20110105 02 nervous notes.txt

From Iusmhistology

  • started here on 01/05/2011 at 2PM.


Contents

[edit] Lecture Objectives-Nervous System

  1. Describe the basic organization of the nervous system and the main structural features that distinguish the central nervous system from the peripheral nervous system.
  2. Define the unique cell types that make up nerve tissue and the structural specializations that distinguish neurons from glial and other supporting cell types.
  3. Understand the role of axonal transport in maintaining the structure and function of neuronal processes and synaptic terminals.
  4. Compare the structural and functional features of myelinated and unmyelinated axons and describe the basic events in axon myelination.
  5. Describe the structure and function of the synapse.
  6. Understand the structure of the spinal cord and the histological detail that distinguish the gray matter from the white matter.
  7. Compare and contrast the structure and organization of the somatic motor and visceral motor system.
  8. Define the structural features and functions of glial cell types.
  9. Understand structure/function correlates associated with nervous system pathologies including Alzheimer's disease, cerebral ischemia, multiple sclerosis and referred pain.

[edit] NERVOUS SYSTEM

  • Clinical relevance:
    • 11K injuries per year
    • Stroke is third leading cuase of death and #1 cause of disability
    • Parkinson's disease: 40K cases / year
      • Neuronal degeneration
    • Alzheimer's disease: 4.5 million cases, 100$ billion per year
      • Brain volume decreases.

[edit] Basic organization

  • Central nervous system (CNS)
    • Brain:
      • Gray matter and nuclei (surrounds the white area; there are also "nuclei" of grey mater in the center of the brain.
      • white matter (nerve fiber tracts)
    • Spinal cord:
  • Peripheral nervous system:
    • Ganglia: clusters of neuronal cell bodies.
    • Nerve fibers:
      • Efferent---motor, from CNS to peripheral
      • Afferent: from peripheral to central, sensory
  • Neurons and glial cells
    • There are many more glial cells than neruons.

[edit] Neurons

  • Neurons can be classified:
    • Number of primary processes: multipolar (many processes), bipolar (two), pseudounipolar (rarely found in ...)
    • Function: excitatory, inhibitory, modularatory
    • By transmitter: gluatmic acid, GABAergic, dopamine, etc.
    • Other: projection neurons, interneurons, pyramindianl neurons (shape), granule cells, etc.
  • Examples
    • multipolar, GABAergic, inhibitory, and has many spines (multi-spinous).
    • ?
    • ?
    • Fake neuron, a large aspinous neuron, non-projection neuron (previous three are projection neurons)

[edit] Cell body

  • AKA perikaryon, soma
  • The nucleuous has a prominent nucleolus 
Why?
  • Have much rER, generates dots called Nissl bodies.
  • Has golgi, MT (microtubules), and mts (mitochondria), IFs (called neurofilaments), lyposomes (lipofuscins).
  • Mt look like cucumbers in shape.

[edit] Dendrites

  • One of the two major types of processes: axons and dendrites.
  • Dendrites receive inputs from all surrounding cells.
  • There are primary dendrites that branch into small and smaller dendrites.
  • There are samll dendrtitic spines
  • There are apical and basalar dendrites.
  • How do we determine apical versus basal?
    • Apical will face away from the cortex of the brain (toward the exterior).
  • There is a head and neck to the spines.
  • What do the spines do?
    • They seem to allow synapsing with neuron neighbors.

[edit] Axon

  • Send info to ther neurons ("upward").
  • Axons are much longer than dendrites.
  • There is only one axon per nerve cell, though they can branch extensively.
  • There is an axon hillock which is begun by the initial segment. Then there are collaterals given off and terminations in the "terminal".
  • There are many MTs ant mts in the axon hilock.
  • Axonal transprot moves material from the soma to the terminal and vice versa.
    • There are fast and slow transport of vesicles along the axon.
    • Fast is several hundred mm / day
    • Slow transport is a few mm / day, moves soluble components and cytoskeletal structures.
  • There are two directions, too:
    • Anterograde: from body to peripheral via kinesin
    • Retrograde: from peripheral to body via dynein

