Study Guide: Lecture I

I. Overview (Slide 1)

Course Title: PSY-P457/PSY-657: Topics in Psychology - Neurophysiological basis of brain disorders

Lecture Title: Lecture 1: Introduction to Neurophysiology

Key Topics Covered:

Ionic basis of information transfer in the nervous system

The role of Glial cells in neuronal function

Passive properties of neurons

II. Ionic Composition of Nerve Cells (Slide 2)

"Seawater in Our Brain": This refers to the ionic composition of the extracellular and intracellular fluids in the brain which are similar to seawater.

Ionic Gradients: Crucial for electrical signaling in neurons. There is a difference in concentration of key ions between the extracellular and intracellular fluids.

Key Ions:

Sodium (Na+): Higher concentration outside the cell (150 mM), lower inside the cell (15 mM).

Potassium (K+): Higher concentration inside the cell (140 mM), lower outside the cell (5 mM).

Chloride (Cl-): Higher concentration outside the cell (120 mM), lower inside the cell (10 mM).

Anions (A-): Mostly large proteins; primarily concentrated inside the cell (100 mM).

Mechanisms of Ion Transport

A) Simple Diffusion: Solute moves directly across membrane from areas of higher concentration to lower concentration.

B) Channel-Mediated Diffusion: Facilitated diffusion of solute through channel protein.

C) Carrier-Mediated Diffusion: Facilitated diffusion of solute through carrier protein.

D) Active Transport: Solute moved against its concentration gradient with use of energy and an active protein.

E) Electrochemical Gradient: Diffusion of solute is determined by both the chemical gradient and electrical gradient.

Significance: This concentration difference forms the basis of the resting membrane potential and the ability to generate action potentials.

III. The Nernst Equation (Slide 3)

Purpose: Calculates the equilibrium potential (Eion) for a specific ion. This is the membrane potential at which there is no net movement of an ion across the membrane.

Equation:

Eion = (RT/zF) * 2.303 log ([ion]o / [ion]i)

Where:

Eion = equilibrium potential (in volts)

R = gas constant

T = absolute temperature

z = charge of the ion

F = Faraday's constant

[ion]o = ionic concentration outside the cell

[ion]i = ionic concentration inside the cell

Specific Examples:

Ek (Potassium): ~ -102 mV

ENa (Sodium): ~ +56 mV

ECl (Chloride): ~ -76 mV

Electrochemical Equilibrium: The movement of ions across a membrane is affected by both concentration gradients and electrical gradients.

Clinical Relevance: The slide mentions how the equilibrium potential of ions can be altered, for example, during epileptic seizures.

IV. Marked Changes in Extracellular Ion Concentration (Slide 4)

Concept: Extracellular ion concentrations change with different brain states (awake vs. sleep).

Key Ions and Changes:

Potassium (K+): Extracellular concentration is slightly higher during wakefulness than during sleep.

Calcium (Ca2+): Extracellular concentration is slightly higher during wakefulness than during sleep.

Magnesium (Mg2+): Extracellular concentration is slightly higher during wakefulness than during sleep.

Graphical Representation: Shows the fluctuations in ion concentration across the sleep-wake cycle.

Significance: These changes contribute to increased neuronal excitability during the awake state.

V. Maintaining Ion Concentrations: The Sodium-Potassium Pump (Slide 5)

Role of the Na+/K+ Pump: Uses active transport to maintain the ion gradients necessary for nerve function.

Mechanism:

Pumps 3 Na+ ions out of the cell.

Pumps 2 K+ ions into the cell.

Energy Consumption: Requires ATP (adenosine triphosphate) to function, making it an active transport process.

Result: Keeps the intracellular Na+ concentration low and the intracellular K+ concentration high, maintaining the necessary ion gradients.

VI. Resting Membrane Potential (Slide 6)

Concept: The voltage difference across the neuronal membrane when the neuron is at rest. It is not necessarily equivalent to the equilibrium potential for any specific ion.

Goldman-Hodgkin-Katz Equation: (Simplified on this slide):

Em = (PK+/Ptot) EK+ + (PNa+/Ptot) ENa+ + (PCl-/Ptot) * ECl-

Where:

Em = resting membrane potential

PK+, PNa+, PCl- = relative permeability of each ion

EK+, ENa+, ECl- = the Nernst potential for each ion

Ptot = the total permeability

Significance: The relative permeability of ions combined with their Nernst potentials, dictate the resting membrane potential of the cell.

Key Factors:

Membrane is more permeable to K+ at rest (due to leak channels) than Na+, resulting in a resting potential closer to the Ek.

VII. Key Points on Membrane Potential (Slide 7)

Summary of Concepts:

Differences in ion concentrations create electrical potential differences across the cell membrane.

This membrane potential is crucial for neurons to transmit electrical signals.

VIII. Types of Glia Cells in the CNS (Slide 8)

Main Types of Glial Cells

Astrocytes: Large cells with many processes that provide physical and metabolic support to neurons and regulate the extracellular environment. They originate from the ectoderm.

Oligodendrocytes: Cells that produce myelin in the central nervous system. They originate from the ectoderm.

Microglia: Immune cells of the CNS, involved in phagocytosis. They originate from the mesoderm.

Significance: Glial cells have a variety of important functions in brain health and function.

IX. Astrocytes Occupy Non-Overlapping Territories (Slide 9)

Concept: Astrocytes are not evenly distributed. They occupy specific territories and rarely overlap with other astrocytes.

Territorial Organization: Each astrocyte tends to have a distinct area that it monitors.

Significance: This organization suggests that each astrocyte can uniquely regulate a specific area of the nervous system.

