Neuron Structure and Function

• First cells in nervous system signaling were choanocytes, lining interior spaces in simple basal animals like sponges.
• Sponge choanocytes express vertebrate post-synaptic genes; neuroid cells express pre-synaptic genes.
• Two cell types communicate with the glutamate neurotransmitter.
• Synaptic signaling gene networks are evolutionarily old.
• Nervous system complexity progressed from simple nerve nets to centralized systems in vertebrates.

Structure and Maintenance of Neurons

• The nervous system has two main divisions: the central nervous system (CNS) and the peripheral nervous system (PNS).
• The CNS consists of the brain and spinal cord.
• The PNS connects the brain and spinal cord with muscles, sense organs and glands.
• Neurons are specialized cells and the functional units of the nervous system.
• Neurons generate electrical signals called action potentials (APs).
• Electrical signals trigger neurotransmitter release at chemical synapses for cell communication in most neurons.
• Glial cells are non-neuronal cells that support neurons, but do not generate action potentials.

Neuron Structure

• The cell body contains the nucleus.
• Dendrites receive information from neurotransmitters.
• The axon carries outgoing APs to target cells.
• The axon hillock, arising from cell body, generates APs.
• The axon terminal (synaptic knob), at the end of each branch, releases neurotransmitters.

Transport Through the Axon

• Axonal transport occurs along microtubule frameworks via motor proteins.
• Kinesin moves from the cell body toward the axon, transporting nutrients, mitochondria, and secretory vesicles (anterograde transport).
• Dynein moves backward, from axon terminals to the cell body, transporting recycled growth factors, vesicles, and pathogens (retrograde transport).

Classes of Neurons

• Afferent neurons carry information from peripheral receptors to the CNS, with the cell body in the PNS and a split axon.
• Efferent neurons carry information from the CNS to effector cells in the periphery, possessing a cell body with multiple dendrites.
• Interneurons, comprising 99% of all neurons, are entirely in the CNS and integrate afferent and efferent signals.
• Nerves are bundles of multiple PNS axons and connective tissues transmitting action potentials.

Synapses

• Synapses are interfaces between neurons and can be electrical or chemical.
• Electrical synapses connect two neurons via gap junctions, allowing direct AP passage.
• Chemical synapses involve neurotransmitter release from the presynaptic cell into the synaptic cleft, binding to postsynaptic cell receptors in response to an AP.
• Chemical synapses can either promote or inhibit APs in the postsynaptic cell.

Types of Glial Cells

• In the PNS, Schwann cells produce myelin sheaths around axons.
• In the CNS, astrocytes regulate extracellular fluid composition, stimulate tight junction formation, and metabolically sustain neurons.
• Microglia perform immune functions and contribute to synapse remodeling and plasticity.
• Ependymal cells regulate cerebrospinal fluid production and flow.
• Oligodendrocytes form the myelin sheath around CNS axons.

Function of Myelin

• Myelin acts as an electrical insulator preventing ion crossing and electrical current flow.
• Nodes of Ranvier are gaps between myelin sheaths allowing Na+ and K+ ion exchange.
• Action potentials jump between Nodes of Ranvier through the process of saltatory conduction, speeding up conduction and conserving energy.
• Myelinated fibers can be thinner and achieve the same conduction speed, saving space.

Growth and Development of the Nervous System

• Stem cells can produce neurons or glial cells to form the nervous system.
• Growth cones form at the end of extending axons.
• Glial cells guide extending axons.
• Alcohol, drugs, malnutrition, and viruses can permanently damage the developing nervous system.
• Neuronal plasticity decreases with age.
• Axon regeneration can occur in the PNS if the cell body is unaffected by damage.
• Spinal injuries often lead to oligodendrocyte apoptosis, causing myelin sheath loss.

Regeneration

• There is no significant axon regeneration within the CNS.
• Other vertebrates can regenerate within the CNS, but mammals have lost this capacity.
• The potential lack of CNS regeneration guards against uncontrolled infections.

Resting Membrane Potential

• Resting membrane potential is the potential difference across a neuron's plasma membrane at rest without an action potential.
• The inside of neurons is negative compared to the outside, approximately -40 to -90 millivolts (-70 mV on average).
• Ion movement causes changes in membrane potential.
• Na+ and Cl- concentrations are higher in extracellular fluid, while K+ concentration is higher in intracellular fluid.

Magnitude Depends on

• Specific ion concentrations in intracellular vs. extracellular fluid
• Membrane permeability to these ions
• Electrochemical gradient

Equilibrium Potential

• Electrochemical gradient can be found by Nernst Equation
• Equation helps understand general ion concentration patterns.
• Resting membrane potential depends on ion concentration gradients and membrane permeability, per the Goldman-Hodgkin-Katz equation.
• The cell membrane is usually ~ -70 mV.
• The resting potential is closer to the K+ equilibrium because the membrane is more permeable to K+ than Na+ at rest at rest.
• Electrical and concentration gradients favor Na+ movement into the cell.

Resting Membrane Potential Steps

• The Na+/K+ ATPase pump establishes Na+ and K+ concentration gradients (3 Na+ out, 2 K+ in).
• The membrane is more permeable to K+, so the flux of K+ is greater than Na+
• The concentration gradients determines the equilibrium potentials for the ions.
• A higher permeability for K+, and a greater electrochemical gradient for Na+.

