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Molecular and
Cellular Neuroscience
BMP-218
Jeffry R. Alger,
Benjamin M. Ellingson,
and
Allan MacKenzie-Graham
October 29, 2013
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Divisions of the Nervous System
The nervous system is composed of two primary divisions:
1. CNS - Central Nervous System
(Brain + Spinal Cord)
2. PNS - Peripheral Nervous System
(Nerves from CNS to other cells/organs)
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Cells of the Nervous System
The nervous system is composed of two primary types of cells:
1. Neurons
- transmit information
2. Glia
- largely supporting cells
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Neurons
Occur in a wide variety of sizes and shapes, but all share the feature
of cell-to-cell communication
Neuronal Cytoarchitecture
"  Dendrites
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Receives signals from other cells (Input)
"  Cell Body (Soma/Perikaryon)
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Contains cell nucleus
"  Initial Segment/Axon Hillock
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Integrates information
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Fires an action potential (explained later)
"  Axon
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Projects to other cells for communication
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Other neurons, muscles, organs
"  Axon Terminal / Synapses
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Release of neurotransmitters
Myelin
"  Multilayered lipid and protein covering axons at certain areas
"  Electrically insulates axons and increases speed of conduction
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Nodes of Ranvier separate myelinated areas and are important in saltatory
conduction
"  Produced by Oligodendrocytes in the CNS and Schwann Cells in the PNS
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Oligodendrocytes myelinate multiple axons
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Schwann cells myelinate a single axon
Schwann Cell
Oligodendrocyte
Myelin
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Myelin sheath is formed from multiple tight layers
This restricted molecular mobility gives rise to unique characteristics on MRI
Gray and White Matter
"  Gray Matter
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Contains neurons, dendrites, axons without myelin, soma
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Does not contain myelin
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Cerebral Cortex (surface of the brain)
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Deep parts of the brain (nuclei) containing neuron cell bodies
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Central regions of the spinal cord
"  White Matter
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Contains myelin
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Parallel axons surrounded by myelin that traverse from one part of the nervous
system to another
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Peripheral regions of the spinal cord
Myelin stained tissue section of Human Brain
Myelin
(White Matter)
(Stained Dark)
Gray Matter
(No Stain)
Types of Neurons
Classifications of Neurons
"  Afferent Neurons
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Transmits information into the CNS from receptors
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Cell body and long peripheral process of the axon are in the PNS; only the short central process enters the CNS
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Have no dendrites (do not receive inputs from other neurons)
"  Efferent Neurons
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Transmit information out of CNS to effector cells (muscles, glands, other neurons)
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Cell body, dendrites, and a small segment of the axon are in the CNS; most of the axon is in the PNS
CNS
PNS
"  Interneurons
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Function as integrators and signal changers
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Integrate groups of afferent and efferent neurons into reflex circuits
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Entirely in the CNS; 99% of all neurons
Glia
"  Subtypes include:
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Astrocytes
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Oligodendrocytes
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Microglia
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Ependymal Cells
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Choroidal Cells
"  Glia Provide
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Physical (structural) support for surrounding neurons
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Metabolic support for surrounding neurons
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Immune function
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Myelin (Oligodendrocytes in CNS; Schwann Cells in PNS)
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Communication? (Calcium channel communication between astrocytes)
Astrocytes
"  In development, guide neurons as they migrate to their destinations
"  Stimulate neuronal growth by secreting growth factors
"  Forms the Blood-Brain Barrier (BBB), connecting neurons to blood vessels
Astrocytes
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I  n development, guide neurons as they migrate to their destinations
  timulate neuronal growth by secreting growth factors
S
 Forms the Blood-Brain Barrier (BBB), connecting neurons to blood vessels
 Most common type of primary brain tumor (astrocytoma)
Hayden EC, Nature. 2010; 463(7278):154-6.
