lecture 4

Functional Anatomy of Nerve Cells

Nerve Cells: Signaling Units of the Brain

• Nerve cells exhibit considerable variability, but their anatomical organization is paramount.
• Pertinent variable factors include:
  • Structural components of individual nerve cells.
  • Mechanisms by which neurons produce signals.
  • Patterns of connection.
  • Relationship of different patterns of interconnection to different behaviors.
  • Cellular and circuit modification by experience.

Two Classes of Cells in the Nervous System

• Neurons: Functional basic units.
  • Possess dendrites and axons.
• Glia: Support cells.
  • Include microglia, oligodendrocytes, Schwann cells, and astrocytes.

Glial Cell Functions

• Astrocytes: Cleaning and neuron function assistance.
• Microglia: Immune support.
• Oligodendrocytes: Myelin sheath formation in the central nervous system (CNS).
• Schwann cells: Myelin sheath formation in the peripheral nervous system (PNS).

Neuron Structure and Function

• Key Components:
  • Dendrites: Receive signals; apical and basal dendrites.
  • Cell Body (Soma): Contains the nucleus.
  • Axon: Conducts nerve impulses.
    • Axon Hillock: Where action potentials are formally generated; high density of voltage-gated $Na^+$ channels.
    • Axon Initial Segment (AIS): Responsible for action potential initiation.
    • Myelin Sheath: Insulation around the axon.
    • Nodes of Ranvier: Gaps in the myelin sheath.
  • Synapse: Communication site between two neurons.
    • Presynaptic Terminal: Contains synaptic vesicles and calcium ion channels.
    • Synaptic Cleft: Space between neurons.
    • Postsynaptic Dendrite: Contains ion channels with receptor sites.
• Action Potential (AP): Driven by $Na^+$ channels.
• Summation: Multiple signals converge.

Major Anatomical Classifications of Neurons

• Unipolar Cell:
  • Axon with terminals.
• Bipolar Cell:
  • Specialized sensory neurons (e.g., bipolar cell of retina).
  • Dendrites and axon.
• Pseudo-Unipolar Cell:
  • Sensory neurons for physical touch.
  • Single bifurcated process with peripheral axon towards the skin and muscle, and a central axon towards the spinal cord.
• Multipolar Cells:
  • Motor neuron of spinal cord.
  • Pyramidal cell of hippocampus with apical and basal dendrites and lots of dendritic spines.
  • Purkinje cell of cerebellum with a dendritic arbor.

Three Major Functional Categories of Neurons

• Afferent Neurons (Sensory):
  • Receiving signal, take signal to CNS (spinal cord).
• Efferent Neurons (Motor):
  • Sending signal from CNS.
• Interneurons:
  • Everything else; reflexes occur all in spinal cord.

Subdivisions of Functional Categories

• Divided by dendritic field size and complexity.
  • Midget, Parasol, Large sparse, Giant sparse, Broad thorny, Narrow thorny, Small, Large.
• Position of dendrites in inner plexiform layer.
  • Monostratified, Bistratified, Multiple sets of dendrites.
  • All retinal neurons.

Glial Cells: Neuronal Support

• Peripheral Nervous System:
  • Satellite cells: Form casings and provide protection.
  • Schwann cells: Form myelin sheaths (1 cell makes 1 myelin sheath); insulation prevents leaks.
• Central Nervous System:
  • Ependymal cells: Produce cerebrospinal fluid (CSF) through the choroid plexus; provide protection and buoyancy; no axons/dendrites and no action potentials).
  • Oligodendrocytes: Form myelin sheaths (one cell can make many myelin sheaths).
  • Astrocytes: Wrap in blood-brain capillaries; very electrically active but no action potentials produced; most similar to neurons; no nuclei.
  • Microglia: Immune system function.

Neural Circuits and Glia

• Each nerve cell is part of a circuit that mediates specific behaviors and are supported by glia.
• Stretch-Reflex Circuit:
  • Requires at least 4 neurons to check for basic neuronal function.
  • Stimulus: Stretch receptor (ion channel physically opened).
  • Quadriceps (extensor) muscle is stretched.
  • Hamstring (flexor) Muscle gets inhibited
  • Sensory neuron bifurcates (splits into 2).
  • Extensor motor neuron (activated).
  • Flexor motor neuron (inhibited).
  • Inhibitory interneuron.
  • Ventral and dorsal horn in spinal cord.

