Tissue Bio: Lecture 13-14: Nervous System

What is the appearance of oligodendrocytes in microscope?

*small cells with condensed nuclei and cytoplasm that does nto stain in H+E d/t abundant Golgi *In image, see that they are located fairly close to neurons, look for white material around nucleus b/c extensive golgi, which won't stain - not a lot of rER

Describe membrane potentials and nerve impulses

*symmetric distribution of sodium (high extracellular) and potassium (high in cytoplasm) across plasma membrane of all parts of he nerve, producing a resting membrane potential (-65 mV) (cell is more negative than surroundings) *when Na channels open, Na rushes in and local membrane potential becomes +30 mV *remains depolarized until sodium pumps push sodium back out and bring potassium back in *depolarization moves like a wave from one end of the neuron to another

What are ependymal cells? What is their function? Appearance in microscope?

*technically not an epithelium b/c epithelia sit on basement membrane and these have projections that dig into neuropil, etc. - they try to anchor to astrocytes *function = produce CSF *these cells are full of fluid so they are important for shock-absorption purposes *found in 1 special region of the brain (ventricle) [*make up the lining of the ventricles of the brain or the central canal of the spinal chord *function = produces cerebral spinal fluid in the ventricles *low columnar ciliated epithelial-like cells that may have cilia or microvilli on apical surface, lack a basement memrane (instead, the basal portion branches directly onto other cells)]

What are oligodendrocytes?

*type of glial cell *Function = improves conduction of electrical impulses by providing insulation of axons *cell with long myelin-producng processes that surround axons of the CNS *can myelinate up to 50 axons [Note: oligodendrocytes are specific to CNS; whereas, Schwann cells are specific to PNS - producing myelin around axons]

Describe the cell body of a neuron. Also called?

also called "soma" or "perikaryon" *produces proteins needed in processes, usually large + centrally located euchromatic nucleus and prominent nucleolus *cytoplasm rich in rER, free polyribosomes (nissl substance) and golgi

What are the nodes of ranvier?

areas where myelin sheaths from two Schwann cells come together leave a small gap where the axon is exposed -- in this exposed area (node), the sodium channels and other depolarizton components are concentrated so that depolarization essentially jumps from node to node, making depolarization event much, much faster

Describe appearance of astrocytes in light microscopy.

microscopic appearance = small cell with elongated oval nuclei and very little cytoplasm *longer fibers in white matter and shorter processes in gray matter *in this particular stain, see neurons and then find ovals around --> slightly larger = astrocytes, contrast to smaller + darker

What is myelin?

multiple wrappings of plasma membrane extensions of cells around axons *myelin is extension of oligodendrocytes in (CNS) and extensions of schwann cells (PNS) *extensions are composed primarily of plasma membrane and very little cytoplasm *plasma membrane is comprised of >90% lipid and very little protein *the few proteins that are present are often source targets in auto immune diseases *proteins that are present are often myelin basic proteins that anchor the layers of the plasma membrane together

Microscopic appearance of schwann cells

oval nuclei and are associated with nerves (in EM - schwann cells are seen associated with axons) (also see fibroblasts in this image, they are the longer and more flat nuclei)

See diagram of meninges

see outside = skin of scalp --> periosteium --> bone of skull (thicker) --> dura mater --> arachnoid --> pia mater --> cerebral corex + white matter

light microscopy image of myelin

see white spaces where lipid exists as part of myelin but has been extracted in staining process

Describe an axon. What is its function?

single long process (up to 1 M in length) with constant diameter, does not branch until it is a great distance from the cell body Function = sends impulses to other cells *lacks rER or polyribosomes + requires protein from cell body *includes sER, mitochondria, vesicles, microtubules, bundles of intermediate filaments

Appearance of satellite cells in microscope

small + rounded, sometimes flattened nuclei around neuronal cell bodies in the ganglia, cytoplasm is indistinct *also notice that the neuronal cell bodies have lots of lipofusin b/c neurons are often longer lived cells

Microscopic appearance of microglia

small cells with dense + elongated nuclei *relatively rare cells *essentially macrophages (not good if lymphocytes are int he brain b/c will destroy neurons) - part of innate immunity in brain

What are satellite cells?

small glial cells with thin cytoplasmic extensions that surround the cell bodies of neurons in the ganglia, most numerous cells in the ganglia (type of glial cell that insulates and nourishes) **PNS **function = insulation, nourishment, regulation

Stain of node of ranvier

trichrom see lines perpendicular to axons - here stained blue, can see the breaks

General properties of the blood brain barrier?