Graded Potentials

• Graded potentials are changes in membrane potential localized to a small plasma membrane region.
• These potentials vary in magnitude with stimulus strength and lack a threshold.
• Graded potentials can be summed and decrease in strength with distance (decremental).
• They can be depolarizing or hyperpolarizing, initiated by a stimulus at a receptor or neurotransmitter binding, and depend on ligand or mechanically gated ion channels.

Types of Graded Potentials

• Synaptic potentials, either excitatory (EPSP) or inhibitory (IPSP), are produced in a postsynaptic neuron due to neurotransmitter release from a presynaptic terminal
• Receptor potentials are generated at peripheral afferent neuron endings in response to a stimulus.
• Pacemaker potentials occur spontaneously in specialized pacemaker cells.

Action Potentials

• Action potentials are large and rapid depolarizations (up to 100 mV) of the membrane, used for long-distance signaling.
• They exhibit a threshold, are all-or-none and are non-decremental.
• Information about stimulus strength is indicated by the frequency, not magnitude, of action potentials.
• Graded potentials trigger action potentials once they reach the threshold.
• Excitability depends on generating action potentials.

Voltage Gated Channels

• Are key for generating APs.
• Na+ and K+ ion channels contain charged amino acid residues that respond to membrane potential changes.
• Na+ channels open and inactivate more rapidly than K+ channels.

Action Potential Steps

• The resting membrane potential is close to the K+ equilibrium potential, at ~ -70 mV.
• Depolarization stimulus brings the membrane to a critical threshold potential to initiate action potential.
• Voltage-gated Na+ ion channels open, leading to rapid depolarization as Na+ flows into the cell and creates a positive feedback loop.
• As membrane potential peaks, Na+ permeability declines due to inactivation gates blocking feedback.
• K+ outflow leads to rapid repolarization and return to the resting value.
• Return to a negative membrane potential causes Na+ channels to reset.
• K+ channels close slowly, causing a period of hyperpolarization.
• K+ channels close, completing membrane potential restoration through negative feedback.

Refractory Periods

• Absolute refractory period means a second action potential cannot be generated, as Na+ channels are open or inactivated.
• Relative refractory period is when a subsequent potential can be produced if the stimulus is much higher.
• Limit number of APs.
• Contribute to separation of electrical signals
• Determine AP propagation direction

Influencing Factors

• Myelination leads to saltatory propagation and is faster than in nonmyelinated axons.
• Larger fiber diameters increase propagation speed, meaning myelination adds speed and saves space.

Action Potentials

• Convergence is when neural input from several neurons affects a single receiving neuron.
• Divergence is when a single neuron has axon branches that affect many receiving neurons.

Drugs and Toxins

• Local anesthetics block voltage-gated Na+ channels, preventing AP generation.
• Graded potentials are generated, but pain signals sent to brain don't exist.
• The neurotoxin tetrodotoxin blocks voltage-gated Na+ channels, which can be lethal.

Synapses Types

• Electrical: Presynaptic cell connects to postsynaptic cell via gap junctions, allowing AP flow.
• Chemical: Transmitters released from axon terminals, which bind to receptors and other postsynaptic neurons.

Chemical Signalling

• Neurotransmitters stored in synaptic vesicles in axon terminals
• Depolarization causes Ca2+ channels to open, and Ca2+ flows into the axon terminal when an action potential arrives.
• Neurotransmitters are released via exocytosis
• Neurotransmitters bind to receptors on the postsynaptic cell.
• They are removed from the synaptic cleft by degradation.

Activation of the Postsynaptic Cell

• Excitatory Postsynaptic Potentials (EPSP)-depolarization, brings membrane potential closer to threshold
• Inhibitory Postsynaptic Potential (IPSP)-hyperpolarization, membrane potential becomes more negative and is farther from the threshold.
• Ions open that allow Na+ cross
• K+ channels hyperpolarizes membrane potential

Summation and Factors

• Temporal is when Graded potentials occur together in time a synapse are summed
• Spatial summation is when graded potentials generate are summed
• Ca2+ results in release after neurotransmitters.
• Autoreceptors on presynaptic leads binding
• Effects of neurotransmitters or neuromodulators acting on postsynaptic neuron

Types of Receptors for Neurotransmitters

• Binding of neurotransmitter directly opens ion channels within the receptor.
• Signaling binds neurotransmitters

Neurotransmitters and Neuromodulators

• Neurotransmitters are involved in rapid communication.
• They bind to open channels produce EPSPs or IPSPs, which excite.

Important Neurotransmitters

• Acetylcholine is in the brain and PNS's neuromuscular junctions.
• There are 2 two receptors
• Degraded via the enzyme acetylcholinesterase, found on presynaptic and postsynaptic membranes.
• Nerve gas causes buildup, leads to deaths etc

Biogenic Amines

• Small and charged.
• Includes catecholamines
• Catecholamines are from tyrosine
• Serotonin acts mainly as affects mood and behavior

Amino acid

• Primary excitatory in CNS
• Glutamate is excitatory and NMDA receptors example of long term

Intrinsic

• GABA is major
• Glycine

Neuropeptides

• Are often co-secreted
• Examples are endogenous and synthetic opioids used for analgesics

Gases

• Can serve as neuromodulators

Purines

= Nontraditional as act as neuromodulators

Lipids

Act mainly as neuromodulators

Neuroeffector

• Events are similar to at synapses between neurons
• Receptors may be ionotropic or metabotropic

Multiple sclerosis

• Involves attack on myelin, leads to deficits in nervous function