X. Astrocytes Diversity in Primates and Humans (Slide 10)

Concept: In primates and humans, astrocytes have dramatically larger and more complex morphology than those in rodents.

Complexity: The figures highlight that human astrocytes have more processes and larger diameters.

XI. Functional Triad - Tripartite Synapse (Slide 11)

Concept: Astrocytes are active components of the synapse and act in conjunction with the pre and post synaptic neurons.

Key Components:

Astrocyte Process: Astrocytes are intimately associated with synapses.

Synaptic Bouton: Contains the presynaptic neuron, neurotransmitters and receptors.

Spine: Area of contact of the post-synaptic neuron.

Modulatory Role: Astrocytes have receptors for neurotransmitters and release "gliotransmitters" (e.g., glutamate, ATP, D-serine) to regulate synaptic transmission.

Clinical Relevance: Disruption in the tripartite synapse can result in neurological diseases.

XII. Potassium Syphoning by Astrocytes (Slide 12)

Concept: Astrocytes play a crucial role in regulating extracellular potassium (K+) concentrations.

Mechanisms:

Spatial Buffering: Astrocytes absorb excess K+ through channels and transporters (Kir4.1) when there is too much extracellular K+, and release K+ when there is too little extracellular K+ .

Gap Junctions: Astrocytes can form networks via gap junctions, allowing ions to move between cells to facilitate K+ syphoning.

Significance: By maintaining proper extracellular K+ levels, astrocytes help maintain neuronal excitability and prevent hyperexcitability or neuronal dysfunction.

Directionality: K+ uptake will occur when the extracellular K+ concentration is high, and K+ release will occur when the extracellular K+ concentration is low.

XIII. Key Points on Glia Cells (Slide 13)

Summary of Concepts:

Glia cells are active components of the nervous system, controlling synaptic transmission and extracellular K+ concentrations.

Astrocytes are highly complex and variable, especially in humans.

XIV. Passive Membrane Properties of Nerve Cells (Slide 14)

Concept: The passive electrical properties of neurons that affect how signals are propagated.

Spatial Decay: The graded potential dissipates exponentially with distance.

Length Constant (λ):

Defines how far a graded potential will travel passively along an axon.

λ = √ (rm / (r_i + r_o)), where

rm is the resistance of the membrane.

r_i is the resistance of the intracellular environment.

r_o is the resistance of the extracellular environment.

Relevance: A higher lambda means that a graded potential can travel further.

XV. Passive Properties - Ohm's Law (Slide 15)

Concept: The membrane can be represented by an RC circuit.

Ohm's Law: V=IR

Key Components:

R (Resistance): The measure of how much the membrane resists the flow of electrical current (e.g., ion flow)

I (Current): The flow of ions across the membrane

V (Voltage): The potential difference across the membrane

Significance: The membrane is an insulator of charge, but there are pathways for ions to pass through.

Graphical Representation: A cell can act as a resistor and capacitor and the voltage is directly proportional to the current input.

XVI. Passive Properties - Time Constant (Slide 16)

Concept: Describes how quickly the membrane potential changes in response to a current input.

Time Constant (τ): The time required for the membrane potential to reach 63% of its final value during a current injection.

τ = rm * cm, where:

* rm = membrane resistance

* cm = membrane capacitance

Relevance: A longer time constant means it takes longer for the membrane to change its potential.

Graphical Representation: Shows how the membrane potential increases when current is injected into the cell and then returns to resting potential when the current injection is stopped.

XVII. Passive Properties - Daily Oscillations (Slide 17)

Concept: Passive membrane properties of some nerve cells oscillate daily.

Examples: Membrane capacitance (Cm) and membrane time constant (τm) fluctuate in pyramidal cells, granule cells and PV+ cells across the day and night.

Graphical Representation: The figures show how these membrane properties vary over a 24-hour cycle.

Relevance: The passive membrane properties change over the day and this can impact synaptic integration.

XVIII. Passive Properties in Epilepsy (Slide 18)

Concept: Passive membrane properties are altered in disease states such as epilepsy.

Time Constant: The time constant of dentate granule cells is reduced in epileptic rats compared to controls.

Relevance: Changes in passive membrane properties can contribute to the excitability of neurons and increase susceptibility to seizures.

XIX. Key Points on Passive Membrane Properties (Slide 19)

Summary:

Both neurons and glia have passive membrane properties.

These properties can be approximated by an RC circuit.

Passive properties oscillate over a 24-hour day and can be altered in disease.

They play a crucial role in synaptic integration.

Study Questions:

WEquatigliotransmittersing the Nernst equation and understand its components.

Review Key Terms: Familiarize yourself with the vocabulary (e.g., Nernst potential, membrane potential, active transport, gliotransmittering membrane potential?

What are the different types of glial cells and their main functions?

What is meant by the concept of a tripartite synapse?

What is potassium syphoning and how do astrocytes contribute?

How do passive membrane properties affect signal propagation?

What is the length constant, and what factors influence it?

How can membrane capacitance and resistance be approximated in an RC circuit?

How do passive membrane properties change in pathological conditions like epilepsy?

Tips for Studying:

Focus on the Equatigliotransmittersing the Nernst equation and understand its components.

Visualize Processes: Use the diagrams and figures to understand ion movement, the Na+/K+ pump, and astrocyte function.

Relate Concepts: Connect the different topics (e.g., how ion gradients contribute to the membrane potential, how glia affects synaptic transmission).

Review Key Terms: Familiarize yourself with the vocabulary (e.g., Nernst potential, membrane potential, active transport, gliotransmitter, tripartite synapse, length constant, time constant)