[edit] Synapse

  • The site of communication between two neurons.
  • Two types of synapse:
    • Electrical synapse
      • Fxn through gap jxns
      • Allows passage of ions form cell to cell.
      • Few of these in mammals
      • Very fast
    • Chemical synapse
      • Three components: presynaptic, synaptic cleft, postsynaptic.
      • The postsynaptic component can be just about any part of the post-synaptic cell (dendrite, soma, axon, spine).
      • Note that in chemical synapses, the signals must be converted from electrical in the presyn cell to chemical and back to electrical in the postsynap.
  • How do synapses work?
    • It's about the resting memebrane potential, the synaptic potential, and the action potential.
  • Spines are not fixed; they are always changing in length, location, number of branches, etc.

[edit] Glial cells

  • Oligodendrocytes in the CNS and Schwann cells in the PNS.
  • Produce myeling sheath to cover axons.
  • Myelin is a lipoportein complex, an insulation; keeps ions from flowing freely around the axon.
    • With no myelin, bad transduction.
  • In the CNS: a single oligodendrocyte generates the insulated area between nodes of ranvier.
  • On an EM, the myelination shows as black area along the axon.
  • Myelination and nodes of ranvier provide AP leaping which is faster.
  • Unmyelinated firbers:
    • In PNS, one schwann cell envelops many axons.
    • No sheathes in CNS
    • These have slow conductance. 
Are all CNS / PNS myelinated / non myelinated?

[edit] Spinal cord injury

  • Myelin is important for guiding regenerating axons.
  • Bridging is an attempt to make regeneration work: put in a tube filled with schwann cells to help guide the regenerating axons passed the injury.
    • It has been shown that axons may actually grow through the tube and help therapeutically.

[edit] Astrocytes

  • Most numerous glial cells in CNS
  • Two types
    • Fibrous:
      • Long, thin processes
    • Protoplasmic astrocytes:
      • Found in grey matter
      • Short and fat processes
  • Have end feet: connect to epithelium and sit on the external surface of the CNS
  • Provide physical support for neurons
  • Maintain homeostasis (toxin processing, extra NT processing, etc)
  • Release neurotrophic factors (regulate transuction, still unknown)
  • Can be found between two neurons and may help transduce signals
  • Astrocytes can interact with neurons through the neuron's spine and their own form of a spine.
  • Astrocytes are increased after ischemia of the brain (cns).
    • So in early ischemia, astrocytes may proliferate in order to rescue the neurons.
    • When ischemia is severe enough that neurons don't survive, the astrocytes generate a type of scarring material.

[edit] Blood brain barrier

  • Important fxnal barrier to restrict exchange of substances between brain and blood.
  • Has four components:
    • Endothelial cells
      • Provide an occluded junction which keeps even ions from passing between cells
      • Have low transcytotic activity (that is, low transport into and out of the cytoplasm).
    • There is a basement membrane
    • There are end feet of astrocytes
    • There are pericytes
      • Provide another barrier in the BBB.
  • All four of these form the BBB.

[edit] Microglia

  • These are macrophages in the CNS
  • Come from bone marrow
  • In immune responses, they get turned on (IL4) and phagocytize stuff.
  • They are generally very small compared to neurons and astrocytes.
  • In MS, myelin is degenerated by microglia.
    • In the inital phase: some pathogen enters the brain such that the microglia are activated.
    • Then a second agent comes in and symptoms get worse.
    • This gives the relapsing-remitting time-course of disease.
    • There are abs generated against the myelin at increasing levels at each relapse.
  • There are two forms of MS: RR and multi-organ MS.
    • Many organs get attacked in MS.

[edit] CNS

  • The brain is covered in neuro, we'll talk about spinal cord.
  • There is a central canal which is lined with ependymal cells (celiated cuboidal epithelium).
  • There is also grey matter
    • Forms the dorsal, lateral, and ventral horns as well as the neuropil.
      • Ventral = motor
      • Dorsal = sensory
      • Neuropil is anywhere without cell bodies.
  • There is white matter:
    • Descending and ascending fiber tracts

[edit] PNS

  • Ganglia:
    • Cell body collections
    • Three types:
      • Sensory,
      • Autonomic ganglia
  • Nerve fibers:
    • myelinated and unmyelinated fibers
    • Epineurium, perineurium, and endoneurium
      • This is just like with muscle (endo / peri / epi myseum).
      • A single neuron has myelin around it then the endoneurium.
      • Several neurons will be bundled via perineurium.
      • A whole nerve bundle will be surrounded by the epineurium.

