Neurophysiology: Cells and Structure

• Neurophysiology involves studying the function of the nervous system
• It uses biophysics, molecular biology, and anatomy techniques
• To understand the electrical and chemical processes of neuronal signaling and behavior

Cells of the Nervous System

• Neurons are primary units for signaling
• Glial cells support the function of neurons

Neurons

• Neurons specialize in electrical and chemical signals
• Neurons utilize unique structures to transmit information rapidly and precisely

Neuron Doctrine

• The neuron is the fundamental unit of the nervous system (structural and functional)
• Neurons are discrete, not continuous cells
• Neurons include the cell body (soma), dendrites, and axon
• Synapses transmit signals via chemical messengers

Neuron Structure

• Soma contains the nucleus and organelles
• Dendrites are branching extensions that receive signals
• Axon is a single extension that transmits signals
• The axon hillock is where signals are generated
• Myelin sheath insulates the axon, increasing signal speed
• Nodes of Ranvier are gaps in the myelin sheath exposing the axon
• Axon terminals are specialized endings that release neurotransmitters

Types of Neurons

• Sensory neurons transmit information from receptors to the central nervous system (afferent)
• Motor neurons transmit information from the central nervous system to muscles/glands (efferent)
• Interneurons connect sensory and motor neurons in the central nervous system, mediating reflexes and higher-order processing

Glial Cells

• Glial cells support neurons structurally and metabolically
• Types of glial cells: astrocytes, oligodendrocytes, microglia, and Schwann cells

Astrocytes

• Most abundant glial cells in the brain
• Regulate the chemical environment by removing excess neurotransmitters and ions
• Provide metabolic support by supplying nutrients
• Contribute to the blood-brain barrier

Oligodendrocytes

• Form the myelin sheath around CNS axons
• One oligodendrocyte myelinates multiple axons

Microglia

• Immune cells of the central nervous system
• Remove debris and pathogens through phagocytosis
• Release cytokines and other signaling molecules for inflammation and immune responses

Schwann Cells

• Form the myelin sheath around PNS axons
• One Schwann cell myelinates a single axon

Electrical Signals in Neurons

• Neurons use electrical signals for transmitting information
• These signals result from ion flow changes across the neuron's cell membrane

Membrane Potential

• The membrane potential is the electrical charge difference inside versus outside the cell
• It is typically negative at rest

Resting Membrane Potential

• The resting membrane potential is the stable potential of a non-signaling neuron
• It is typically around -70 mV
• Maintained by unequal ion distribution (Na+, K+, Cl-, A-)
• The sodium-potassium pump (Na+/K+ ATPase) maintains concentration gradients by transporting Na+ out and K+ into the cell
• Ion channels allow selective ion movement, contributing to the membrane potential

Ion Channels

• Ion channels are transmembrane proteins that allow specific ions to flow
• Types of ion channels: voltage-gated, ligand-gated, or mechanically gated

Voltage-Gated Channels

• Voltage-gated channels open/close in response to membrane potential changes

Ligand-Gated Channels

• Ligand-gated channels open/close in response to neurotransmitter or signaling molecule binding

Mechanically-Gated Channels

• Mechanically-gated channels open/close in response to cell membrane deformation

Nernst Equation

• The Nernst equation calculates the equilibrium potential for an ion
• Based on its concentration gradient, determining each ion's contribution to resting membrane potential

Goldman-Hodgkin-Katz (GHK) Equation

• The GHK equation calculates membrane potential using permeability and concentration gradients of multiple ions
• It is a more comprehensive model than the Nernst equation

Action Potentials

• Action potentials are rapid, transient changes in membrane potential
• They travel along the axon
• They are the primary means of long-distance communication in the nervous system

Action Potential Generation

• When the membrane potential reaches a threshold (around -55 mV), voltage-gated Na+ channels open
• This causes a rapid Na+ influx, depolarizing the membrane
• Voltage-gated K+ channels then open, allowing K+ to flow out
• K+ efflux repolarizes the membrane
• Voltage-gated Na+ channels inactivate shortly after opening
• The membrane potential may briefly hyperpolarize due to continued K+ efflux
• The Na+/K+ ATPase restores ion gradients

