Clase 11 Fisiología - Neurofisiología Sensitivo 2 (IG:@doctor.paiva)

Introduction to Neurophysiology

Overview of the Class

• Eduardo Pai introduces the first class on neurophysiology, focusing on synaptic transmission and neurotransmitters.

• The session will cover chemical substances acting as synaptic transmitters, types of action potentials in neurons, and neuronal summation (spatial and temporal).

• Special characteristics of synaptic transmission will be discussed, including effects of hypoxia and acid-base imbalance.

Types of Synaptic Transmitters

Classification of Neurotransmitters

• There are over 50 chemicals involved in synaptic transmission, categorized into fast-acting small molecules and slow-acting large neuropeptides.

Fast-Acting Small Molecules

• Fast-action neurotransmitters are synthesized in the presynaptic neuron's cytoplasm (except nitric oxide), stored in secretory vesicles, and released via exocytosis into the synaptic cleft.

Key Neurotransmitters

Acetylcholine

• Acetylcholine is released in the motor cortex and basal ganglia; it plays a crucial role in muscle stimulation.

• It has an excitatory effect generally but can be inhibitory in parasympathetic nervous system contexts (e.g., heart).

Norepinephrine

• Norepinephrine is produced in the locus coeruleus with mixed excitatory/inhibitory effects; it influences vasodilation.

Dopamine

• Dopamine originates from the substantia nigra; its deficiency leads to Parkinson's disease due to increased excitatory activity from basal ganglia.

Inhibitory Neurotransmitters

Glycine

• Glycine acts as an inhibitory neurotransmitter within the spinal cord, preventing movement during sleep to avoid conditions like sleepwalking.

GABA (Gamma-Aminobutyric Acid)

• GABA is primarily inhibitory, found in various brain regions. It interacts with receptors that also respond to substances like alcohol.

Excitatory Neurotransmitter: Glutamate

Role of Glutamate

Neurotransmitters and Pain Pathways

Role of Glutamate and Serotonin in Pain

• Glutamate is involved in pain pathways, while serotonin, secreted in the brainstem, has an inhibitory role in pain perception.

• Serotonin release occurs during positive experiences (e.g., eating chocolate with loved ones), enhancing mood and reducing pain sensitivity.

Nitric Oxide and Memory

• Nitric oxide is produced instantly in brain regions related to long-term behavior and memory; it differs from other neurotransmitters as it is not stored in vesicles.

Neuropeptides: Slow Acting Transmitters

• Neuropeptides are synthesized differently than traditional neurotransmitters; they are slow-acting and produced in ribosomes within the neural soma.

• Examples include growth hormone, substance P (linked to chronic pain), insulin, vasopressin, among others.

Action Potentials: Differences Across Neurons

• Rapid-action neurotransmitters like glutamate lead to acute pain responses, while neuropeptides like substance P contribute to chronic pain due to their slower action.

Synthesis of Neurotransmitters

• Fast-action neurotransmitter synthesis occurs at the presynaptic neuron level, whereas neuropeptide synthesis takes place at the soma.

Understanding Action Potentials

Resting States and Excitation Thresholds

• Large peripheral nerve fibers have a resting state of -90 mV with an excitation threshold of -65 mV; motoneuron somas have a resting state of -65 mV with a threshold of -45 mV.

Depolarization Process

• A stimulus must raise the membrane potential by 35 mV for depolarization to occur in large peripheral fibers. This triggers sodium influx followed by potassium efflux during repolarization.

Sensitivity Variations Among Neurons

• Motoneuron somas require only a 20 mV change for action potential initiation compared to larger fibers needing 35 mV, indicating higher sensitivity to ionic changes.

Mechanisms of Inhibition

Presynaptic Inhibition Mechanisms

• Presynaptic neurons can inhibit signals through GABA receptors or benzodiazepines that open chloride channels, leading to hyperpolarization by increasing negative charge inside the cell.

Potassium Ion Dynamics

• Increased potassium ion efflux also contributes to hyperpolarization; if more positive ions exit than enter, this results in a more negative internal environment for the neuron.

Understanding Synaptic Summation

Types of Synaptic Summation

• Each presynaptic terminal contributes an electrical stimulus of approximately 0.5 to 1 mV, which dissipates in about 15 milliseconds.

• There are two main types of summation: spatial and temporal summation.

Spatial Summation

• In spatial summation, multiple excitatory synapses activate simultaneously, each contributing to the overall potential.

• An example shows that four synapses firing do not reach the excitation threshold; however, with sixteen synapses firing, the threshold is reached leading to action potential.

Temporal Summation

• Temporal summation occurs when a single presynaptic terminal fires repeatedly before the previous stimulus dissipates (within 15 milliseconds).

• This repeated stimulation can accumulate enough voltage to reach the excitation threshold and trigger an action potential.

Characteristics of Synaptic Transmission

Neuronal Fatigue

• Neuronal fatigue occurs when repetitive stimuli lead to a decrease in firing frequency over time due to limited neurotransmitter availability.

• For instance, if a neuron has 10,000 vesicles of acetylcholine and receives rapid stimuli, it may deplete its supply quickly leading to fatigue.

Epileptic Seizures

• During epileptic seizures, neuronal fatigue acts as a defense mechanism; seizures typically last around 20 minutes to half an hour before subsiding due to this fatigue.

Mechanism of Fatigue

Physiological Changes in Neuronal Activity

Impact of Acidosis and Alkalosis on Neuronal Function

• Acidosis leads to a decrease in neuronal activity, potentially resulting in complete inhibition and coma. This condition does not return neurons to normal levels but attempts to balance them.

• In contrast, alkalosis increases neuronal excitability significantly, which can lead to seizures due to hyperexcitability. The resting membrane potential approaches the threshold for excitation.

Role of Oxygen and Pharmacological Agents

• Neuronal excitation is highly dependent on oxygen levels; even brief interruptions can cause a total loss of excitability in some neurons.

• Certain drugs like caffeine, theophylline, and theobromine (found in coffee, tea, and chocolate) enhance neuronal excitability. Conversely, analgesics raise the membrane threshold for excitation, thereby reducing synaptic transmission.

Reference Material