*large molecules do not pass through the BBB easily. *Low lipid (fat) soluble molecules do not penetrate into the brain. However, lipid soluble molecules, such as barbituate drugs, rapidly cross through into the brain. *Molecules that have a high electrical charge are slowed

see astrocytes

*likely from white matter, larger but less darkly stained, see more oval shaped nuclei

What are microglia?

*microglia = small, irregular cells with numerous thin processes that are highly mobile cells capable of migrating through the neuropil *Function = act as phagocytic cells related to monocytes and are main immune defense in CNS

EM of synapse

** see most common feature of the synapse = many secretory vesicles, not gigantic but fairly small -- see smaller circles, loaded with neurotransmitters + have lots of mitochondria b/c process takes lots of energy

CNS v PNS

*CNS consists of the brain and spinal cord, while the PNS includes all other nervous system tissue *All sensory receptors, sensory neurons and motor neurons are part of the PNS *The bones of the skull and spinal vertebrae encase all CNS neurons *Neurons in the PNS are not encased in bone; rather, they travel through or lie on top of muscle, organ and skin tissue. *Groups of neurons form in both the CNS and the PNS. In the CNS, a group of neurons is called a NUCLEUS. In the PNS, a group of cell bodies is known as a GANGLION, while a bundle of neuron tracts is called a NERVE.

Describe the CT involved in a nerve

*Note: nerve = bundle of axons (note: axons are still myelinated) covered by glia and CT *The CT that encloses each individual axon = ENDONEURIUM [CT that contacts the axon, Schwann cell + myelin and some loose CT] PERINEURIUM = unique layers of CT that wraps many axons into bundles, called fascicles - the fascicles form a partial blood-neuron barrier b/c of tight junctions (essentially forming a blood-nerve barrier) - can't give drugs to nerves so much b/c must diffuse through the perineurium and the epineurium EPINEURIUM = CT sheath that binds the outside of the nerve - fibroblasts ;lots of type I collagen, so will see fibroblasts producing this ECM that is rich in type I *note: sometimes, you just have 1 fasicle but you will always have 3 layers, so in that case, the perineurium and epineurium will sort of sit on top/ beneath one another

What is the relationship between the presynaptic terminal and the postsynaptic terminal? What are the two types of stimulation for the postsynaptic terminal receptors?

*Presynaptic terminal (terminal bouton) - has many secretory vesicles filled with neurotransmitters, has many mitochondria, sER reervoir of membrane, synthesizes neurotransmitters, adhesion plaque-like structures *Postsynaptic terminal receptors for neurotransmitters are stimulated by ... **depolarization and nerve impulses (excitatory) OR **hyperpolarization (inhibitory)

Main cells/ structures covered for PNS

*Schwann cells (neurolemmocyte) [multiple wrappings of plasma membrane around axons in PNS] *Ganlia [group of neuronal cell bodies + associated glia outside CNS] (group of nerve cell bodies located in PNS) *Satellite cells [surround cell bodies of neuron in ganglia to nourish/ regulate] *Node of Ranvier/node [myelin sheath from 2 schwann cell comes together + forms a gap] *Nerve (enclosed, cable-like bundle of nerve fibres called axons in PNS) [analagous structure in CNS = nerve tracts]

What are dendrites? function? Characteristics?

-thin processes that branch many times and many are often present on a single neuron -Function = to receive impulses -they have spines where synapses occur with axons (can be connected to hundreds of other neurons)(note neuronal plasticity, spines are not fixed) - have same components as the cell body but DO NOT HAVE GOLGI [note that axons play a large role in secreting -ex, neurotransmitters - so need to produce secretory vesicles, so they need golgi]

There are three types of neuron/ neuron synapses. What are they?

1. Axosomatic synapse [axon --> cell body] 2. Axodendritic synapse [most common, axon --> dendritic spine] 3. Axoaxonic synapse [axon --> axon, synapses on a branch + regulate whether or not the other axon will communicate]

What is the organization of the nervous system?

1. CNS = brain and spinal chord 2. PNS = consists of cranial spinal and peripheral nerves that conduct impulses to and from the CNS (motor and sensory nerves) as well as ganglia

There are two types of synapses. What are they?

1. Electrical synapses = impulse conducted by gap junctions 2. Chemical synapses = impulse conducted by a neurotransmitter, more common - depolarizaton event is communicated by release from secretory vesicles of neurotransmitters (amines, amino acids, small peptides)

In an axon, proteins are shipped down in vesicles and carried along microtubules. Contents can be carried in two ways. What are they? Describe the two ways.

