The brain is an intricate network, consisting of approximately 200 billion neurons and more than a trillion glia Cells.

Each neuron receives and combines multiple inputs to determine, whether to transmit an action potential to the next target in its network (Neuron, Muscle, Gland, or Organ).

Three Main Components of the Central Nervous System

Neurons - basic signaling units of the nervous system.

Glial cells - or Neuroglia (nerve glue) are 10 times more common and account for more than half the brain’s volume. Provide support functions both chemically and structurally.

Vasculature

The Neuron Doctrine - Cajal

Connectional Specificity - cells are separate, and connections between cells are not random but pass information through specific pathways.

Dynamic Polarization - some parts of the neuron are specialized for taking information in, while others are specialized for sending it out.

Adapted from Kandel, E.R. Schwartz, J.H., and Jessell, T.M. (Eds.), Principles of Neural Science, 3rd edition. Norwalk, Connecticut: Appleton &

Lange, 1991. Copyright © 1991 by Appleton & Lange.

Variety of synapse possibilities

-Axodendritic-Axoaxonic-Axosomatic-Dendrodendritic

-Asymmetric (excitatory, glutamate or aspartate) -or Symmetric (inhibitory, GABA)

Excitatory Neurons

-Pyramidal Cells, projection -Spiny Stellate Cells, interneurons

Inhibitory Neurons

-Basket Cells, to somas and proximal dendrites, or shaft of apical dendrite, predominate layers III and V, horizontal inhibition-Chandelier Cells, synapse exclusively on the axon hillock of pyramidal cells, also known as axoaxonic cells, layer III, so may control corticocortical connections-Double Bouquet Cells, layers II, III, and V, association cortex, spines, columnar, limited horizontal spread

Summary - Neurons

-all neurological processes are dependent on complex cell-cell interactions between single neurons and/or groups of related neurons.

-Neurons can be described according to their size, shape, neurochemical characteristics, location, and connectivity.

-Structure and function are intimately related.

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Netter, F.H., The CIBA Collection of Medical Illustrations. Vol I: Nervous System, Part 1: Anatomy and Physiology.

Summit, NJ: CIBA Pharmaceutical Company, 1983. Adapted with permission of Novartis, formerly CIBA.

Subcellular Organization: Organelles and Their Functions

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SubCellular Anatomy

• Cell body (Soma) - the nucleus does not divide after maturity.

• Nucleus -enveloped compartment containing the genetic material of the cell.

• Nucleolus - site of gene transcription.

• Rough Endoplasmic Reticulum - extends throughout the cell for protein synthesis.

• Ribosomes - site of protein production.

• Smooth Endoplasmic Reticulum - tubular structure throughout the cell including nerve endings, site of the calcium pump and source of intracellular calcium, transportation of proteins.

• Golgi Apparatus or Complex - important for protein modification (e.g., GlycoProteins) and as a source of vesicles, i.e., packaging.

• Mitochondria - dispersed throughout the soma are part of oxidative phosphorylation coupling with electron transport, for ATP (energy) production; and may aid calcium concentrations at synapses, by high capacity low affinity transport.

• Axons - contain output microtubules (25 nm) composed of tubulin, and Neurofilaments (10 nm); important for axoplasmic transport (fast - 400 mm/day).

• Synaptic Vesicles - Neurotransmitter storage and release location.

• Dendrites - input microtubules important for plasticity of synapse formation.

• Synaptic Matrix - thickened cell membrane in region of synaptic transmission. Consists of extracellular matrix proteins.

Slow axonal transport

Fast axonal transport

Neurophysiology

Two types of synapses:Electrical (Gap Junctions)Chemical

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Contributors to the resting membrane potential:

1) Selective membrane permeability (ion channels, negative proteins)

2) Diffusion (equilibrium potential)3) Electrostatic Forces (equilibrium potential)4) Sodium-potassium pump (3 sodium ions out, 2 potassium in)

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-70 mV 0 mV

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1) Selective membrane permeability (ion channels, negative proteins)

2) Diffusion (equilibrium potential)3) Electrostatic Forces (equilibrium

potential)4) Sodium-potassium pump (3 sodium

ions out, 2 potassium in)

Contributors to the resting membrane potential:

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2.16A Adapted from Kandel, E.R. Schwartz, J.H., and Jessell, T.M.

(Eds.), Principles of Neural Science, 3rd edition. Norwalk, Connecticut: Appleton & Lange, 1991. Copyright © 1991 by Appleton & Lange.

2.16B Adapted from Kuffler, S., and Nicholls, J., From Neuron to Brain. Sunderland, MA: Sinauer Associates, 1976.

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Trigeminal Ganglion Cell: this is about 2 seconds of activity that was recorded from a ganglion cell after the maxillary (upper) incisor tooth of an anesthetized rat was tapped 5 times. Listen for 5 distinct "bursts" of action potentials.

Trigeminal Ganglion Cell: this is about 2 seconds of activity that was recorded from a rat ganglion cell after a single whisker (vibrissa) was moved and held in position. Listen for the rapid steady burst of action potentials. This neuron was firing about 100 action potentials every second.

Adapted from Kandel, E.R. Schwartz, J.H., and Jessell, T.M. (Eds.), Principles of Neural Science, 3rd edition. Norwalk, Connecticut:

Appleton & Lange, 1991. Copyright © 1991 by Appleton & Lange.

Ion Channels

- Ion channels are polypeptides, formed by amino acids, and any two amino acids can form a peptide, but many come to gather to form small and large proteins.

- Two main types, active transporters (Na+/K+ pump), and ion channels (gated and non-gated)

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Amino acid sequence - primary

Strings of amino acids coiled

into helical shape - secondary

Folding of helix can give rise to globular proteins - tertiary

Ion channel - complex 3-D structure made of globular proteins - quaternary

Doyle, D., Cabral, J., Pfuetzner, R., Kuo, A., Gulbis, J., Cohen, S., Chait, B., and MacKinnon, R., (1998). The structure of the potassium channel; Molecular basis of K+ conduction and selectivity; Science 280 (5360); 69-77.

2.26 Doyle, D., Cabral, J., Pfuetzner, R., Kuo, A., Gulbis, J., Cohen, S., Chait, B., and MacKinnon, R., (1998). The structure of the potassium

channel; Molecular basis of K?? conduction and selectivity; Science 280 (5360); 69-77.

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Receptors are specialized ion channels and can be directly or indirectly coupled

Direct - allows ions in, ionotropic

Indirect - secondary affect using G-proteins, second messengers, intracellular signaling, metabotropic receptors

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Adapted from Purves D., Augustine, G., and Fitzpatrick, D. (2001).

Neuroscience, 2nd edition. Sunderland, MA: Sinaur Associates.

Proteins

SG - synaptogamin

SB - synaptobrevin

ST - syntaxin

S25 - SNAP-25

Adapted from Purves D., Augustine, G., and Fitzpatrick, D. (2001).

Neuroscience, 2nd edition. Sunderland, MA: Sinaur Associates.

SG - synaptogamin, green

SB - synaptobrevin, blue

ST - syntaxin, red

S25 - SNAP-25, purple

Adapted from Purves D., Augustine, G., and Fitzpatrick, D. (2001).

Neuroscience, 2nd edition. Sunderland, MA: Sinaur Associates.

SG - synaptogamin, green

SB - synaptobrevin, blue

ST - syntaxin, red

S25 - SNAP-25, purple

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Cyclic Nucleotide Metabolism - cAMP SIGMA-ALDRICH