Transcript Review of the Nervous System MAJOR FUNCTION: COMMUNICATION Organization of the Nervous System.

Review of the
Nervous System
MAJOR FUNCTION:
COMMUNICATION
Organization of the Nervous System
Neuron Anatomy
Neuron Gross Anatomy
• Neurons are structurally different from other
cells in the body.
• Their unique structure belies their function.
- Axon
- Dentrites
- Synapses
Neuron Cell Body
•
Has pretty much the same organelles
(ribosomes, RER, SER, Golgi apparatus,
lysosomes, secretory vesicles, etc.) as those
of other cells, with some minor differences:
1. Mitochondria present in processes, as well as
the cell body itself, because of the energy
requirements of maintaining the
transmembrane ion potential (resting
membrane potential); thus, usually more of
them than in your average somatic cell.
Neuron Structure
Neuron Cell Body (cont’d)
2. Cytoskeleton – perhaps the most obvious structural
difference between neurons and other cells,
obviously because of the formers’ asymmetrical
nature.
a. Microfilaments [actin (growth cones) and myosin
(growth cones, skeletal mus)].
b. Neurofilaments (intermediate in size between
microfilaments and microtubules; implicated in
tangles in AD).
c. Microtubules – part of the cytoskeleton, act in
axonal transport of vesicles, and act as molecular
motors to move organelles (e.g., mitochondria)
along.
Axonal Transport of Membranous Organelles by
Microtubules
Motor Proteins
• Kinesin – carries organelles in the (+)-end
direction.
• Dynein – carries organelles in the (-)-end
direction.
• See Figs. 1.10 and 1.11.
Cytoskeleton Motor Proteins
Kinesin and Dynein
Myosin: A 3rd Motor Protein
The headgroup of mysosin walks toward the
head group of the actin filament (microfilament)
Your Typical Presynaptic and
Postsynaptic Neurons
Axon
• Thin, tube-like process that emanates from the
cell body at a cone-shaped thickening, called
the ‘axon hillock’.
• Length can range from microns to meters.
• Diameter remains relatively constant over its
length.
• Shape is maintained by the cytoskeleton.
• Carries nerve impulses (information) to the
soma
Dendrite(s)
• Neuronal processes that tend to be thicker and
much shorter than axons.
• Highly branched  dendritic tree or arborization.
• Unlike axon, dendrites can occur just about
anywhere on the neuron.
• Can grow small finger-like projections from the
main dendritic shaft, called spines.
• These spines are the synaptic input sites where the
neuron receives information from other cells.
• However, some dendrites also transmit electrical
signals.
Dendrites (cont’d)
• Dendritic structure is not fixed and immutable.
- Under certain physiological conditions, such
as learning, stress, growth, disease, or aging (to
name just a few), the size and shape of dendritic
spines can dramatically change on a rapid time
scale (a few minutes).
• Carries nerve impulses (information) away from
the soma.
- These are the so-called plastic changes –
more later in the quarter.
Neuronal Polarity
Dendrites
Axons
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Uniform calibre
Few branches
Lack polysomes
Little, if any, protein synthesis
Fast growth
Neurofilament abundant
Uniform polarity of
microtubles
Narrow spacing between
microtubules
Abundance of tau protein
Presence of αγ spectrin
Highly phosphorylated NF-M
and NF-H
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Tapered morphology
Highly branched
Presence of polysomes
Some protein synthesis
Slow growth
Abundance of microtubles
Mixed polarity of microtubules
Wide spacing between
microtubules
• Presence of MAP2A, B
• Presence of αβ spectrin
• Nonphosphorylated NF-M and
NF-H
Classification of Neurons
Sensory Neurons
• afferent
• carry impulse to CNS
• most are unipolar
• some are bipolar
Interneurons
• link neurons
• multipolar
• in CNS
Motor Neurons
• multipolar
• carry impulses away
from CNS
• carry impulses to
effectors
Synapse (= Connect) (Greek)
• First discovered by Charles Sherrington near
the end of the 19th century.