[edit] Somatic nerves

  • Two major types of nerves: somatic and visceral
  • Two types of somatic nerves:
    • Sensory
      • Dorsal root ganglia
      • Very precise as to where the signal came from.
    • Motor
      • from motor neurons to skeletal muscles
      • Use ventral horn
      • Fast
      • Precise

[edit] Visceral nerves

  • Control smooth muscle, glands, cardiac rhythm, and body homeostasis
  • Two tyeps:
    • Sensory
      • From internal organs to CNS
      • Go through DRG
      • Difuse and vague
      • Generate referred pain because conduction is back to the spinal cord, to the dorsal horn at the same place as the somatic sensory nerves. the brain may interpret the pain as somatic when it is actually visceral? 
Can it be interpretted in the opposite way?
    • Motor
      • There is a sympathetic system
        • The thoracolumbar division uses ach and sympathetic ganglia to control heart, glands, and smooth muscle
        • Has short pregangliotic fibers and long post-gangliotic fibers.
        • Functions to increase awareness and survival
      • There is a parasympathetic system:
        • the Craniosacral division uses ach and parasympathetic ganglia to control heart, gland, smooth muscle etc.
        • The preganglionic fibers are relatively long; the postganglionic fibers are relatively short.
        • Function to conserve energy.

[edit] Lab

[edit] PERIPHERAL NERVE

[edit] Slide 9 sciatic nerve dog

  • Osmium tetroxide was used to fix these nerves.
    • This preserves lipids and stains them brown or black.
    • Adiposites in this slide show up as black.
    • Myelin on this slide shows up as brown.
  • The organization of the nerve fibers are seen:
    • All three fibers are collagenous connective tissue.
    • Epineurium is the outer layer:
      • Coursest of the three layers
      • Surrounds an entire nerve bundle
    • Perineurium
      • Surrounds the entire nerve bundle and projects deep into the bundle of axons to merge with the endoneurium.
      • Easiest to identify it at the very outside edge of the axon.
      • Seems a little more wavy and less collagenous than the epineurium.
    • Endoneurium is the inner layer:
      • Most delicate
      • Immediately surrounds the myelinated axons.
  • Myelin can be identified around each axon by it's brownish color that is circular in a cross-section and wide-spread in longitudinal cut.
    • The myelin will surround the delicate endoneurium which is stained pink.
    • Around the dark band of myelin, there is a small gap and then another, thinner dark band representing the outside edge of the schwann cells.
      • This gap is larger than in real life as there is shrinkage of the myelin away from the schwann cell body.
  • There is also shrinkage between the myelin and the cytoplasm of the axon which in this slide appears pink.

[edit] Slide 15 Peripheral nerve

  • This slide is stained with Masson's trichrome
    • Connective tissue will be a blue-green
    • Nuclei will be a purple.
    • Myelin is blotch white
  • The schwann cell is wrapped around the axon so its nuclei stain is purple and arched around the axon like one expects the myelin to be.
  • The nuclei of the distributed fibroblasts are slight better defined (sharper edges), are elongated, not arched, and are found in the midst of connective tissue (blue-green) as opposed to the blotchy whiteness of myelin.
  • Unmyelinated axons can be seen on slide 15 and 9.
  • These axons are tucked into invaginations of the cell membrane of schwann cells.
    • These invaginations form channels for each axon.
    • These will generally occur at very small axons.
    • Recall that unmyelinated neurons will occur in the peripheral nervous system.
    • These neurons will be to parasympathetic things like smooth muscle control because we don't need things to happen quickly.
  • One cannot be sure that a neuron doesn't have myelin simply by light microscope so we are not responsible for determining if a neuron has myelin or not.