Action Potential Propagation

• Action potentials propagate along the axon without decrement
• The influx of Na+ depolarizes adjacent regions, triggering more voltage-gated Na+ channels to open
• This continues down the axon

Refractory Period

• After an action potential, there is a brief refractory period
• The absolute refractory period: no stimulus can generate another action potential due to inactivated Na+ channels
• The relative refractory period: a stronger stimulus is required due to persistent K+ efflux and inactivated Na+ channels

Myelination and Saltatory Conduction

• In myelinated axons, action potentials "jump" from one node of Ranvier to the next
• This process is called saltatory conduction
• Myelination increases speed by reducing capacitance and increasing membrane resistance

Synaptic Transmission

• Synaptic transmission is the process by which neurons communicate at synapses
• Synapses are specialized junctions
• There are two main types: chemical and electrical

Chemical Synapses

• Chemical synapses use neurotransmitters for signal transmission
• The presynaptic neuron releases neurotransmitters into the synaptic cleft
• These neurotransmitters bind to receptors on the postsynaptic neuron

Neurotransmitter Release

• When an action potential reaches the axon terminal, voltage-gated Ca2+ channels open
• Ca2+ influx triggers neurotransmitter-containing vesicles to fuse with the presynaptic membrane
• Neurotransmitters are released into the synaptic cleft by exocytosis

Neurotransmitter Binding

• Neurotransmitters diffuse across the synaptic cleft and bind to postsynaptic receptors
• Receptors can be ionotropic (ligand-gated ion channels) or metabotropic (G protein-coupled receptors)

Ionotropic Receptors

• Ionotropic receptors are ligand-gated ion channels
• These receptors open/close upon neurotransmitter binding
• They mediate fast synaptic transmission

Metabotropic Receptors

• Metabotropic receptors are G protein-coupled receptors
• They activate intracellular signaling pathways upon neurotransmitter binding
• They mediate slower, longer-lasting synaptic transmission

Postsynaptic Potentials

• Neurotransmitter binding causes changes in the postsynaptic membrane potential
• Excitatory postsynaptic potentials (EPSPs) depolarize the membrane, increasing the likelihood of an action potential
• Inhibitory postsynaptic potentials (IPSPs) hyperpolarize the membrane, decreasing the likelihood of an action potential

Neurotransmitter Removal

• Neurotransmitters are removed from the synaptic cleft by:
  • Reuptake into the presynaptic neuron or glial cells
  • Enzymatic degradation
  • Diffusion away from the synapse

Electrical Synapses

• Electrical synapses use gap junctions to connect cytoplasm between two neurons directly
• Ions and small molecules flow directly from one neuron to another
• Electrical synapses mediate very fast transmission

Synaptic Integration

• Synaptic integration is the summation of synaptic inputs to determine action potential firing
• Temporal summation occurs when multiple EPSPs/IPSPs occur rapidly at the same synapse
• Spatial summation occurs when EPSPs/IPSPs occur simultaneously at different synapses

Neurotransmitters

• Neurotransmitters are chemical messengers for transmitting signals from one neuron to another
• Examples: acetylcholine, glutamate, GABA, dopamine, norepinephrine, and serotonin

Acetylcholine

• Acetylcholine is a neurotransmitter involved in muscle contraction, learning, and memory

Glutamate

• Glutamate is the primary excitatory neurotransmitter in the brain

GABA

• GABA is the primary inhibitory neurotransmitter in the brain

Dopamine

• Dopamine is a neurotransmitter involved in reward, motivation, and motor control

Norepinephrine

• Norepinephrine is a neurotransmitter involved in arousal, attention, and stress responses

Serotonin

• Serotonin is a neurotransmitter involved in mood, sleep, and appetite