15. Synaptic Integration Part 2 - The Role of Neurotransmitters

What happens at excitatory and inhibitory synapses during the patellar reflex?

• Patellar (knee-jerk) reflex involves both excitation and inhibition.

• Excitation: Ia sensory neuron activates α-motor neuron → quadriceps contract.

• Inhibition: same Ia sensory neuron activates inhibitory interneuron → inhibits α-motor neuron to hamstrings, preventing antagonist contraction.

• Ensures coordinated movement (one muscle contracts while the opposite relaxes).

Where do depolarization and hyperpolarization occur in the patellar reflex circuit?

• Depolarization:

  • Between Ia sensory neuron and α-motor neuron for quadriceps.

  • Between sensory neuron and inhibitory interneuron that affects hamstring motor neuron.

• Hyperpolarization:

  • Between inhibitory interneuron and α-motor neuron to hamstrings.

• Allows coordinated contraction and relaxation of opposing muscles.

Which neurotransmitters are involved in coordinating excitation and inhibition in the patellar reflex?

• Glutamate:

  • Released by Ia sensory neurons at excitatory synapses.

  • Activates α-motor neurons to quadriceps and interneurons.

• Glycine:

  • Released by inhibitory interneurons in the spinal cord.

  • Inhibits α-motor neurons to hamstrings (antagonist).

What are the key structural features of a synapse seen under electron microscopy?

• Presynaptic active zone: site of neurotransmitter release.

• Postsynaptic density: region containing receptors, directly across from active zone.

• Synaptic cleft: space between pre- and postsynaptic membranes.

• Synaptic vesicles: store high concentrations of neurotransmitters, released into cleft upon activation.

What are the four main criteria for classifying a neurotransmitter?

1. Synthesized in the presynaptic neuron.

2. Present in terminal and released in sufficient amounts to affect postsynaptic cell.

3. When applied externally, mimics the natural transmitter’s action (same receptors/pathways).

4. Has a specific removal mechanism from synaptic cleft (e.g., reuptake or degradation).

What are small-molecule neurotransmitters?

• Include acetylcholine, glutamate, GABA, glycine, dopamine, serotonin, norepinephrine.

• Typically rapid-acting.

• Synthesized locally in axon terminals.

• Mediate fast synaptic transmission.

What are peptide neurotransmitters and their general features?

• Short chains of amino acids (e.g., substance P, endorphins, oxytocin, vasopressin).

• Synthesized in cell body, packaged into vesicles, and transported to terminals.

• Usually modulate slower, longer-lasting synaptic effects.

Where are small-molecule and peptide neurotransmitters synthesized?

• Small-molecule neurotransmitters: synthesized at nerve terminals by local enzymes.

• Peptide neurotransmitters: synthesized in cell body along with modifying enzymes → transported down axon.

How is neurotransmitter release controlled at the presynaptic active zone?

• Release via exocytosis controlled by SNARE complex.

• Priming phase: SNAREs partially zippered; complexin clamps them.

• Action potential → Ca²⁺ influx → synaptotagmin binds Ca²⁺ + phospholipids + SNAREs → triggers vesicle fusion & pore opening → neurotransmitter released.

How do receptors mediate the effects of neurotransmitters in spinal circuits?

• Glutamate receptors: on α-motor neurons to quadriceps → excitatory depolarization.

• Glycine receptors: on α-motor neurons to hamstrings → inhibitory hyperpolarization.

• Together, they coordinate excitation and inhibition for proper reflex response.

How does glutamate produce excitatory synaptic transmission?

• Acts on ionotropic receptors: AMPA, kainate, NMDA (and some metabotropic).

• AMPA & kainate: allow Na⁺ in, K⁺ out → EPSP (Na⁺ dominates).

• NMDA: requires glutamate + glycine + depolarization to remove Mg²⁺ block → allows Na⁺ & Ca²⁺ influx.

• Ca²⁺ acts as an intracellular messenger, influencing plasticity and signaling.

How do glycine and GABA mediate inhibitory synaptic transmission?

• Glycine: major inhibitory transmitter in spinal cord; opens Cl⁻ channels via ionotropic receptors → hyperpolarization.

• GABA: major inhibitory transmitter in brain; acts on

  • GABAᴀ: ionotropic → opens Cl⁻ channels.

  • GABAʙ: metabotropic → activates K⁺ channels or inhibits Ca²⁺.

• Both decrease neuronal excitability.

How are neurotransmitters removed from the synaptic cleft?

• Reuptake: transporters move neurotransmitters back into presynaptic terminal.

• Glial uptake: glial cells absorb transmitter → convert to precursor form for reuse.

• Ensures signal termination and recycling of neurotransmitters.

How can drugs alter synaptic transmission?

1. Alter synthesis, storage, transport, or release of neurotransmitters.

2. Modify receptor interaction (agonist/antagonist effects).

3. Influence reuptake or degradation mechanisms.

4. Replace deficient neurotransmitters with substitutes.

How does botulinum toxin affect neurotransmission?

• Produced by Clostridium botulinum.

• Cleaves SNARE proteins → prevents acetylcholine release at neuromuscular junction.

• Causes flaccid paralysis (muscle cannot contract).

• Used therapeutically/cosmetically to relax muscles (e.g., Botox).