[edit] Nodes of Ranvier

  • Nodes of Ranvier are generated by the end of one myelin covering and the beginning of another meet.
  • The nodes can be identified in slide nine by the pinching of the pink endoneurium at a sharp point
    • These nodes are very small in distance so with light microscope it is not possible to see the separation of the two myelin sheaths.
  • Perpendicular to the pinched area will be a shriveled axon, much thinner than the distance between the layers of the endometrium on the sides of the axon.

[edit] =Slides 10, 82, and 25

  • "Other Examples of Peripheral Nerve: Several slides in the collection contain peripheral nerves. The nerves in slide 10 (mesentery) are easy to find. These are unmyelinated nerves. If you have time, take a look at slide 82 (spermatic cord) where most of the nerves are unmyelinated, and slide 25 (lymph node), which also contains unmyelinated fibers." 
Need help finding neurons on slide 82.

[edit] SPINAL CORD AND GANGLIA

  • Peripheral nerve fibers can contain somatic motor, visceral motor, and sensory neurons.
  • The cell bodies of each neuron type is located in a specific area (either the spinal cord of the CNS or ganglia of the PNS):
  • To understand why nervous tissues appear the way they do, it is helpful to understand where neuronal cell bodies reside.
  • Be familiar with the following:
    • Pseudounipolar (somatic or visceral) sensory neurons.
    • Multipolar somatic motor neurons.
    • Multipolar visceral preganglionic motor neurons.
    • Multipolar visceral postganglionic motor neurons.

[edit] Spinal Cord

[edit] Slide 6 Spinal cord, cervical, monkey
  • This slide uses a Nissl stain:
    • Recall that rER in neurons is also called Nissl bodies
    • Causes rER to be a deep blue
  • In the ventral horn, multipolar visceral motor neurons can be identified by their heavy blue / purple staining of rER.
[edit] Slide 17 Spinal cord ganglion, mammal
  • This is an H&E stain:
    • Basophilic structures like the rER will be stained blue because of hematoxylin.
  • One can identify the dorsal horn, the ventral horn, multipolar motor neurons in the ventral horn, and the dorsal root ganglion.
    • Recall that the horns are grey matter, surrounded by white.
  • The dorsal root sends afferent ("at" the CNS) fibers from the dorsal root ganglion to the dorsal horn of the spinal cord grey matter.
  • The ventral root carries efferent ("exit" the CNS) fibers from the spinal cord to to visceral motor effectors.
  • The ventral horn contains cell bodies of somatic motor neurons.
    • These cells have much euchromatin and large nucleoli -- both signs of high metabolism.
  • Multipolar cells will have several processes shooting off.
    • There is however, only one axon.
    • The axon may not be the largest process.
    • The axon can be identified by the presence of the axon hillock.
    • The axon hillock will stain lighter than rest of the cell because it has many MTs but little rER and few mt. 
*"Neurons dispersed within tissue that has almost no intercellular space. Nuclei of the surrounding cells are easily visible, but cell boundaries are hard to see. There are many capillaries present, but most of the nuclei in the surrounding tissue belong to glial cells. The material surrounding the cell bodies is composed of processes of neurons and other glial cells, and is called the neuropil (a feature of the CNS)."
  • The white matter has much smaller nuclei and a more homogenous speckled look (probably because the cells are running into and out of the cross-section instead of branching in parallel with the cross-section cut). 
*Is there a name for the cells that bridge the grey and white matter?


  • stopped here on 01/05/11 at 6PM.
  • started here on 01/07/11 at 12:45PM.