Diverging and Converging Neuronal Connections

• Divergence:
  • One input affects multiple neurons.
• Convergence:
  • Multiple inputs converge on one neuron; mostly input (afferent).

Inhibitory Interneurons

• Produce either feedforward or feedback inhibition.
• Feedforward Inhibition:
  • Inhibiting downstream.
  • Afferent neurons innervating extensor muscles and flexor muscles.
  • Enhances desired output.
• Feedback Inhibition:
  • Negative feedback.
  • Prevents overfiring.
  • Axon collateral.
  • Seizures are unmitigated firing.

Signaling Organization in Neurons

• Four functional regions: Input, Integrative, Conductive, Output
  • Dendrites are also integration site for synapse.
  • Axon hillock & AIS are the integrative region of the neuron.
  • Axon is the conductive region

Ion Distribution and Electrical Currents

• Neurons are batteries that store energy in the form of ion gradients and electrical potentials across the cell surface membrane.
• Ion pumps transport ions against their concentration gradients to create ion gradients (batteries).
• Pumps are driven by energy from ATP hydrolysis.
• Electrical currents are generated by the opening of ion-selective channels, allowing flow of current as ions down their concentration and electrical potential gradients.
• $[Na^+]<em>i = 5 \, mM$; $[Na^+]</em>o = 130 \, mM$
• $[K^+]<em>i = 130 \, mM$; $[K^+]</em>o = 5 \, mM$

Neuronal Signaling and Electrical Potential Differences

• $Na^+$ concentrated outside of cell (ECF).
• $K^+$ concentrated inside cell (ICF).
• Neuronal signaling is based on electrical potential differences generated by the movement of ions. (Equilibrium)
• ECF: $Na^+$ = 145 mEq/L, $K^+$ = 4 mEq/L
• ICF: $Na^+$ = 12 mEq/L, $K^+$ = 150 mEq/L

Ion Flow Across the Membrane at Resting Potential

• At steady state: $I<em>K + I</em>{Na} + I_{Cl} = 0$
• $V_m = -72.4 \, mV$
• $E<em>K = -82.1 \, mV$; $g</em>K = 2 \, nS$; $I<em>K = 19.4 \, pA$; $R</em>K = 0.5 \, G\Omega$
• $E<em>{Na} = +84.8 \, mV$; $g</em>{Na} = 0.1 \, nS$; $I<em>{Na} = -15.7 \, pA$; $R</em>{Na} = 10 \, G\Omega$
• $E<em>{Cl} = -63.6 \, mV$; $g</em>{Cl} = 0.4 \, nS$; $I<em>{Cl} = -3.5 \, pA$; $R</em>{Cl} = 2.5 \, G\Omega$
• $E<em>K + I</em>K R<em>K = V</em>m = E<em>{Na} + I</em>{Na} R<em>{Na} = E</em>{Cl} + I<em>{Cl} R</em>{Cl}$
• $-82.1 \, mV + (19.4 \, pA)(0.5 \, G\Omega) = -72.4 \, mV = +84.8 \, mV + (-15.7 \, pA)(10 \, G\Omega) = -63.6 \, mV + (-3.5 \, pA)(2.5 \, G\Omega)$

Neuronal Signaling and Ion Movement

• Neuronal signaling is based on electrical potential differences generated by the movement of ions.
• Ligand binds to receptor on dendrites or soma, triggering current.
• $Na^+$ influx occurs across the plasma membrane of the dendrite.
• Trigger zone initiates the signal.

Action Potentials

• Characteristics of action potential (unlike local potential):
  • Follows an all-or-none law: If threshold is reached, neuron fires at its maximum voltage. If threshold is not reached, it does not fire.
  • Nondecremental: Does not get weaker with distance.
  • Irreversible: Once started, goes to completion and cannot be stopped.

Components and Signals

• The input component produces graded local signals generated by specialized receptors.
• Passive and degrade. Always happen
• No refractory period
  • Stretch
  • Muscle spindle
  • Trigger zone
  • Myelinated axon
  • Sensory neuron cell body
  • Synaptic terminal

Comparison of Local (Passive) and Propagated Signals

• Local (passive) signals decay.

Transformation of Neural Signal from Sensory to Motor

Molecular Differences in Nerve Cells

• Nerve cells differ most at the molecular level.
• Differences occur at layer position, morphology, connectivity, physiology, and gene expression.

Neural Circuits and Experience

• Neural circuits can be modified by experience.
• Neuronal plasticity is the basis of learning and memory.
• Experience changes the strength of synaptic connections.