1. anterograde transport: molecules/ organelles transported down the axon and mediated by kinesin on microtubules 2. retrograde transport: molecules/ organelles transported back to the cell body, mediated by dynein on microtubules **specialized processes of glial cells cover axons

We can name neurons based on their shapes and how many dendrites and axons they have. What are the three most common types of neurons + one?

1. bipolar (interneuron) 2. unipolar (sensory neuron) 3. multipolar (motoneuron) 4. Anaxonic neurons

Describe the 4 general "steps" of myelination by schwann cells

1. neurolemmocyte starts to wrap around a portion of an axon 2. neurolemmocyte cytoplasm and plasma membrane begin to form consecutive layers around the axon 3. overlapping inner layers of the neurolemmocyte plasma membrane form myelin sheath (see cytoplasm of the schwann cell and then myelin sheath inner wrappings) 4. eventually, the schwann cell cytoplasm and nucleus are pushed to the periphery of the cell as the myelin sheath is formed

What are the functions of astrocytes (note: don't necessarily need to memorize)

1. produce growth factors for neurons [neurons are addicted to growth factors that they can't make themselves (in CNS), will die w/out it --> apoptosis] 2. facilitate neuronal migration during development 3. control the ionic environment of the neuron [important in estabilishing clear-cut depolarizaton that exists for sodium and potassium across membrane] 4. produce processes called perivascular feet that form blood brain barrier (regulate vasocilation and transfer oxygen and nutrients to neurons) 5. produce expanded processes that form the glial limiting membrane 6. produce metabolites for neurons + absorb excess neurotransmitters [conduit for oxygen + nutrients and waste that neurons need, produce many key metabolites for neurons] 8. communicate with one another through gap junctions between processes 9. after injury, proliferate to form a glial scar [this is an issue in spinal cord injury b/c after destructon of axons, area is filled by astrocytes that form a barrier that axons can't pass, contribute to the current irreversibility of paralysis]

Function of blood brain barrier?

1. protects brain from "foreign substances" in blood that might injure the brain 2. protects the brain from hormones and neurotransmitters in the rest of the body 3. maintains a constant environment for the brain

What are the functions of the nevous system?

1. receive stimuli from inside and outside of body 2. analyzes stimuli 3. produces coordinated responses to stimuli

What is a nerve? What is an axon? What is true of axon size and conduction velocity?

A nerve is like a bundle cable - it is axons covered by glia and connective tissue Axon = cytoplasmic extension enriched in microtubules and neurofilaments the greater the size of the axon, the greater the conduction velocity

What is an astrocyte?

Astrocyte = one particular "glial cell", means "star" in French, looks like a star though you can't distinguish this shape will in H+E *cell with a smaller cell body and numerous processes of various lengths, these fibers are generally longer in white matter and shorter in grey matter

Where would you find RER but not Golgi? A. Soma B. Dendrite C. Axon D. Axon hillhock

B. Dendrite (axon lacks rER, dendrites lack golgi, soma has both)

In neurons, what organelle is described as Nissl substance? A. smooth endoplasmic reticulum B. rough endoplasmic reticulum C. the nucleus D. mitochondria E. microtubules

B. rough endoplasmic reticulum

How do we now understand the blood brain barrier?

BBB is semi-permeable - allows only some materials from blood to enter brain *in most parts of body, capillaries are lined with endothelial cells, which can (and often do for most parts of body) have small spaces between to allow substances to readily move between the inside and outside of the vessels *in brain, endothelial cells fit tightly together and substances are not allowed to pass out of the bloodstream (some molecules, like glucose, are transported out of the blood by special methods) *glial cells (astrocytes) form a layer around the brain blood vessels and are likely important in the development of the blood brain barrier (astrocytes also might be responsible for transporting ions from the brain into the blood)

Describe bipolar neurons and unipolar neurons. Where are they located?

Bipolar = single dendrite on one end, axon on the other end of the cell body (usually sensory neurons)(interneuron) **located in retina, olfactory mucosa, ear Unipolar = axon and dendrite arise from the same extension from the cell body (sort of functions as a dendrite and an axon, mostly for touch - synapse with other cells with more axonal phenotypes) **located in spinal chord sensory nerves

Describe the blood brain barrier in regards to astrocytes. Start by describing the general blood supply to the CNS.

