Neurons and Glial Cells

• Key topics covered in the lectures include neuron structure and function, glial cells, membrane potential, and electrical properties of neurons
• The notes also review relevant equations like the Nernst and Goldman equations

Neuron Doctrine

• Golgi's reticular theory posited that neurons are interconnected in a continuous network
• Cajal's neuron doctrine established that neurons are discrete cells communicating via synapses

Neuron Components

• Soma is the cell body and contains the nucleus
• Axons conduct electrical impulses
• Dendrites receive signals from other neurons

Neuronal Structure and Function

• Rough ER synthesizes proteins
• Mitochondria provides energy for the cell

Nissl vs Golgi Stains

• Golgi stains the entire neuron, but just a few cells
• Golgi uses silver nitrate and stains neurons black
• Nissl stains ribosomes and highlights the soma
• Nissl staining is useful for identifying neurons

Neuron and Glial Cell Types

• Neural cells are characterized by their ability to generate action potentials
• Glial cells support and regulate the central nervous system

Organelle Function

• Mitochondria generates ATP for energy
• Smooth ER synthesizes proteins, neurotransmitters, regulates calcium levels, and manages lipid synthesis
• Rough ER synthesizes proteins

Axoplasmic Transport

• Anterograde transport uses kinesin to move materials from the soma to the axon terminal
• Retrograde transport uses dynein to move materials back to the soma
• Both anterograde and retrograde transport require ATP

Neuron Classification

• Unipolar neurons have a single neurite that branches into a dendrite and an axon
• Bipolar neurons have one dendrite and one axon
• Multipolar neurons have many dendrites and one axon
• Anaxonic neurons have only dendrites, no axon
• Sensory (afferent) neurons carry signals to the CNS
• Motor (efferent) neurons carry signals away from the CNS
• Interneurons connect sensory and motor neurons

Glial Cells and Associated Disorders

• Astrocytes regulate the blood-brain barrier, and are implicated in Alzheimer’s disease
• Oligodendrocytes myelinate CNS axons, and are affected in multiple sclerosis
• Microglia are immune cells, and play a role in neurodegenerative diseases like ALS
• Schwann cells myelinate PNS axons, and are affected in MS and ALS
• Ependymal cells produce CSF
• Ependymoma and Alzheimer’s are associated with Ependymal cells

Cytoskeleton

• The cytoskeleton supports axonal transport and cell shape
• Disruptions in microtubules are implicated in Alzheimer’s and Parkinson’s diseases

Blood Brain Barrier (BBB)

• The BBB protects the brain
• Disruption of the BBB can result in neuroinflammation, meningitis, and stroke

Resting Membrane Potential (RMP)

• Ion concentration gradients, membrane permeability, and ion pumps are all associated with RMP

Lipid Bilayer

• The lipid bilayer forms the neuron's membrane
• It creates a barrier for ion separation, enabling voltage creation

Channels vs Pumps

• Channels facilitate passive ion flow based on concentration gradients
• Pumps use ATP to actively transport ions against their concentration gradients

Bernstein Membrane Theory

• Resting membrane potential arises from selective membrane permeability to K+
• Higher K+ concentration inside the cell generates an electrical potential

Passive Electrical Circuits

• A circuit with only a resistor and capacitor is passive because it lacks a voltage source or amplifiers
• It can only store energy, not generate it

Water/Electrical Analogy

• Voltage is analogous to water height, representing potential energy
• Electrical charge moves from high to low voltage, like water flows from high to low heights
• Changes in potential drive ion movement

Water as a Polar Solvent

• Water's polarity stabilizes Na+ and K+ ions, facilitating their transport through channels

Membrane Properties

• Permeability is the membrane’s ability to allow specific ions to pass through
• Resistance is the opposition to ionic current, determined by ion channels
• Capacitance is the ability of the membrane to store electrical charge
• Selectivity refers to channels transporting specific ions

Ion Concentration Gradients

• Ion concentration gradients lead ions to move across the membrane
• Unequal charge distribution creates voltage differences, i.e. the resting membrane potential

RMP Calculation

• Resting membrane potential is typically -65 mV to -70 mV
• There is more K+ inside the cell and more Na+ outside the cell
• Membrane is more permeable to K+ at rest due to K+ leak channels
• The sodium-potassium pump actively transports 3 Na+ out and 2 K+ in
• Each ion has its own equilibrium potential
• Use the Goldman-Hodgkin-Katz equation to calculate RMP

Nernst Equation

• E_ion = 2.303 RT/zF log ion_o/ion_i
• R is the gas constant
• T is the temperature in Kelvin
• z is the valence of the ion (electrical charge)
• F is Faraday’s constant
• ion_o is the concentration of the ion outside of the cell
• ion_i is the concentration of the ion inside of the cell

Equilibrium Potential

• Equilibrium potential for a specific ion is calculated using the Nernst equation
• Equilibrium potential is achieved when the concentration gradient is equal to the membrane potential

Ion Pumps

• Pumps transport 3 Na+ out and 2 K+ in against concentration gradients

Electrical Circuit Models

• A capacitor represents the membrane’s ability to store charge
• Resistors are ion channels that allow current flow

Electrochemical Equilibrium

• Electrochemical equilibrium occurs when there is no net movement of ions across the membrane
• At RMP, the membrane is permeable to K+ through leak channels so the membrane is close to K+ equilibrium

Forces Driving Equilibrium Potential

• Diffusion-concentration gradient: ions diffuse from areas of high concentration to low concentration
• Electrostatic force: opposite charges attract, like charges repel

RMP Generation and Maintenance

• Ion concentration gradients involve more K+ inside and more Na+ outside, maintained by the sodium-potassium pump
• Selective permeability refers to the membrane being more permeable to K+ because there are more K+ leak channels than Na+ channels
• Sodium-potassium pump actively transports 3 Na+ out and 2 K+ in, maintaining ion gradients

Membrane as Capacitor

• The neuronal membrane separates charges, storing electrical potential
• Membrane capacitance determines how quickly the membrane can respond to changes in voltage

Water/Electricity Analogy

• Voltage is like water pressure, the force driving flow
• Membrane capacitance is like a bucket, storing charge
• Ion channels are like a narrow pipe, limiting ion flow

Capacitance and Integration

• A capacitor integrates charge by storing it as voltage increases
• Larger capacitance results in slower voltage changes, affecting signal timing

Sodium-Potassium Pump

• The sodium-potassium pump maintains ion gradients by pumping 3 Na+ out and 2 Na+ in
• This process requires ATP because it goes against the concentration gradient

Nernst Equation

• The key components of the Nernst equation are R, T, F, and z
• Higher temperature or steeper concentration gradients increase the equilibrium potential

Goldman Equation

• Resting membrane potential is calculated using the Goldman equation, incorporating equilibrium potentials and permeabilities
• The Goldman equation is like multiple Nernst equations in one
• 58 log (P_K [K+]outside + P_Na [Na+]outside + P_Cl [Cl-]inside)/ (P_K [K+]inside + P_Na [Na+]inside + P_Cl [Cl-]outside)
• P is the permeability of the ion