NS03 - Synaptic Transmission and CNS Circuits

Biomedical Sciences III

What are the three ways synapses are categorized?

By direction (presynaptic/postsynaptic), location (axodendritic, axosomatic, axoaxonic), and type (chemical or electrical).

What is the difference between chemical and electrical synapses?

Chemical synapses use neurotransmitters, have synaptic delay, are unidirectional, and Ca2+ dependent. Electrical synapses connect cells via gap junctions, allow near-instantaneous communication, and are often bidirectional.

What was the Loewi Experiment and what did it discover?

Loewi stimulated the vagus nerve of a frog heart, slowing its rate. Fluid from that heart slowed a second heart, showing the vagus nerve releases an inhibitory chemical—"vagusstoff"—later identified as acetylcholine.

What are the steps of synaptic transmission?

1) Action potential reaches presynaptic terminal

2) Ca2+ channels open

3) Ca2+ binds synaptotagmin

4) SNARE complex facilitates vesicle fusion

5) Neurotransmitter released

6) NT binds postsynaptic receptors

7) Ion channels open/close

8) NT removed by degradation or reuptake.

What is the SNARE complex and its components?

A protein group that docks vesicles at the membrane: Synaptobrevin (v-SNARE; binds to vesicles), SNAP-25 and Syntaxin (t-SNAREs; bind to membrane).

What does synaptotagmin do?

It is the Ca2+ sensor on vesicles that triggers neurotransmitter release when intracellular Ca2+ increases.

Why do tetanus toxin and botulinum toxin have different effects?

Botulinum blocks ACh release, causing flaccid paralysis. Tetanus blocks inhibitory signals to motor neurons, causing spastic paralysis and muscle spasms.

Where and how can synaptic transmission be altered?

1) Inhibit SNARE complex, 2) Block voltage-gated Ca2+ channels, 3) Block receptors, 4) Block reuptake, 5) Block enzyme degradation.

What happens at the postsynaptic membrane during synaptic transmission?

Neurotransmitter binds receptors, ion channels open/close, membrane potential changes (depolarization or hyperpolarization), and neurotransmitter is removed.

What are EPSPs and IPSPs?

EPSPs (depolarization) occur via Na+/K+ or Ca2+ channels; IPSPs (hyperpolarization) occur via K+ or Cl- channels.

What is summation in synaptic transmission?

Temporal summation: repeated signals from one neuron at different times. Spatial summation: signals from multiple neurons add together. If total EPSP – IPSP exceeds threshold, an action potential fires.

What are the two types of neurotransmitter receptors?

Ionotropic (direct ion channel opening) and metabotropic (G-protein coupled, indirect effects).

What are the main excitatory neurotransmitters in the CNS?

Glutamate and aspartate. Excess glutamate can cause excitotoxicity via increased intracellular Ca2+.

How do AMPA and NMDA receptors work together?

AMPA opens quickly (Na+/K+)

NMDA opens slowly (Na+, K+, Ca2+) and is blocked by Mg2+ at low Vm. (NMDA causes long term potentiation)

At –70 mV only AMPA opens; at –40 mV both open.

What is GABA and how is it synthesized?

GABA is the main inhibitory neurotransmitter in the brain, synthesized from glutamate via glutamate decarboxylase.

• Mainly only in the CNS

What is the GABA A receptor and what enhances it?

An ionotropic Cl- channel enhanced by benzodiazepines, barbiturates, neurosteroids, and ethanol.

• These depress the NS by activating GABA A receptors

What is glycine’s role in the CNS?

Glycine is an inhibitory neurotransmitter found mainly in spinal cord interneurons and circuits that relax antagonist muscles.

How are different types of neurotransmitters synthesized and released?

Neuropeptides and protein neurotransmitters are made in the cell body and prepackaged into vesicles. Small gaseous and lipophilic neurotransmitters are synthesized in the terminal and released directly without packaging.

What is neuromodulation and how does it differ from synaptic transmission?

Neuromodulators act via metabotropic receptors over diffuse areas, modulating neuron groups or brain regions with long-lasting, widespread effects on all neurons in the area.

What effects can metabotropic receptors have in the postsynaptic cell?

They can activate gene transcription, open ion channels indirectly, activate enzymes, and trigger intracellular chemical activators.

What is adrenergic neuromodulation?

Adrenergic neuromodulation increases spiking activity in response to a stimulus, causing heightened responsiveness and arousal.

What is the Reticular Activating System (RAS)?

Originates in the brainstem, activates the cortex, controls arousal and consciousness. Activity levels range from alertness to coma. Modulated by cholinergic and adrenergic systems.

What stimulates and inhibits the RAS?

Stimulated by: sensory signals (especially pain/proprioception), motor cortex, limbic system, sympathomimetics, and histamine. Inhibited by: sensory withdrawal, reticular formation damage, sleep centers, and anesthetics.

What are the major neuromodulatory systems and their functions?

Cholinergic (motor, memory, arousal), adrenergic (arousal, reward), dopamine (reward, motor, cognition), serotonin (mood, satiety, temperature), adenosine (inhibits cortical function, promotes sleepiness).

How is brain activity measured?

EPSPs cause net (+) influx and ECF negativity; IPSPs cause net (–) influx and ECF positivity. EEG diagnoses seizures, stroke, coma, etc.

What neurotransmitter imbalance is associated with Alzheimer’s disease?

Plaques in acetylcholine-producing neurons, leading to reduced ACh activity.

What neurotransmitter imbalance is associated with anxiety?

Reduced GABA activity, leading to decreased inhibition in the brain.

What neurotransmitter imbalance is associated with depression?

Complex abnormalities in cholinergic, catecholaminergic, and serotonergic transmission.

What neurotransmitter imbalance is associated with seizure disorders?

Increased glutamate and decreased GABA, leading to excessive excitation.

What neurotransmitter imbalance is associated with mania?

Increased norepinephrine and dopamine activity and reduced serotonin (5-HT) levels.

What neurotransmitter imbalance is associated with Parkinson’s disease?

Loss of dopaminergic neurons, leading to reduced dopamine levels.