Blood supply to the CNS: arteries and veins that penetrate the brain are surrounded by pia mater, which disappears around the capillaries *capillaries are surrounded by foot processes of astrocytes *brain has continuous capillaries, which have endothelial cells with many tight junctions and little transcytosis, meaning that exchange requires diffusion through the cytoplasm, basement membrane, and astrocyte foot processes to be accessible to neuronal cell bodies or processes

Which of the following is true about regeneration of axons in the PNS after nerve injury? A. It does not require the nerve cells to remain alive B. It requires microglia C. It occurs by a mechanism that is dependent on the proliferation of Schwann cells D. It occurs in conjunction with degeneration and phagocytosis of neuronal cell bodies E. It requires that the myelin sheath remain intact

C. It occurs by a mechanism that is dependent on the proliferation of Schwann cells

What is the difference between the CNS and PNS?

CNS = spinal cord and brain, connected to PNS which includes the nerves in our extremities *neurons in CNS and PNS differ (for example, in their ability to regenerate) *both PNS and CNS have different support cells (called glia cells) (glia is ancient Greek name for glue)

Summary of nervous system

CNS: *nerve cell is key to major nervous system functions understand the organelles present in the dendrites axons and the cell body *recognized by patterns of gray and white matter, neuronal cell bodies easily recognized but supported by many glial cells which are more difficult to distinguish PNS: *based on nerves organized with 3 CT layers + ganglia where neuronal cell bodies located

11. The major chemical component of myelin is? A. DNA B. protein C. RNA D lipid E. Carbohydrate

D. Lipid

12. Which cell is responsible for myelinating axons in the peripheral nervous system? A. astrocyte B. satellite cell C. microglia D Schwann cell E. Oligodendrocyte

D. Schwann cell

Gray matter would best be defined as A. areas of the CNS rich in myelinated axons B. the connective tissue covering of the brain C. the lining of the ventricles D areas of the CNS with abundant cell bodies of neurons and glia E. groups of neuronal cell bodies located outside the CNS

D. areas of the CNS with abundant cell bodies of neurons and glia

11. The major component of myelin is? A. DNA B. protein C. RNA D lipid E. Carbohydrate

D. lipid

Describe the layers of the meninges.

Dura mater = tough layer essentially continuous with inner periosteium of skull bones Arachnoid mater = spongy layer filled with CSF, cobweb like strands of CT connect this to the other 2 layers around it Pia mater = thin layer of collagen and elastic fibers and the occasional fibroblast that forms the inner-most layer of the meninges, formed on a basement membrane, which is produced from astrocyte processes (formed on top of foot processes of astrocytes that support it)

In a routinely prepared H&E stained section, what would be the appearance of an oligodendrocyte? A. Basophilic cytoplasm B. eosinophilic cytoplasm C. cell with many lipofuscin granules in the cytoplasm D. cell with abundant rough endoplasmic reticulum E. cell with very little staining of the cytoplasm

E. cell with very little staining of the cytoplasm

In a routinely prepared H&E stained section, what would be the appearance of an oligodendrocyte? A. Basophilic cytoplasm B. eosinophilic cytoplasm C. cell with many lipofuscin granules in the cytoplasm D. cell with abundant rough endoplasmic reticulum E. cell with very little staining of the cytoplasm

E. cells with very little staining of the cytoplasm

PNS vs CNS in neuronal regeneration

If the process of a neuron is severed, the part without the cell body will degrade and the part with contact to the cell body will lost its insulation sheet at the site of injury and start building new processes to find back its "old" contact sites *In PNS: reestablishing connections works rather well b/c regenerating neurons receives lots of support: scavenger cells from immne system remove debris from old isolation material + excrete molecules which encourage Schwann cells to participate --> schwann cells excrete growth factors --> build back to re-establish connections *In CNS: when spinal cord is injured, immune and glial cells react but their signals are not supportive - these cells make the damage worse -debris takes longer to clear (inhibiting repair mechanisms) -oligodendrocytes do not rejuvenate or secrete growth factors like schwann cells - astrocytes form a dense scar that young neuronal processes cannot penetrate

What is the meninges? What are its three main components?

Meninges = CT covering the brain and spinal chord *made of 3 main layers = dura mater, arachnoid mater, pia mater

Describe multipolar neurons and pyrimidal cells. Where are they located?

