3-4 quiz

Action Potentials and Toxins

• Blocking voltage-gated Na+ channels prevents action potentials from being generated, as seen with toxins like tetrodotoxin and saxitoxin.
• Batrachotoxin keeps sodium channels open, disrupting normal neural function.
• Agitoxin and beta-bungarotoxin inhibit voltage-gated K+ channels, impacting repolarization.

Neurotransmitter Release at Synapses

• Action potentials at the pre-synaptic terminal open voltage-gated Ca²⁺ channels.
• Ca²⁺ influx triggers synaptic vesicles to fuse with the membrane, leading to neurotransmitter release via exocytosis.
• SNARE proteins (v-SNARES and t-SNARES) facilitate vesicle docking and fusion at the presynaptic membrane.

Exocytosis Steps

• Ca²⁺ binds to synaptotagmin, a sensor that causes vesicles to move closer to the membrane, promoting fusion and neurotransmitter release.

Post-Synaptic Potentials (PSPs)

• The type of neurotransmitter released determines whether a PSP is excitatory or inhibitory.
• Excitatory PSPs (EPSPs) decrease membrane negativity, while inhibitory PSPs (IPSPs) increase negativity.

EPSP and IPSP Processing

• Cation influx results in depolarization (EPSP); anion influx or cation efflux leads to hyperpolarization (IPSP).
• Individual EPSPs and IPSPs are small; summation of these signals occurs in the dendrites.

Summation Types

• Spatial summation combines signals from multiple neurons at various cell parts.
• Temporal summation aggregates signals arriving at the axon hillock in quick succession.
• Successful integration of both types can trigger an action potential if the threshold is met.

Integrative Action Potential Generation

• Action potentials arise from the summation of excitatory and inhibitory inputs, with a threshold of -55 mV to -40 mV being critical.
• Excessive IPSPs can suppress excitability, preventing unregulated firing, as seen in seizure conditions.

Receptors and Neurotransmitter Action

• Ionotropic receptors allow ions to flow through when bound by neurotransmitters; NMDA receptors require both ligand binding and depolarization for activation.
• AMPA receptors' activation can lead to NMDA receptor opening, enhancing EPSP generation, crucial for cognitive functions like learning.

GABA and Glycine

• GABA serves as the main inhibitory neurotransmitter, acting on GABA receptors (GABAA, GABAC, and GABAB).
• GABAA receptors allow Cl⁻ influx, leading to IPSPs and have binding sites for sedatives and anesthetics that can prolong their effect.
• Glycine receptors are ionotropic and also mediate inhibitory signals primarily in the spinal cord and brainstem.

Seizures and Comas

• Excessive glutamate can trigger seizures, while excessive GABA can lead to coma.### Neuromodulatory Transmitters
• Neuromodulatory transmitters alter information processing in the CNS primarily through metabotropic actions.
• They can amplify or dampen signals without directly transferring information quickly.

Norepinephrine/Noradrenaline (NE)

• Originates in the locus coeruleus, projecting throughout the brain and body.
• Crucial for arousal, sleep/wake regulation, and mood, influencing stress and anxiety.
• Enhances cognitive function, particularly decision-making during stress responses.
• Acts through sympathetic nervous system; central to fight/flight responses.
• Metabotropic receptors include α1, α2, β1, and β2.
• Associated with anxiety, stress, hyperarousal; PTSD treatment can involve NE inhibitors.

Serotonin (5-HT)

• Produced in the dorsal raphe, with projections across various brain regions.
• Regulates sleep/wake cycles, feeding behavior, and mood, primarily through metabotropic receptors (15 types).
• Links to anxiety and depression; SSRIs (like Prozac) are common treatments.
• An imbalance of NE and 5-HT is noted in anxiety disorders, with excessive NE impacting serotonin levels.

Dopamine (DA)

• Different effects based on release locations within the brain.
• Originates in the ventral tegmental area, affecting limbic and cortical areas; key in reward and reinforcement.
• Involved in addiction pathways throughout the cortex.
• Another origin in the substantia nigra, projecting to the striatum, aids in motor control; depletion linked to Parkinson's disease.
• Metabotropic receptors range from D1 to D5.
• Disorders linked to dopamine include schizophrenia, drug addiction, and Parkinson's disease.

Acetylcholine (ACh)

• In the CNS, arises from the basal forebrain; released widely and linked to various projections.
• Involved in learning, memory, and attention; affected in Alzheimer’s disease.
• Utilizes ionotropic nicotinic receptors (also impacted by nicotine) and metabotropic muscarinic receptors.
• In the PNS, plays a role at the neuromuscular junction with ionotropic nicotinic ACh receptors crucial for muscle function.
• Lost cholinergic function is a critical feature in neurodegenerative diseases.