Neuroscience and Neuronal Communication Flashcards

Cellular Architecture and Glial Support in the Nervous System

• Peripheral Nervous System Glial Cells (Schwann Cells):

  • Definition and Location: Schwann cells are a primary type of neuroglial cell found exclusively within the Peripheral Nervous System (PNS).
  • Myelination Function: Schwann cells wrap around the axons of peripheral neurons to form the myelin sheath. This lipid-rich insulating layer increases the rate at which an action potential travels down the axon via saltatory conduction.
  • Axonal Regeneration: Schwann cells actively assist in the regrowth and regeneration of damaged or severed peripheral axons by phagocytosing cellular debris and forming a continuous structural pathway known as a regeneration tube (Büngner bands).

• Structural Support in the Nervous System:

  • Structural Matrix: The structural scaffolding and physical matrix for neurons throughout the nervous system is primarily provided by neuroglial cells (such as astrocytes in the Central Nervous System). These cells physically anchor neurons, support extracellular homeostatic balance, and maintain structural integrity.

• Intracellular Material Transport:

  • Cytoskeletal Transport Mechanics: The internal movement and transport of materials, vesicles, organelles, and proteins inside a neuron are driven by microtubules working in tandem with specialized molecular motor proteins (kinesin and dynein).
  • Directional Pathways:
  • Anterograde Transport: Transports materials from the soma (cell body) down the axon toward the axon terminal, powered primarily by kinesin motor proteins.
  • Retrograde Transport: Transports materials and signaling molecules from the axon terminal back toward the soma, powered primarily by dynein motor proteins.

Neuronal Populations and Functional Anatomy

• Predominant Cortical Neurons:

  • Pyramidal Neurons: Pyramidal cells constitute the vast majority (approximately $70\%$ to $80\%$) of the total neuronal population within the cerebral cortex.
  • Structural Features and Role: Characterized by a pyramid-shaped cell body, a long apical dendrite extending toward the cortical surface, multiple basal dendrites, and a single axon, these cells serve as the principal excitatory projection neurons of the cortex using glutamate as their primary neurotransmitter.

• Neuronal Signal Reception:

  • Dendrites and Dendritic Spines: Dendrites are the specialized, branching structures of a neuron that typically receive incoming electrical and chemical signals from the presynaptic axon terminals of other neurons. Specialized dynamic microstructures called dendritic spines further expand the receptive surface area for synaptic inputs.

• Inter-regional Communication in the Central Nervous System:

  • Central Nervous System Neurons: Neurons (including interneurons and projection neurons) located within the Central Nervous System (CNS) are primarily responsible for integrating processing and driving communication both within specific brain regions and across pathways connecting different brain regions.

Electrochemical Dynamics of Neuronal Communication

• Resting Membrane Potential ($-70\,\text{mV}$):

  • Physical Interpretation: Saying that a neuron has a resting potential of $-70\,\text{mV}$ means that the interior (intracellular fluid) of the cell membrane is electrically negative relative to the exterior (extracellular fluid) by a potential difference of $70\,\text{mV}$.
  • Ionic Foundations: This electrical baseline is created and maintained by unequal ionic distribution across the plasma membrane:
  • High concentration of potassium ions ($\text{K}^+$) and fixed organic anions ($\text{A}^-$) inside the cell.
  • High concentration of sodium ions ($\text{Na}^+$) and chloride ions ($\text{Cl}^-$) outside the cell.
  • Continuous operation of the sodium-potassium pump ($\text{Na}^+/\text{K}^+$ ATPase), which actively transports $3\,\text{Na}^+$ out of the cell for every $2\,\text{K}^+$ brought inside.

• Action Potential Initiation Dynamics:

  • Sodium Influx: At the beginning of an action potential (the rapid depolarization phase), voltage-gated $\text{Na}^+$ channels open rapidly upon reaching threshold potential (typically around $-55\,\text{mV}$).
  • Direction of Movement: Driven down both its chemical concentration gradient and electrical gradient, $\text{Na}^+$ moves inward (influx) into the intracellular compartment.

• Refractory Periods and Hyperpolarization:

  • Relative Refractory Period: The period immediately following an action potential during which a standard depolarizing input is insufficient to trigger a subsequent action potential, requiring a suprathreshold (stronger than normal) stimulus.
  • Underlying Cause: This period occurs because the membrane potential undergoes hyperpolarization, becoming more negative (e.g., $-80\,\text{mV}$ to $-90\,\text{mV}$) than the baseline resting potential of $-70\,\text{mV}$. This is caused by the delayed closure of voltage-gated $\text{K}^+$ channels leading to continued $\text{K}^+$ efflux.

