Synapse

Synapse: The junction between two neurons, consisting of a pre-synaptic axon terminal, a synaptic cleft, and a post-synaptic neuron/cell.
Neurotransmitters: Chemical messengers that facilitate communication between neurons.
Sources of Neurotransmitters: Originates at the cell body and are transported to the axon terminals for release.

Synaptic Transmission: The process through which neurotransmitters are released from a neuron and bind to receptors on a post-synaptic cell, leading to an excitatory or inhibitory response.
Action Potential: An electrical impulse that travels along the axon and triggers the release of neurotransmitters.
Graded Potentials: Changes in membrane potential induced by neurotransmitter binding at the synapse, which can lead to an action potential if the threshold is met.

Action Potentials: Trigger the opening of voltage-gated calcium (Ca²⁺) channels in the pre-synaptic axon terminal.
Calcium Petential: There is a higher concentration of Ca²⁺ outside the axon terminal; influx through facilitated diffusion occurs when voltage-gated channels open.

Process: Calcium influx triggers synaptic vesicles containing neurotransmitters to fuse with the membrane, releasing their contents into the synaptic cleft via exocytosis. This process requires ATP.
Recycle Process: Neurotransmitters are recycled through reuptake mechanisms or broken down by enzymes (e.g., acetylcholinesterase).

Neurotoxins: Substances that disrupt synaptic transmission or action potentials affecting neuronal communication. Their effects may lead to pain or numbness, flaccid paralysis, or seizures.

Target: Determine whether the neurotoxin affects the axon (action potentials) or synapse (synaptic transmission).
Action: Learn whether it causes more or fewer action potentials/synaptic transmissions.

Botulinum toxin: Prevents exocytosis of neurotransmitters, resulting in fewer synaptic transmissions.
Tetrodotoxin (TTX): Prevents opening of voltage-gated Na⁺ channels, leading to fewer action potentials.
Scorpion venom: Prevents closing of voltage-gated Na⁺ channels, causing more action potentials.
Cone snail venom & Spider venom (PhTx3): Prevents opening of voltage-gated Ca²⁺ channels, resulting in fewer synaptic transmissions.
Black Mamba venom (dendrotoxin): Prevents opening of voltage-gated K⁺ channels, leading to more action potentials.
Fasciculin (Green Mamba venom): Inhibits acetylcholinesterases at the synapse, resulting in more neurotransmitter activity.
Unidentified plant toxin: Inhibits neurotransmitter reuptake proteins, leading to more neurotransmitter in the synaptic cleft.

Reuptake Mechanism: Neurotransmitter recycling through serotonin reuptake proteins; blocking these can result in abundant neurotransmitter levels in the synaptic cleft (as seen with SSRIs in treated depressed individuals).
- Untreated Depression: Leads to excessive reuptake and insufficient neurotransmitter.
- Effect of SSRIs: Inhibits reuptake, increasing serotonin levels in the synapse, contributing to mood elevation.

Excitatory Post-Synaptic Potential (EPSP): Increases the likelihood of reaching threshold at the axon hillock (e.g., acetylcholine, serotonin).
- Threshold: Typically around -50 mV at the axon hillock.
Inhibitory Post-Synaptic Potential (IPSP): Decreases the likelihood of action potential (e.g., GABA, which opens Cl^- channels leading to hyperpolarization).
- Chloride Channels: Xanax causes ligand-gated Cl^- channels to remain open, affecting brain excitability.

Always refer to whether a neurotoxin causes increased or decreased activity: This approach helps in understanding the physiological implications without memorization of each toxin's effects specifically.

Figures and Illustrations: Refer to visual aids (like Figure 26.9) for clear understanding of synaptic mechanisms, neurotransmitter pathways, receptor interactions, and effects of specific neurotoxins.
ATP Cost: Emphasize that synthesis, transportation, exocytosis, and recycling of neurotransmitters require energy expenditure measured in ATP.

Understanding synaptic mechanisms and the role of neurotransmitters can help in developing drugs for various neurological conditions. The role of neurotoxins can also provide insights into pathophysiological processes related to neuronal damage and diseases.