Neurons and Nervous System

Nervous System - Neurons

• Neurons transmit signals to specific target cells at synapses, controlling and coordinating the body along with the endocrine system
• Shape, size, and branching of neurons are extremely diverse
• The nervous system consists of all neurons in the body
• Signals travel through neurons at a very rapid rate (100 m/s)

Nervous System - Parts of Neurons

• Neurons have four parts: Dendrite, Cell Body, Axon and Presynaptic Terminals
• Dendrites receive input from other neurons via thousands of synaptic contacts
• Synaptic inputs can either inhibit or excite, increasing or decreasing likelihood of action potential
• The cell body integrates signals received through the dendrites
• Axons conduct and propagate action potentials
• Axon initial segment is typically where action potential initiation occurs
• Bundles of axons are called tracts in the central nervous system (CNS) and nerves in the peripheral nervous system (PNS)
• Presynaptic terminals output signals to another cell
• They release neurotransmitters to carry signals across the synapse
• Neurotransmitters bind to receptors on target cells, activating the cell

Nervous System - Types of Neurons

• Afferent neurons relay sensory signals to integrative centers of the central nervous system (CNS), including the brain and spinal cord
• Efferent neurons relay signals from the CNS to target cells that are under nervous control
• Interneurons are contained entirely within the CNS
• Neurons are classified by the number of processes emanating from the soma

Glial Cells

• Glial cells surround neurons
• The ratio of glial cells to neurons varies across animals, with more complex animals often having more glial cells per neuron.
• Schwann cells (in the PNS) and oligodendrocytes (in the CNS) envelop the axons
• Myelin sheath consists of multiple concentrically wrapped layers of glial membrane
• The myelin sheath insulates the axon and increases the velocity of action potential propagation
• Astrocytes regulate extracellular ion concentrations, supply metabolic substrates to neurons, and take up neurotransmitters.
• Microglial cells mediate immune responses and act as phagocytic cells

Nervous System - Circuits

• Nerves are organized into circuits
• A reflex is a simple, stereotyped behavioral response to a distinct stimulus
• Example of a startle response in cockroaches takes less than 150 milliseconds:
• Wind receptors detect air currents and sound waves
• A series of action potentials happen in sensory neurons located at the base of the hair
• Sensory neurons excite interneurons
• Interneurons excite leg motor neurons
• Leg motor neurons excite the extensor muscles of the leg

Nervous System - Resting Membrane Potential

• Resting membrane potential (Vm) refers to the normal electrical potential across the cell membrane of a cell at rest
• Most neurons measure between -40 mV and -60 mV
• The inner membrane surface is negative compared to the outer membrane surface
• Cells maintain higher concentrations of K+ and lower concentrations of Na+ and Cl- in the intracellular fluids compared to extracellular fluid
• Ion concentration differences are maintained by active transport (Na+-K+ pump) and passive diffusion

Nervous System - Equilibrium Potential

• Equilibrium potential refers to the membrane potential at which an ion species is at electrochemical equilibrium
• Concentration-diffusion forces are offset by electrical forces
• There is no net flux of that ion species across the membrane
• Ions are not at equilibrium potential inside the body
• K+ is constantly leaking out of the cell and Na+ is constantly leaking in

Nervous System - Pumps

• Na+-K+ pump is an electrogenic pump because it produces a voltage difference across the membrane which generates membrane potential
• Three Na+ ions are pumped for every two K+ ions
• Counteracts the diffusion of these ions through the cell membrane

Nervous System - Action Potential

• When nerves are stimulated, there is a local change in membrane potential right at the tiny portion of the cell
• This change is propagated through the neuron to carry the signal along the nerve
• Depolarization occurs when the inside of the cell becomes more positive
• Hyperpolarization occurs when the inside of the cell becomes more negative
• Action potential is a reversal of membrane potential from about -65 mV (inside-negative) to about +40 mV (inside-positive)
• Action potential lasts about 1 millisecond
• The resting membrane potential is then restored

Nervous System - Basic Action Potential Steps

• Membrane is locally depolarized past the voltage threshold that is required to trigger an action potential
• The membrane continues to become depolarized (rising phase) and the inside of the cell becomes more positive compared to the outside of the cell (overshoot)
• The inside of the cell is then repolarized during falling phase
• The cell briefly goes lower than resting membrane potential (undershoot) and then returns to resting membrane potential

Nervous System - Action Potential Responses

• Action potentials are all-or-nothing responses
• Action potential is triggered if the voltage threshold is reached
• Once action potentials are triggered, they propagate along the axon without losing strength
• Action potentials rely on voltage-gated ion channels whose opening depends on the membrane potential
• Leak channels allow ions to move down their electrochemical gradients and are always open

Nervous System - Steps of an Action Potential

• A stimulus depolarizes the membrane past threshold
• Voltage-gated Na+ channels open in response to the depolarization during the rising phase
• The membrane becomes much more permeable to Na+, which rushes into the cell and causes the inside of the cell to become more positive
• Voltage-gated Na+ channels are inactivated during the falling phase, making cells less permeable to Na+
• After a short delay, voltage-gated K+ channels are also opened, making the cell membrane much more permeable to K+ which rushes out of the cell down its gradient
• Voltage-gated K+ channels stay open for a few milliseconds during the recovery phase, causing a brief period of hyperpolarization
• Voltage-gated Na+ channels recover at the point and can now be opened again

Nervous System - Voltage Gated Sodium Channels

• The voltage-gated Na+ channel has four domains, each of which contain six membrane-spanning segments
• These four domains surround the pore and allow Na+ to move through the membrane
• Membrane-spanning segment 4 of each domain contains the voltage-sensor region
  • This region contains positively charged amino acids
• The P loop connects segments 5 and 6, lines the pore, and maintains the pore's selectivity for Na+
• The cytoplasmic loop between domains III and IV mediates the inactivation of the pore

Nervous System - Axons

• Action potentials are propagated down axons
• Axon action potential propagation is unidirectional because of the inactivation period of voltage-gated Na+ channels
• Inactivation of Na+ channels persists until the membrane potential returns to near its negative resting state
• Another reason for unidirectional propagation is hyperpolarization caused by the voltage-gated K+ channels

Nervous System - Refractory Periods

• Absolute refractory period is about ~1 ms after an action potential; the time during which it is not possible to generate another action potential in that location
• This is because voltage-gated Na+ channels are inactivated
• Relative refractory period lasts a few milliseconds after an action potential during which time it is harder to generate another action potential
• This is because the membrane is hyperpolarized due to voltage-gated K+ channels

Nervous System - Speed of Action Potential

• The speed of an action potential depends on axon diameter
• The greater the axon diameter, the faster the action potential will propagate
• Myelinated axons propagate action potentials faster than non-myelinated axons
• Nodes of Ranvier are gaps in the glial wrapping of the cell; in myelinated axons this is the only area where action potentials can occur
• These cells exhibit saltatory conduction, enabling action potential jumps from node to node
• Temperature also affects speed, with higher temperatures result in faster propagation of action potentials