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The Cytology
of Neurons
Cells of nervous tissue
Neurons and supporting cells
Neurons
Functional units of the nervous system
- transmit sensory (afferent) stimuli from the internal and external
environments
- process, store and integrate information
- transmit to other neurons or muscles and glands (efferent)
Form complex and highly integrated circuits
Heterogeneously shaped, highly active secretory cells
Composed of a cell body, dendrites (somatodendritic domain),
axon and synapses
Neuronal Domains
Somatodendritic
Synaptic
Axonal
Axonal
Somatodendritic
Synaptic
Astrocyte
Supportive cells
Highly outnumber neurons
CNS:
Astrocytes
Structural support
Metabolic support
Homeostasis
Oligodendrocyte
Oligodendrocytes
Insulation (myelin sheath)
Microglia
Phagocytosis
Immunomodulation
Ependymal cells
PNS:
Schwann cells
Microglia
Myelin
Types of Neurons
Shape and modality
Pseudounipolar – sensory (afferent); almost exclusively PNS
Bipolar – sensory; mostly in PNS and retina
Multipolar – motor (efferent) and interneurons; CNS and PNS;
nearly all cells in the CNS are multipolar
Multipolar neurons in the CNS
Spinal motor neuron
(Anterior horn cell)
1. Length of axonal projections
Long distance
Short distance
2. Transmitter type
Excitatory
Inhibitory
Neuromodulatory
Cortical interneuron
Multipolar neurons in the CNS
Inhibitory, local:
Axon terminates locally
Inhibitory neurotransmitters, e.g., GABA,
Interneurons (cortex)
Inhibitory, projection:
Axon terminates at a distance
Inhibitory neurotransmitters, e.g., GABA
Purkinje neurons (cerebellum)
Multipolar neurons in the CNS
Excitatory, local:
Axon terminates locally
Excitatory neurotransmitters, e.g., glutamate
Spiny stellate interneurons (cortex)
Excitatory, projection:
Axon terminates at a distance
Excitatory neurotransmitters, e.g., glutamate
Pyramidal neurons (cortex)
Neuromodulatory:
Axon termination can be local or projection;
Neurotransmitters (NE, ACh, DA) have diffuse,
modulatory role at other synapses.
Structures of neurons
Cell body
Nucleus
Nucleus
Nucleolus
Nissl
Nissl
RER
RER + polysomes
Present in cell body
and dendrites
Polysomes
Golgi
Golgi
Present mostly in
the cell body;
some dendrites
Dendrites
Organelles composition
similar to the cell body
Nissl
Golgi
Axon
Lacks Nissl
Axon hillock
Initial segment
Axon
hillock
Initial
segment
Axon
Myelinated
Unmyelinated
Parallel fibers (cerebellum)
Olfactory axons
The neuropil
Glial cell
nuclei
The neuronal cytoskeleton
Neuronal
cytoskeleton
Microfilaments (4-6 nm)
Neurofilaments (8-10 nm)
Microtubules (20-25 nm)
Dendrite (xs)
Neurofilaments
SER
- Gives shape and support to the
40,000x
neuron
- Facilitates intracellular transport
Axon (ls)
- 25%-35% of total cell protein
- Neuronal pathologies often involve
the cytoskeleton either directly
or indirectly
Microfilaments
Microtubules
MF
MT
NF
12,000x
Microfilaments
Similar to microfilaments found in all cells, with neuron specific isoforms
of the actin protein.
Concentrated beneath the plasma membrane where they provide support
for the plasma membrane and anchorage for membrane proteins.
Prominent at nodes of Ranvier, post-synaptic densities.
Form the core of dendritic spines.
Node of
Ranvier
Sub-membrane distribution
Dendritic spine
Neurofilaments
Neurofilaments are intermediate filaments specific to neurons
Provide support and stabilization; stable slow metabolic turnover.
Phosphorylation gives additional stability in axons, especially in large,
myelinated axons
-PO4
-PO4
-PO4
-PO4
-PO4
50,000x
Microtubules
Similar to microtubules found in all cells, with neuron specific isoforms of
tubulin proteins
Provide the “intracellular highway” for transport
NF
MT
Longitudinal section
Cross section
Intracellular transport
Major synthetic site is the cell body
Molecules and pre-formed organelles must be transported distally
Return of materials for recycling
Occurs in dendrites and axons, first studied in axons (axonal transport)
Fast transport (200-400 mm day)
Anterograde = away from the cell body
Neurotransmitter vesicles
Vesicles for membrane insertion
Mitochondria
Retrograde = toward the cell body
Recycled organelles
Endocytic vesicles
Direction of transport depends on the orientation of the
microtubules and different cargo motors.
Mechanism of fast transport
Organelles (cargo) are transported along the “microtubule highway” by
molecular motors which are ATPases:
Kinesin - Anterograde transport, toward (+) end
Dynein – Retrograde transport, toward (-) end
Organelles bind to their specific motor move along the microtubule in a
direction dictated by their motor.