• Studied reflexes, which do not require the
brain at all.
• Form the basis of intercellular communication.
• But synapses, like dendrites, are not fixed.
- Rather, there is a thing, called synaptic
strength or strength of synaptic transmission.
Synapses
Nerve impulses pass
from neuron to
neuron at synapses
Synaptic Transmission
Neurotransmitters are
released when impulse
reaches synaptic knob
Synapses (cont’d)
• Synaptic strength can be modified according to
the physiological state of the animal.
- Is the animal learning?
- Is the animal suffering from some disease?
(Does not necessarily have to be a
neurally-oriented disease).
- Is the animal thriving or deprived?
- Is the animal aging?
- Has the animal been taking drugs (abuse or
therapeutic)?
Synapses (cont’d)
Two Kinds of Synapses
1. Chemical
2. Electrical
• Both types of synapses relay information, but do
so by very different mechanisms.
• Much more is known about chemical than about
electrical synapses.
- Information gleaned from NMJ in frog leg
(sciatic n. – gastrocnemius m.).
- However, this is n-m, rather than n-n.
- n-m relay is much faster than n-n.
Axon-dendrite
Axo-axonic
Axon-soma
Chemical Synapses
• Asymmetric morphology with distinct features
found in the pre- and postsynaptic parts.
• Synaptic cleft is ~ 200-300 angstroms wide.
• CHO moities intersperse the synapse.
• Most presynaptic endings are axon terminals.
• Most postsynaptic elements in the CNS are
dendrites.
• There are all the combinations of synapses:
axosomatic, axodendritic, axoaxonic.
Chemical Synapses (cont’d)
• Convergence.
• Divergence.
• Presynaptic ending:
- swelling of the axon terminal.
- mitochondria.
- a variety of vesicular structures,
clustered at/near the very edge of the
axon terminal.
Convergence
• neuron receives input from
several neurons
• incoming impulses represent
information from different
types of sensory receptors
• allows nervous system to
collect, process, and respond
to information
• makes it possible for a
neuron to sum impulses from
different sources
Divergence
• one neuron sends
impulses to several
neurons
• can amplify an
impulse
• impulse from a
single neuron in
CNS may be
amplified to
activate enough
motor units
needed for muscle
contraction
Chemical Synapses (cont’d)
• Postsynaptic element
- comprised largely of an electron-dense
structure, called the postsynaptic
density (PSD).
Function of PSD?
- Anchor receptors for nts in
the postsynaptic
membrane.
- Involved in the conversion of
chemical signal into an
electrical one =
transduction.
Chemical Synapses (cont’d)
• Associated with the morphological asymmetry is that
chemical synapses are, for the most part, unidirectional.
• There is a delay of a msec or more between the arrival
of information at the presynaptic terminal and its
transfer to the postsynaptic cell.
This delay may reflect the several steps
required for the release and action of the
chemical neurotransmitter.
The response of the postsynaptic neuron may
be sustained (long-lasting), much longer
than the presynaptic signal the evoked it.
This may reflect long-lasting changes in the target
(receiving) cell.
• More on Chemical Synapses later in the course.
Electrical Synapses
• Symmetrical morphology.
• Bidirectional transfer of information.
• Pre- and postsynaptic cell membranes are in close
apposition to each other, separated only by gap
junctions.
- Ions can flow through these gap junctions,
providing low-resistance pathway for
ion flow between cells without leakage
to the extracellular space.
- Instantaneous, fast transfer from 1 cell to
the next, unlike the delay seen with
chemical synapses.
Electrical Synapses (cont’)
Putative Functions
• Synchronization of the electrical activity of large
populations of neurons;
- e.g., the large populations of neurosecretory
neurons that synthesize and release biologically
active peptide neurotransmitters and hormones are
extensively connected by electrical synapses.