  • The lateral horn houses cell bodies of autonomic motor neurons that innervate smooth muscle and glands.
  • Somatic motor neuron axons run through the ventral root and bypass the DRG.
  • Visceral motor neurons have cell bodies in the ventral horn; axons travel through the ventral root, bypass the dorsal root ganglion, follow nerves that lead to peripheral ganglia. 
But they don't synapse in the peripheral ganglia?
They just synapse directly on the motor cells?
    • Note that this is a one-cell communication between the CNS (spinal cord) and the effector cell (skeletal muscle).
  • The autonomic nervous system takes two cells for CNS-to-effector communication.
    • Here there are preganglionic cells and post ganglionic cells with ganglia as their point of synapse.
    • The cell body of the preganglionic cells is in the spinal cord.
    • The cell body of the postganglionic cells is in the respective ganglia.
  • There are two divisions to the autonomic nervous system: parasympathetic and sympathetic.
    • The sympathetic system is characterized by short pre-ganglionic axons that synapse in ganglia that is very near to the spinal cord (think "sympathetic chain ganglion", etc.).
      • Subsequently, the post-ganglionic fibers are much longer as they run to their effector cells.
    • The parasympathetic system is characterized by long pre-ganglionic fibers that run to ganglia that are far from the spinal cord.
      • Subsequently, the post-ganglionic fibers of parasympathetics are short fibers that run to effector cells that are close to their ganglia.
[edit] Structures
  • Be able to find:
    • White matter
    • Grey matter
    • Dorsal, ventra, and lateral horn
    • Ventral root
    • Dorsal root
    • DRG
    • Multipolar motor neurons (ventral horn)
    • Axon hillock
    • Nissl bodies
    • Neuroglia
    • Neurophil

[edit] Dorsal Root Ganglion

[edit] Slide 17
  • In slide 17 one can see a dorsal root ganglion attached to the spinal cord.
  • The dorsal root ganglion holds cell bodies of sensory neurons.
  • These sensory neurons give off only one process, but it quickly splits into two.
    • This is called pseudounipolar.
    • One process heads to the spinal cord via the dorsal root, then horn.
      • This process will synapse in the spinal cord with a neuron that will transduce the signal up the spinal cord.
    • One process heads to the effector sensory cell.
  • These sensory cells can be carrying either somatic or visceral sensory input.
  • Sensory cells of the dorsal root ganglia are highly active and therefore have large nuclei, lots of euchromatin, and prominent nucleoli.
    • Furthermore, they have lots of supporting cells surrounding them: satellite cells.

Look also for myelinated nerve fibers within the ganglion.

  • Be able to identify:
    • Dorsal Root Ganglion
      • pseudounipolar somatic and visceral afferent ("at" the CNS) fibers.
    • Ventral horn
      • Multipolar somatic efferent ("exit" the CNS) fibers.
    • Lateral horn
      • Multipolar visceral efferent ("exit" the CNS) preganglionic fibers
      • Multipolar visceral efferent ("exit" the CNS) postganglionic fibers
    • Vertebral ganglion.
    • Prevertebral ganglion.


[edit] Autonomic Ganglion

[edit] Slide 12
  • This slide is of the sympathetic ganglia, which is part of the autonomic nervous system.
  • Nissl stain and lipofuscin were used:
    • Nissl causes rER to stain pink
    • Lipofuscin gives cells a brown color
  • Recall that ganglia are where post-synaptic cell bodies reside and synapse between pre-syn and post-syn neurons occurs.
    • More specifically, because this is a sympathetic ganglia, short pre-synaptic fibers are synapsing upon bodies of long post-synaptic cells.
    • And because this is a sympathetic ganglion, these neurons are visceral motor neurons.
      • These will be efferent ("exit" the CNS) fibers.
  • Sympathetic, visceral, post-synaptic motor neurons are:
    • Multipolar
      • But it is harder to see their processes than with the somatic motor neuron bodies of the ventral horn (which are also multipolar).
  • Neurons in the sympathetic ganglion are surrounded by satellite cells.
    • However, these satellite cells are not as numerous or tightly packed as those that we saw surrounding the neurons in the DRG (slide 17).
  • One should also be able to identify myelinated and unmyelinated axons passing through the sympathetic ganglion.

[edit] Miscellaneous

  • Osmium tetroxide preverves lipids (like those of myelin).
    • Makes adiposites dark black because of all the lipids they hold.
    • Makes myelin brownish around the axon of neuron.
  • The three-neuriums are all connective tissue.
    • Endoneurium is the most delicate.
    • Epineurium is coarse connective tissue.
    • Perineurium surrounds the nerve and projects deep into the bundle of axons where it blends with the endoneurium.


  • stopped here on 01/07/11 at 2:15PM
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