Multipolar = multiple dendrites form cell body and single axon extends from cell body, very common throughout CNS + also just very common in general Anaxonic = lacks axons and does not produce action potentials, regulates local electric charges of surrounding neurons -- [nothing but dendrites, no axon - sink off depolarization from other large neurons, fairly complex] **present in the retina

neuroregeneration Describe the process of axonal regeneration

Nerve processes can be redily regrown (though can be prevented by glial scaring, etc.) Axonal regeneration = 1. Destructive phase (process distal to injury site and glia degenerate), chromotolysis [the dissolution of the Nissl bodies in the cell body of a neuron] 2. Inflammatory phase (macrophages come in and induce inflammation + have incredible healing powers) 3. Glia cell proliferation = glia cells proliferate (cytokines) [cells proliferate and restore the pathway that the axon took] 4. glial cell guidance of regrowing processes (neurotrophins) -- produce guidance molecules for axons to reconnect

Describe the organization of the PNS/ CNS in this lecture (weird question, yanno)

Neuron (in both PNS and CNS) CNS: Glial cells CNS: macro structures PNS: Glial cells *Nerves *Ganglia *regeneration of nervous tissue

What is the situation with neuronal repair?

Neurons = terminally differentiated and incapable of reentering the cell cycle Neural stem cell = *discovered in hipocampus - multipotent cells capable of giving rise to both neurons and glial cells - typically quiescent but upon injury, they re-enter the cell cycle, but few cells differentiate into mature neurons or integrate into circuits Though neurons are sparsely repopulated, nerve processes (axons in the PNS) do regenerate more readily - after injury, axons and dendrites (nerve processes) can be regrown ... though this can be prevented by various types of scaring *SO, we can get axonal regeneration *distal degeneration is driven by macrophages (incredible healing cells) (inflammatory phase) that come in and proliferate --> restore the pathway that the axon took, producng guidance molecules for axons to reconnect

What are the basics of early understanding of blood brain barrier?

Over 100 years ago, it was discovered that if blue dye was injected into bloodstream of an aniaml, that tissue turned blue -- true for all tissues except brain ... scientists thought that a "Blood-Brain-Barrier" existed that prevented material from blood from entering brain

What are schwann cells?

PNS *glia of PNS that support nerve processes Function = produce a sheath around the axon to enhance transmission of nerve impulses, trophic support (trophic = relating to feeding/ nutrients)

Describe Schwann cells ... + also called?

Schwann cells are also called neurolemmocytes There are 2 types of Schwann cells 1. unmyelinated (axons just exist in the cytoplasm of the schwann cells) - axon is located in a cleft within the Schwann cell cytoplasm 2. myelinated (1 axon and 1 schwann cell) - axon is wrapped in several layers of a plasma membrane extension of the Schwann cell, similar to what was discussed with oligodendrocytes See image of unmyelinated axons in schwann cells:

Describe spines in the dendrites. What is the function of spines?

Spines are little projections from the dendrites that are the site of synapses with axons They are a key site involved in neuroplasticity b/c spines and their synapses can be rapidly lost

Main cells/ structures covered for CNS

astrocytes (universal helper cell) microglia (responsible for immune response, phagocytic cells) oligodendrocytes (ensure insulation of neurons) - multiple wrappings of plasma membrane around axons in CNS Ependymal cells (line ventricles of brain and central canal of spinal chord) choroid plexus (has modified ependymal cells to secrete CSF in the brain ventricles) Gray matter (lots of neurons + glia + neuropil - lots of dendrites and astrocytes) White matter (rich in myelinated axons) CT covering brain + spinal chord = dura mater, arachnoid, pia mater

What is the neuron?

elongated excitable cells, receive and transmit depolarization impulses

What is the choroid plexis? What is the function?

extensions of pia mater into the ventricles lined with ependymal cells function = transports water and some ions into cerebral spinal fluid within ventricle *fluid and it flows from ventricles to central canal into the arachnoid layer where it is taken up by venous circulation [The choroid plexus is a plexus of cells that produces the cerebrospinal fluid in the ventricles of the brain. The choroid plexus consists of modified ependymal cells.]

The other cells of the nervous system (besides neurons) are called ...

glial cells (general name for all cells that are not neurons)

Describe the tissue types in the CNS

grey matter = areas of CNS rich in cell bodies of neurons and glia neuropil = areas rich in dendrites and projectoins of astrocytes (non-myelinated processes), relatively few cell bodies - this is where synapses occur white matter = areas of CNS rich in myelinated axons [Grey matter = consists of neuronal cell bodies, neuropil (dendrites and myelinated as well as unmyelinated axons), glial cells (astrocytes and oligodendrocytes), synapses, and capillaries -- neuropil typically not thought of being part of white matter]

Describe the portions of an axon

hillock = base of axon attached to cell body initial segment = down from the hillock where stimuli are algebraically summed for decision propogate depolarization ["decision making zone", determines whether or not to send a signal, if dendrites w/ 100s of connections, many are depolarized but that doesn't mean an axon will send the signal, this zone determines whether or not the signal will be propogated further]