- e.g., Synchronization may be required for neuronal
development, including the development of chemical
synapses.
- e.g., Synchronization may be important in functions
that require instantaneous responses, such as reflexes.
• More on Electrical Synapses later in the course.
Neuroglia Anatomy
Types of Neuroglial Cells
Types of Neuroglia Cells
Schwann Cells
• PNS
• myelinating cell
Oligodendrocytes
• CNS
• myelinating cell
Microglia
• CNS
• phagocytic cell
• respond to injury,
infection or disease
Astrocytes
• CNS
• scar tissue (“nerve glue”)
• clean up
• mop up excess ions (K+),
nts, etc.
• induce synapse formation
• connect neurons to blood
vessels
Ependyma
• CNS
• ciliated
• line central canal of spinal cord
• line ventricles of brain
Glial Functions
• Provide myelin [Oligodendrocytes (CNS); Schwann cells
(PNS)]
• Act as scaffolding for neuronal migration and axon outgrowth.
• Participate in the uptake and metabolism of the
neurotransmitters that neurons use for intercellular
communication.
• Take up and buffer ions from the extracellular environments.
• Act as scavengers to remove debris produced by dying
neurons.
• Segregate groups of neurons from each other and act as
electrical insulators between neurons.
• Provide structural support for neurons (c.f., role fulfilled by
connective tissue cells in other organs).
• Nurturant role: Supply metabolic components and even certain
proteins necessary for neuronal function.
• Participate in intercellular signaling; perhaps playing a role in
information handling and memory storage.
Glial Cell Functions
Myelination of Axons
• As per the previous slide,
certainly not the only
function, but arguably the
most important function,
whose malfunction is the
basis for several wellknown, highly debilitating
diseases.
White Matter
• contains myelinated
axons
Gray Matter
• contains
unmyelinated
structures
• cell bodies, dendrites
OLIGODENDROCYTES (CNS) & SCHWANN CELLS (PNS)
Processes of both types wrap around axon(s), forming an insulating sheath called myelin.
Oligodendrocyte: its processes form multiple internodes on different axons and its cell body
is located between the different axons.
Schwann cell: its process forms only one internode, and its cell body is located on the axon.
Astrocytes buffer the Environment
Against an Accumulation of K+
• Astrocytes take up K+ ions from the extra-cellular
space.
• This occurs through K+ channels located on
astrocyte cell bodies.
• K+ is then released back into the extracellular
space through their endfeet in areas that are
relatively low in [K+] (running down the conc
gradient).
• Particularly important at the Nodes of Ranvier.
• Why might such K+ buffering be important
anyway?
•Astrocytes take up
K+ ions from the
extracellular space.
•K+ is released
back into the
extracellular space
through their
endfeet in areas
that are relatively
low in [K+]
(running down the
concentration
gradient).
Astrocytes Regulate Neuronal
Cytosolic [Ca2+]s
• Astrocytes release chemicals called
“gliotransmitters”, glutamate, ATP, D-serine, and
TNFα.
• This suggests that astrocytes are excitable cells.
• Yet, their excitability is not based on Vm as it is in
neurons, but rather, on changes in [Ca2+]i.
• Astrocytes, connected together by gap junctions,
have been shown to signal each other (and
neurons) via intercellular Ca2+ pulses.
Astrocytes Regulate Neuronal
Cytosolic [Ca2+]s (cont’d)
• The activity-driven response in astrocytes is
extremely sensitive to the level of neuronal
activity:
e.g., A 1% increase in [isofluorane] causes a 16%
decrease in neuronal response to visual
stimulation, but a 77% decrease in the astrocytic
response to the same visual stimulus.
This suggests that astrocytes’ role may be in finetuning the stimulation-induced responses (e.g.,
orientation and spatial frequency) of neurons.
