Agonist: a molecule that binds to and activates a receptor
Antagonist: a molecule that binds to a receptor and blocks the action of the neurotransmitter
Sympathomimetic: stimulates the sympathetic nervous system
Sympatholytic: decreases sympathetic nervous system effects
Parasympathomimetic: increases parasympathetic nervous system activity
Parasympatholytic: decreases parasympathetic nervous system effects
EEG (electroencephalography): records electrical impulses of the brain from the scalp
Cortical neuropil: closely packed structure of glial and neural cells in the vertebrate brain
Seizure: runaway neural activity in the brain, can cause auras, muscle convulsions, amnesia, loss of consciousness
Causes: tumours disrupting neural circuitry, infection, high fever
Unknown cause = idiopathic seizure
Triggers: sleep deprivation, stress, head trauma, stimulant drug use
Treatment: anti-seizure medications that interfere with voltage-gated Na⁺ channels
Epilepsy: chronic or recurrent seizures
Electrocorticography (ECoG): electrodes placed directly on the brain surface (under the skull), invasive, used before surgery to remove epileptogenic tissue
Treatments for epilepsy: medications to decrease excitability, surgical severing of the corpus callosum, excision of epileptogenic brain tissue
Excitotoxicity: over-excitation of neurons during seizures causes cell death
⚠️ Know the difference between ionotropic (fast, direct channel) and metabotropic (GPCR, slower cascade) receptors.
⚠️ Glutamate = excitatory (EPSP), GABA = inhibitory (IPSP). Know the enzyme that converts glutamate to GABA (glutamic acid decarboxylase).
⚠️ Spatial and temporal summation at the axon hillock determines whether an action potential fires.
⚠️ Loewi's frog heart experiment proved chemical neurotransmission. Know the substance released was later identified as acetylcholine.
⚠️ Know sympathetic (norepinephrine, fight-or-flight) vs. parasympathetic (acetylcholine, rest-and-digest).
⚠️ The enteric nervous system is independent, located in the gut, and not part of the CNS or PNS proper.
⚠️ Agonist activates a receptor; antagonist blocks it.
⚠️ Know where each major neurotransmitter is produced (raphe nuclei for serotonin, locus coeruleus for norepinephrine, ventral tegmentum/substantia nigra for dopamine, basal forebrain for ACh).
Q: What is the difference between an ionotropic and a metabotropic receptor?
A: An ionotropic receptor is a ligand-gated ion channel that opens directly when a neurotransmitter binds. A metabotropic receptor (GPCR) activates a G-protein, which triggers a secondary messenger cascade, producing slower but more varied effects.
Q: What neurotransmitter did Otto Loewi's frog heart experiment identify?
A: Acetylcholine (initially called Vagusstoff).
Q: What enzyme converts glutamate to GABA?
A: Glutamic acid decarboxylase.
Q: What is the difference between spatial and temporal summation?
A: Spatial summation combines inputs arriving at different synapses (different locations) on the neuron simultaneously. Temporal summation combines inputs arriving rapidly in succession at the same synapse.
Q: What neurotransmitter is used by the sympathetic nervous system, and what is its general effect?
A: Norepinephrine. It mobilises the body for action (fight-or-flight): increasing heart rate, blood pressure, arousal, and alertness.
Q: What is excitotoxicity?
A: Cell death caused by excessive excitation of neurons, as occurs during seizures.
Q: What is the role of the enteric nervous system?
A: It is an independent nervous system in the gut that primarily regulates digestion. It operates largely independently of the CNS and PNS.
Chemical synapse, electrical synapse, gap junction, connexin, connexon, neurotransmitter, synaptic vesicle, synaptic cleft, reuptake, dendritic spine, ionotropic receptor, metabotropic receptor, GPCR, G-protein, secondary messenger, cAMP, protein kinase, transcription factor, EPSP, IPSP, summation, spatial summation, temporal summation, glutamate, GABA, glutamic acid decarboxylase, acetylcholine, serotonin, dopamine, norepinephrine, monoamine, Otto Loewi, vagus nerve, Vagusstoff, CNS, PNS, autonomic, sympathetic, parasympathetic, enteric, neuromuscular junction, agonist, antagonist, sympathomimetic, sympatholytic, parasympathomimetic, parasympatholytic, EEG, seizure, epilepsy, excitotoxicity, ECoG, idiopathic, MCB C61, UC Berkeley