Neurochemical Communication and Neurotransmitter Classes (class recording)

Diverse Forms of Synaptic Communication and Electrical Signals

• Beyond the Classic Axon-Dendritic Synapse: Neurochemical communication is highly diverse, extending beyond the typical axon-to-dendrite interaction.

  • Dendrite-to-Dendrite Communication: Synapses can form between dendrites.

  • Axon-Dendritic Communication: The most commonly discussed form, where the axon communicates with a dendrite.

  • Axon-Extracellular Communication: Neurotransmitters are released into the extracellular fluid and diffuse, potentially influencing distant receptor sites.

  • Axosomatic Communication: An axon binds directly to the neuron's cell body (soma).

  • Axosynaptic Communication: An axon sends information to an already formed synapse, modulating and influencing existing networks.

  • Axo-Axon Communication: One axon influences another axon.

  • Axosecretory Communication: Axons secrete neurotransmitters directly into the bloodstream, where they can act as hormones rather than neurotransmitters.

• Electrical Synapses (Gap Junctions):

  • Nature: These are fast, direct electrical connections between neurons, bypassing chemical communication when rapid communication is needed.

  • Mechanism: Electrical signals cross directly from one neuron to the next without neurotransmitter release.

  • Function: Allow for the exchange of function between glial cells and neurons, and selectively permit the passage of specific-sized molecules through larger channels, unlike the ion movement in chemical synapses.

Excitatory vs. Inhibitory Synapses: Structural and Functional Distinctions

• General Distinctions (Not Always Absolute): Excitation and inhibition can occur at the same synapse, but general structural differences are observed.

  • Excitatory Synapses (Excitatory Postsynaptic Potentials - EPSPs):

    • Location: Typically found on dendrites.

    • Vesicles: Neurotransmitters are packaged and released in round vesicles.

    • Membrane Material: Dense material on the membrane, indicating a high concentration of neurotransmitter release sites.

    • Cleft: Wide synaptic cleft.

    • Active Zone: Large active zone with many receptors to match the abundant neurotransmitter release, maximizing resource utility.

  • Inhibitory Synapses (Inhibitory Postsynaptic Potentials - IPSPs):

    • Location: Typically located on the cell body (soma).

    • Vesicles: Neurotransmitters are packaged in flat vesicles.

    • Membrane Material: Sparse material on the membrane, indicating less neurotransmitter release.

    • Cleft: Narrow synaptic cleft.

    • Active Zone: Small active zone with fewer receptors, matching the less abundant neurotransmitter release, optimizing resource use.

• Dendritic Spine Morphology and Synaptic Function:

  • Impact of Stress/Environment: The morphology of dendritic spines can change quickly due to factors like stress or environmental influences.

  • Healthy Spines: Healthy dendritic spines with wide clefts and numerous receptors are crucial for accommodating excitatory input and proper synaptic function.

  • Unhealthy Spines: Narrow, unhealthy dendritic spines have reduced receptor sites, impairing their ability to accommodate neurotransmitters and thus diminishing proper excitatory function.

  • Learning and Memory: Healthy, robust dendritic spines are essential for forming healthy synapses, facilitating learning, skill acquisition, and memory formation.

The Complex Nature of Neurotransmitters

• Beyond Simple Excitation/Inhibition: The human brain utilizes a vast array of neurotransmitters and receptors, making communication complex.

  • Modulatory Role: Many neurotransmitters are modulatory, meaning their effect (excitation or inhibition) depends on the specific system, network, and receptor they bind to.

  • Examples: While glutamate is generally excitatory and GABA inhibitory, many others operate context-dependently.

  • Co-transmission: Two or more neurotransmitters can operate at a single synapse, leading to additive or antagonistic effects, or enhanced potency.

  • Drug Influence: External substances like drugs can profoundly manipulate neurotransmitter systems.

    • Alcohol and Benzodiazepines: Both increase the inhibitory effects of GABA. Alcohol adds to GABA's influence, while benzodiazepines prolong the opening of GABA-gated chloride channels, leading to increased and longer-lasting inhibition.

• Multiple Receptor Varieties: A single neurotransmitter can interact with dozens to hundreds of different receptor types.

  • Example: Dopamine: Binds to various dopaminergic receptors (e.g., $D<em>1$, $D</em>2$, $D_3$).

  • Example: Glutamate: Binds to different receptor types, including AMPA receptors (e.g., glutamate types $1-5$) and NMDA receptors (e.g., glutamate types $1-3$), leading to massive scaling in their effects.

Criteria for a Neurotransmitter

• General Criteria (with expanding definitions):

  1. Presence/Synthesis: The transmitter must be synthesized in or otherwise present in the neuron.

     • Expansion: Not all are solely synthesized within the presynaptic neuron; some are synthesized in the cell body, axon terminal, or even with astrocytic help. Postsynaptic neurons can also synthesize neurotransmitters (e.g., gaseous neurotransmitters for retrograde communication).

  2. Release: The transmitter is released upon neuronal stimulation.

  3. Response: The released transmitter produces a response in the target neuron.

  4. Experimental Replication: The same action must be obtained when the transmitter is experimentally applied to the receptor.

  5. Removal Mechanism: There must be a specific mechanism for its removal from the synaptic cleft.

• Broadened Definition: Neurotransmitters can:

  • Carry messages from one neuron to another by influencing the voltage of the postsynaptic membrane (pre-to-post or post-to-pre).

  • Change the structure of a synapse, not just cause direct excitation/inhibition. For instance, excitation can lead to more receptors appearing on the surface, enhancing future activity.

  • Communicate in the opposite direction (retrograde communication) from postsynaptic to presynaptic neurons, influencing neurotransmitter release or reuptake (resource management).

Identifying Neurotransmitters

• Staining: Various techniques allow for the identification of specific chemicals within living cells. Often, receptors are stained rather than the neurotransmitter itself to observe activation.

• Stimulation: Neurons can be stimulated to observe subsequent neurochemical communication. For example, stimulating a frog heart releases acetylcholine, decreasing heart rate.

• Collection: Neurotransmitters can be collected from nervous system tissue (e.g., in cell cultures) to study their communication patterns.

Classes of Neurotransmitters

• Five General Classes:

  1. Small-molecule transmitters

  2. Peptide transmitters

  3. Lipid transmitters

  4. Gaseous transmitters

  5. Myelotransmitters

• Focus on Synthesis: Understanding synthesis provides perspective on general principles, influences, and activating systems.

Small-Molecule Transmitters

• General Characteristics: Typically quick-acting; often synthesized in the axon terminal; properties can be influenced by dietary nutrients.

• Contrast with Lipid Transmitters: Lipid transmitters are slower-acting, synthesized in the cell body.

1. Acetylcholine (ACh)

• Composition: Formed from acetate and choline.

• Synthesis and Breakdown: Synthesized in the intracellular fluid (neuron or with astrocytic help) from acetyl CoA and choline by choline acetyltransferase (CAT). Released $ACh$ binds to receptors and is then broken down by acetylcholinesterase (AChE) into choline and acetate, which can be reabsorbed for resynthesis.

• Pharmacological Influence: Medications that inhibit AChE prolong the action of acetylcholine in the synaptic cleft, offering a pathway for therapeutic intervention.

• Early Function Hint: Known to decrease heart rate and influence the peripheral