Oligodendrocytes
"  Forms the myelin covering of CNS axons
Microglia
"  The main phagocytic cell and antigen-presenting cells in the CNS
"  Smallest cell bodies among the neuroglia
"  Immune response / injury
Ependymal and Choroidal Cells
"  Considered glial like
"  Ependymal Cells
cells
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Line the ventricular system in CNS
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Regulate the production and flow of cerebrospinal fluid (CSF)
"  Choroidal Cells
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Form the inner layer of the choroid plexus which abuts the ventricular system in
specific locations
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Secretes CSF into the ventricles
Neurophysiology
Neurophysiology
"  Signaling within groups of neurons depends on three (3) basic properties of these cells:
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The resting membrane potential (most cells)
•  Negative charge on the inside of the cell
•  Positive charge on the outside of the cell
•  RMP ranges from -30mV to -90mV (typically -70mV)
•  [Na+] high on the outside and [K+] high on the inside
2.  Transmembrane protein ion channels (in neurons)
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Transmission of signal along surface of the cell
Controlled (gated permeability) to both K+ and Na+
Projections to other neurons and synapses
•  Between cell signal propagation via a chemical intermediate
(Gated) Ion Channels
Na +/K + ATPase
Na+/K+ ATPase
Uses energy stored in ATP (which is formed mostly by mitochondial
oxidative glucose metabolism) to maintain transmembrane gradients of K+
and Na+
Transports 3 Na+ out while bringing in 2 K+
(Gated) Ion Channels
Na +/K + ATPase
Gated Ion Channels
Allow Na+ and K+ to flow down their concentration gradients
Formation of transmembrane electric current
(Partial) collapse of RMP when gates are open
Gates are controlled by transmembrane voltage (transistor-like properties)
The Action Potential
(electrical transmission of signals
along the neuron)
Action Potential
•  The action potential is a wave of transient depolarization that
travels along the neuron and particularly the axon
•  Depolarization causes voltage sensitive ion channels to open to
propagate depolarization
–  Na+ flows inward (sodium current)
–  K+ flows outward (potassium current)
•  Myelin and Nodes of Ranvier speed the conduction
•  Pharmacology of voltage sensitive channels
–  Site of action of neurotoxic drugs (snake venom, scorpion
toxins, plant alkaloids etc)
–  Site of action of local anesthetics (lidocaine)
Action Potential
depolarization
repolarization
hyperpolarization
Depolarization: Na+ and K + channels open
Repolarization: Na + channels close and K + open
Hyperpolarization: K + channels still open
• HodgkinHuxley model
– Developed in
1950 s through
voltage
recordings with
intracellular
and
extracellular
electrodes in
squid giant
axons
Conduction
A
B
A.  Conduction in an unmyelinated fiber.
Na+ flows in depolarizing adjacent sections of membrane.
Self propagating
B. Saltatory conduction in myelinated fibers.
Myelin insulates and blocks current across membrane
Depolarization occurs at Nodes of Ranvier
Current jumps from node to node
Faster and more energy efficient
Presynaptic neuron
Postsynaptic
neuron
Intracellular Communication: Synaptic Function &
Neurotransmission
•  Signal conveyed by neurotransmitter diffusion across synaptic
cleft
–  Presynaptic electrical signal converted to a chemical signal that is
reconverted to an electrical signal in the postsynaptic cell
–  Slow compared to action potential propagation
•  Specific networks of nerve cells tend to use specific
neurotransmitters
–  Anatomically based networks use specific neurotransmitters
–  Inhibitory neurons frequently use dopamine and GABA
–  Excitatory neurons frequently use glutamate and acetylcholine
Synaptic transmission
Presynaptic events:
- depolarization opens Na+
and Ca2 + channels.
- influx of Ca2 + causes docking
and exocytotsis of
neurotransmitter (NT)
vesicles into the synaptic cleft
Postsynaptic events:
- NT binds to receptors and
opens ion channels that
depolarize the membrane
(excitatory postsynaptic
potential (EPSP)) or
hyperpolarize the
postsynaptic membrane
(inhibitory postsynaptic
membrane (IPSP).
Glial cells remove neurotransmitter from the synaptic cleft
A single impulse doesn t initiate an impulse/action
potential in the post-synaptic neuron
- partially depolarize neuron and bring it closer
to threshold or
- hyperpolarize the postsynaptic neuron and
make it harder to depolarize
Neurotransmitters
Drugs can influence neurotransmitter action
–  Agonists – accentuate neurotransmission
–  Antagonists – suppress neurotransmission
–  Neurotransmitter analogs are used as nuclear
medicine tracers (i.e. 2-deoxy-glucose)
Drugs affecting neurotransmission
Drug effects on action potential
Nicotine and cancer
(www.wikipedia.com)