Neurons and Glial Cells

• Nervous systems are composed of two cell categories:
  • Neurons (or nerve cells): Excitable cells that generate and transmit electrical signals (action potentials).
  • Glia (or glial cells): Support cells that maintain the extracellular environment.

Structure of a Typical Neuron

• Dendrites receive information from other neurons.
• The cell body contains the nucleus and most cell organelles.
• Information collected by dendrites is integrated in the axon hillock, which generates action potentials.
• The axon conducts action potentials away from the cell body.
• Axon terminals synapse with a target cell.

Neuron Diversity

• Neurons exhibit a variety of forms.
• Bushy dendrites collect information from many other cells.
• Some neurons branch over a broad area.
• Neurons can communicate over long distances via long axons.
• Neurons with fewer dendrites process fewer inputs.

Macroglia Types and Functions

• Oligodendrocytes in the CNS produce myelin and insulate axons.
• Schwann cells insulate axons in the PNS.
• Astrocytes contribute to the blood-brain barrier, protecting the brain.
• Microglia provide the CNS with immune defenses.

Demyelinating Disease: Multiple Sclerosis

• One of the most common demyelinating diseases is multiple sclerosis.

Electrical Signals in Neurons

• Ion channels and ion transporters in the membrane create membrane, resting, and action potentials.
• Membrane potential refers to the charge difference across the membrane, with the inside of the cell negative relative to the outside.
• Resting potential is the steady-state membrane potential of a resting neuron.
• An action potential (or nerve impulse) is a rapid, large change in membrane potential.
• Action potentials are generated by the opening and closing of ion channels.
• Voltage is a force that causes electrically charged particles (ions) to move across cell membranes.
• Major ions in neurons include sodium (Na+), potassium (K+), calcium (Ca2+), and chloride (Cl-).

Measuring Membrane Potential

• Membrane potential can be measured using electrodes inside and outside the neuron.
• In an unstimulated neuron, a constant difference of -60 mV between outside and inside is the resting potential.

Sodium-Potassium Pump

• The sodium-potassium pump moves Na+ ions from inside and exchanges them for K+ from outside, establishing concentration gradients.
• The Na+-K+ pump is an antiporter (sodium-potassium ATPase) that requires ATP.

Ion Channels

• Ion channels in the membrane are selective and allow some ions to pass more easily.
• The direction and size of ion movement depend on the concentration gradient and the voltage difference of the membrane.
• Two forces acting on an ion define its electrochemical gradient.
• Potassium channels are open in the resting membrane and are highly permeable to K+ ions.
• K+ ions diffuse out of the cell along the concentration gradient, leaving behind negative charges within the cell.
• K+ ions diffuse back into the cell due to the negative electrical potential.
• The potassium equilibrium potential is the membrane potential at which the net movement of K+ ceases.

Equations for Membrane Potential

• The Nernst equation calculates membrane potential when only one type of ion can cross a membrane that separates solutions with different concentrations of that ion.
• Squid axons are used to measure ion concentrations inside and outside a neuron.
• The Goldman (Hodgkin-Katz) equation describes equilibrium membrane potential, taking into account the relative permeabilities of multiple ions.

Studying Ion Channels

• Patch clamping is a technique used to study ion channels.

Gated Ion Channels

• Gated ion channels open and close under certain conditions.
  • Voltage-gated channels respond to changes in voltage across the membrane.
  • Chemically-gated channels depend on molecules that bind or alter channel protein.
  • Mechanically-gated channels respond to force applied to the membrane.

Membrane Potential Changes

• Leak K+ channels create the resting potential; gated channels are closed.
• Some voltage-gated Na+ channels open, depolarizing the cell to threshold.
• Additional voltage-gated Na+ channel activation gates open, causing a rapid spike of depolarization—an action potential.
• Na+ channel inactivation gates close; gated K+ channels open, repolarizing and even hyperpolarizing the cell.
• All gated channels close, and the cell returns to its resting potential.
• Graded membrane potentials are changes from the resting potential; graded potentials can transmit signals over very short distances (local changes only).
• They are important in neuromuscular junctions, the sensory system, and the generation of action potentials.