Astrocytes Regulate Neuronal
Cytosolic [Ca2+]s (cont’d)
• Such studies have shown that stimulation in
rodents (e.g., whisker, limb, odor) releases
Ca2+ from astrocytes.
• Astrocytic Ca2+ release is largely mediated by
the activation of metabotropic glu receptors
(mGluRs).
• Stimulation of mGluRs modulates arteriole
diameter (bp) and are dependent on Ca2+
signaling, involving multiple glial cells.
Astrocytes are Neuroprotective
• Secrete neurotrophins.
• Main defense against brain glutamate
excitotoxicity.
• K+ buffering.
• Astrocytes express high amounts of connexins,
the main protein of gap junctions.
Through these gap junctions, glucose and
metabolites are allowed to pass, thereby
strengthening the astrocytic network, which, in
turn, strengthens the neuronal network.
Bidirectional Communication between
Neurons and Astrocytes
(b) Hippocampal activity is increased, but is scaled back and fine-tuned by astrocytereleased TNFα
Astrocytes Participate in the
Neurotransmitter Cycle
• Astrocytes help take up neurotransmiters in the
synaptic cleft so that they do not continuously
bind their receptors on the postsynaptic cell.
• This supplements the uptake mechanisms and
degradation mechanisms that neurons already
have in place.
• Such supplementation may be particularly
important for high [neurotransmitters]s (e.g.,
glutamate, whether naturally or drug-induced).
Life cycle of a neurotransmitter
An excitatory (glutamatergic)
synapse
A synapse using g-aminobutyric acid (GABA)
A synapse that uses acetylcholine (ACh)
Astrocytes Modify Synaptic Function
in Time and Space
SPACE
• Astrocytes release gliotransmitters not only at
processes of the astrocyte contacting the synapse:
- Transmitter release may occur close to the
synapse.
- Transmitter release may occur into the synapse.
e.g., release of D-ser modifies synaptic NMDA
receptors.
Astrocytes Modify Synaptic Function
in Time and Space (cont’d)
TIME
• Both neuronal and astrocytic input determine the
outcome of synaptic plasticity.
• Timing is critical for determining extent of synaptic
plasticity.
e.g., Astrocytes release ATP both tonically and in an
activity-dependent manner:
Constant release of ATP that is rapidly degraded to
adenosine provides a tonic suppression at hippocampal
synapses. [recall tonic Ca2+ release for cell-cell
communication].
But activity-mediated ATP release from astrocytes is
responsible for heterosynaptic depression.
Astrocytes can provide Neurons with
ATP both Directly and Indirectly
Directly
• Some of the adenosine released by astrocytes are
taken up by neurons to be used to manufacture
ATP.
• Astrocytes can provide neurons with glucose.
Indirectly
• Astrocytes numerous radiating processes that
cover neurons and nearby capillaries support and
brace the neurons and anchor them to their
nutrient supply lines (capillaries).
Astrocyte
Astrocytes Help Form the Blood Brain Barrier
• Basal lamina of the astrocytes
+ the astrocytic endfeet
produce help maintain the
BBB.
• Notice how astrocytes send
processes to the external
surface of the CNS where the
endfeet form the glia limitans
externa, which separate the pia
mater from the nervous tissue.
• Gap junctions and desmosomes
join the endfeet to form a space
between neurons and vascular
endothelial cells (Fig. 2.2).
Ependymal Cells
• Line the walls of the ventricles of the brain and
central canal of the spinal cord.
• Produce CSF.
• Have cilia on their apical ends, which beat and
help distribute the CSF that help cushion the
brain and spinal cord (refer to preceding slide).
Microglia
• Branches touch nearby neurons to monitor the
latters’ health.
• If there is neuronal ill-health or injury, microglia
mobilize and migrate towards them.
• If invading microorganisms or dead neurons are
present, microglia transform into a microphage,
which then phagocytises the debris.
• Critically important, given that the immune
system cells have no access to the CNS.
Microglia