• Excitatory vs. Inhibitory Postsynaptic Signalling:

  • Excitatory Postsynaptic Potential (EPSP): Occurs when neuron A transmits a signal to neuron B that depolarizes the postsynaptic membrane, bringing its potential closer to threshold and increasing the likelihood of an action potential occurring in neuron B.
  • Inhibitory Postsynaptic Potential (IPSP) and GABA Action:
  • GABA Function: Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the brain.
  • Hyperpolarization Mechanism: Binding of GABA to postsynaptic receptors causes an influx of negative chloride ions ($\text{Cl}^-$) or efflux of potassium ions ($\text{K}^+$), which hyperpolarizes the postsynaptic membrane.
  • Functional Consequence: Hyperpolarization makes the interior of the neuron more negative relative to the outside, driving the membrane potential further away from threshold and decreasing the likelihood of firing an action potential.

Receptor Subtypes and Signal Transduction Pathways

• Metabotropic vs. Ionotropic Receptor Action:
  • Pharmacological Scenario Analysis: Dr. Probst is observing the effects of a new drug that acts on postsynaptic receptors specifically linked to G-proteins (secondary messengers) to produce long-lasting physiological effects.
  • Receptor Target: The drug studied by Dr. Probst acts on metabotropic receptors (also called G-protein coupled receptors or GPCRs).
  • Comparative Distinctions:
  • Ionotropic Receptors: Ligand-gated ion channels that open directly upon neurotransmitter binding, yielding rapid, short-duration postsynaptic responses.
  • Metabotropic Receptors: Receptors that activate intracellular G-proteins upon ligand binding. This initiates intracellular secondary messenger cascades (such as cyclic AMP, $\text{IP}_3$, or $\text{DAG}$), resulting in slower-onset, long-lasting cellular modifications and potential modulation of gene expression.

Chronological Sequence of Synaptic Transmission and Action Potential Phases

• Chronological Order of Chemical Communication Between Neurons:

  1. Action Potential Arrival: An action potential travels down the axon of the presynaptic neuron and depolarizes the presynaptic axon terminal.
  2. Voltage-Gated Calcium Influx: Depolarization opens voltage-gated $\text{Ca}^{2+}$ channels in the presynaptic terminal, allowing $\text{Ca}^{2+}$ ions to flow inward.
  3. Vesicle Exocytosis: Influx of $\text{Ca}^{2+}$ causes synaptic vesicles loaded with neurotransmitters to fuse with the presynaptic membrane and release neurotransmitters into the synaptic cleft.
  4. Diffusion Across Synaptic Cleft: Neurotransmitter molecules diffuse across the narrow extracellular space separating the two neurons.
  5. Postsynaptic Receptor Binding: Neurotransmitters bind specifically to complementary postsynaptic receptors (ionotropic or metabotropic).
  6. Postsynaptic Potential Generation: Receptor binding opens or closes ion channels, inducing localized depolarization (EPSP) or hyperpolarization (IPSP) in the postsynaptic cell.
  7. Signal Termination: Neurotransmitter action is terminated by enzymatic degradation, reuptake back into the presynaptic terminal or surrounding glial cells, or passive diffusion away from the synaptic cleft.

• Action Potential Graph Phase Breakdown:

  • Resting State: Baseline membrane potential is maintained at $-70\,\text{mV}$ by passive leak channels and the $\text{Na}^+/\text{K}^+$ ATPase pump.
  • Threshold Potential: A depolarizing stimulus pushes the membrane potential to threshold (approx. $-55\,\text{mV}$).
  • Depolarization Phase: Opening of voltage-gated $\text{Na}^+$ channels leads to rapid $\text{Na}^+$ influx, driving membrane potential up to a positive peak of approx. $+30\,\text{mV}$ to $+40\,\text{mV}$.
  • Repolarization Phase: Voltage-gated $\text{Na}^+$ channels undergo inactivation while voltage-gated $\text{K}^+$ channels open fully, allowing rapid $\text{K}^+$ efflux that lowers membrane potential back toward negative values.
  • Hyperpolarization (Undershoot) Phase: Slow closure of $\text{K}^+$ channels results in excessive $\text{K}^+$ efflux, dropping potential lower than baseline (e.g., $-80\,\text{mV}$) and causing the relative refractory period.
  • Restoration: The cell returns to its baseline resting potential of $-70\,\text{mV}$ through standard ionic pump and leak channel activity.