Transcript Lecture 2

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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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)
absolute refractory period versus refractory period
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)
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
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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 Gproteins, second
messengers,
intracellular signaling,
metabotropic receptors
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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.
W. W. Norton
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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
Adapted from Purves D., Augustine, G., and Fitzpatrick, D. (2001).
Neuroscience, 2nd edition. Sunderland, MA: Sinaur Associates.
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Cyclic Nucleotide Metabolism - cAMP
SIGMA-ALDRICH