Altered axonal transport in neurodegenerative diseases
Primary:
Charcot-Marie-Tooth disease type 2
Peripheral neuropathy with axonal degeneration.
Distal motor weakness, loss of touch sensation, wasting.
Develops in late childhood/early adulthood.
Mutation in the kinesin isoform transporting mitochondria.
One of the most common
inherited neurological disorders
(37/100,000)
Secondary: Neurodegenerative disease (Huntington’s, ALS, Alzheimer’s and
Parkinson’s); may result from abnormal intraneuronal inclusions.
Synapses
Presynaptic
terminals
The chemical synapse
Specialized adhesive contacts
Site of neurotransmitter release by
vesicle exocytosis (bouton)
Transmitters diffuse across a gap
which physically separates the cells.
(synaptic cleft)
Transmitters bind to receptors on the
post-synaptic structure producing
alterations in the state of membrane
polarization (post-synaptic density).
Structurally asymmetric, unidirectional
transmission.
Pre-synaptic terminal (bouton)
Neurotransmitter vesicles
Mitochondria
Actin (support and vesicle movement)
Tubulo-vesicular membranes
Active zone
Mito
Active zone
Transmitter vesicles
Clear vesicles (30-50 nm)
Dense core vesicles
Clear vesicles – ACh, GABA, glutamate
Dense core vesicles - catecholamines
(epinephrine/norepinephrine)
Large dense core vesicles – neuropeptides
(substance P, somatostatin)
Some terminals can contain more than
one type
Large dense core vesicles 70-200 nm
Active zone
Pre-synaptic
Synaptic cleft
Active zone
Post-synaptic
Pre-synaptic
25 nm
Postsynaptic density
Postsynaptic
density
Synaptic
cleft
Dendrite spines
Small elevations (2 microns) on the surface of some dendrites.
Receive the majority of excitatory input to the neuron.
20,000 spines/pyramidal neuron.
40% of the total surface area of some neurons.
Inhibitory synapses occur more on proximal dendrites (shafts) and soma.
Spine apparatus
Extension of the SER in the dendritic spine.
Associated with actin filaments and ribosomes.
Function is unclear, may be the site of synaptic protein synthesis and
calcium homeostasis, both important in synaptic plasticity.
SER
Functional significance of dendritic spines
Highly labile structures, form or collapse in seconds.
Enriched environments increase the number of dendritic spines.
Normal
Sensory Deprived
Spine morphology and function are altered in mental retardation and Fragile-X
syndrome.
Excitatory vs inhibitory synapses
Excitatory synapses (Gray type I)
Spherical vesicles (e.g., acetylcholine, glutamate)
Asymmetric – Conspicuous postsynaptic density
Wide synaptic cleft
Inhibitory synapses (Gray type II)
Oval vesicles (e.g., GABA)
Symmetric – Less conspicuous postsynaptic density
Narrower synaptic cleft
Excitatory
Inhibitory
Excitatory
Excitatory
Inhibitory
Inhibitory
Classification of synapses based on postsynaptic structure
Axo-dendritic and axo-spinous (most numerous)
Axo-somatic
Axo-axonic (on presynaptic terminals)
Synaptic vesicle synthesis
and trafficking
1.
Delivery of synaptic vesicle components to
plasma membrane
2.
Endocytosis of vesicle components to form
new synaptic vesicles directly
(major pathway)
3.
Endocytosis of synaptic vesicle components
and deliver to tubulo-vesicular membranes
(minor pathway)
4.
Budding of synaptic vesicle
5.
Loading of neurotransmitter into synaptic
vesicle
6.
Secretion of neurotransmitter by exocytosis in
response an action potential and calcium
Synaptic vesicle synthesis and trafficking
Large dense core vesicles
Vesicles and their contents are synthesized in the
cell body
Transported by fast axonal transport
Synaptic and extra synaptic release (cell body
and dendrites)
Secreted by a regulated mechanism similar to
peptide hormones; merocrine release
Release in response to burst firing and
increased intracellular calcium
Release slower and more sustained than synaptic
vesicles; no recycling
Chemical vs
electrical
synapses
Chemical
Slower, neurons are separating by a space
Maximal plasticity
Use chemical transmitters, sensitive to drugs and toxins
Unidirectional (asymmetric)
Most common
Electrical
Fast, provide ionic coupling via gap junctions
Minimal plasticity
Restricted distribution found in selected brain regions and
throughout the retina
Electrical synapses (coupling)
The Tri-partite synapse
Astrocytes surround synapses in the CNS
Scavenger function of ions and transmitter
Each astrocyte contacts over 140,000 synapses
Glutamate uptake and release
Halassa, et al., Trends Mol. Med., (2007)