Action Potential Course

• Resting potential
• Threshold
• Depolarization
• Depolarization
• After-hyperpolarization

Signal Transmission

• Voltage-gated Na+ channels cannot open during the refractory period.
• Action potentials travel along axons without loss of signal.
• Action potentials are all-or-none, self-regenerating, and orthodromic.
• In myelinated axons, APs jump from node to node, resulting in saltatory conduction.
  • Myelinated axons offer faster conduction compared to the slower conduction in unmyelinated axons.
  • Propagation of action potential is increased in larger diameter axons (vs smaller).
  • Propagation of action potential is increased in myelinated vs non-myelinated axons.

Synapses

• Neurons communicate with other neurons or target cells at synapses.
• In a chemical synapse, chemicals released from a presynaptic cell induce changes in a postsynaptic cell.
• In an electrical synapse, the action potential spreads directly to the postsynaptic cell.
• Electrical synapses couple neurons electrically through gap junctions, which consist of 6 subunits, each with 4 transmembrane domains.
• Molecules under 1 kDa are freely diffuse.

Electrical vs Chemical Synapses

• Electrical synapses transmit signals with direction, velocity of transmission, and width of synaptic cleft.
• Chemical synapses transmit signals with possibility of IPSPs, and presence of synaptic vesicles.
• Electrical synapses in vertebrates are less common than chemical synapses.
• Electrical synapses do not allow temporal summation, require a large area of contact between the membranes and cannot be inhibitory.

Neuromuscular Junction

• The neuromuscular junction is a chemical synapse between motor neurons and skeletal muscle cells.
• Chemical synaptic transmission begins with the arrival of an action potential.
• ACh receptor is a ligand-gated, non-selective cationic channels
• Synaptic function involves proteins related to Vesicle formation, Transport of NTs into vesicles, Anchoring of vesicles, Docking of vesicles, Fusion of vesicular and cell membranes, Endocytosis of vesicles membrane for recycling, all of which are impacted by botulinum & tetanus

Neural Signals

• The postsynaptic cell sums the excitatory and inhibitory inputs.
  • EPSP--excitatory synapse
  • IPSP--inhibitory synapse
• Neural signals spread to the axon hillock by local current flow
• Postsynaptic potentials are summed over space and time.
  • Spatial summation occurs when several excitatory postsynaptic potentials (EPSPs) arrive at the axon hillock simultaneously.
  • Temporal summation means that postsynaptic potentials created at the same synapse in rapid succession can be summed.

Neurotransmitters

• The action of a neurotransmitter depends on the receptor to which it binds.
• Ionotropic receptors are ion channels with fast, short-lived responses (e.g., glutamate receptors, GABAA, and glycine receptors).
• Metabotropic receptors are not ion channels, initiate signaling cascades and offer slower, longer-lived responses (e.g., glutamate receptor, GABABreceptors).
• Each neurotransmitter has multiple receptor types, eg ACh has two:
  • Nicotinic receptors are ionotropic and mainly excitatory. -Muscarinic receptors are metabotropic and mainly inhibitory.
• Ionotropic glutamate receptors are divided into classes. -NMDA
• AMPA
• Neurotransmitters are cleared from the cleft after release. -Diffusion. -Reuptake by adjacent cells.
• Enzymes destroy neurotransmitters.
• Drugs can act on the nervous system by modulating synaptic interactions, for example: -Agonists mimic or potentiate the effect and block pain. -Antagonists block the actions

Neural Organization

• The central nervous system (CNS) consists of cells found in the brain and spinal cord.
• The peripheral nervous system (PNS) consists of neurons and support cells found outside the CNS.
• Neurons are organized into neural networks.
  • Afferent neurons carry sensory information. -Efferent neurons carry commands and effectors
• Effector stores and communicates between neurons.
• The multiple synapse pathway involving a spinal interneuron inhibits firing in the motor neuron for the antagonistic muscle.
• Brains Vary in Size and Complexity.