Microanatomy

Question 1

Cells within the CNS

Answer 1

• Neurons
• Glia: astrocytes, oligodendrocytes, microglia
• Ependymal cells (of the choroid plexus): simple cuboidal epithelium
• Endothelium
• Cells of the meninges
• Little ECM in the CNS, instead up to 20% of the volume of the brain is CSF
• Accumulation of water results in cerebral edema

Question 2

Grey vs white matter

Answer 2

• Grey matter contains neuron cell bodies, as well as glial cells, axons, and dendrites
• Neuropil is the fiber rich region btwn cell bodies (contains dendrites, axons, glia)
• Grey matter is on the inside of the spinal cord (butterfly shape) and on the outside of the brain (cortex)
• White matter contains long-distance myelinated axons, astrocytes and oligodendrocytes
• White matter is on the outside of the spinal cord and the inside of the brain

Question 3

Neurons

Answer 3

• Cell bodies have a large euchromatic nucleus w/ prominent nucleolus (active protein synthesis)
• Also contain lots of RER and polyribosomes (Nissl bodies)
• Axon hillock and the rest of the axon is devoid of nissl bodies
• Dendrites and spines have nissl bodies in proximal areas (to soma)
• Retrograde transport provides a point of access for toxins and viruses into CNS

Question 4

Classification of neurons

Answer 4

• Number of processes: can be unipolar (like in DRGs: have one long axon continuous w/ dendrites), bipolar (one long dendrite, then cell body, then axon), or multipolar (typical neuron, many dendrites off the body to one axon)
• Arrangement of processes
• NT type
• Shape of cell body, direction of transmission, location in body

Question 5

Synapses and spines

Answer 5

• Presynaptic cell has vesicles to store NTs, and the active zone which is the site of vesicle fusion and NT release
• Postsynaptic component can be found on dendrites (axo-dendritic synapse), cell bodies (axo-somatic), or axons (axo-axonic)
• The postsynaptic area (postsynaptic density) contains the NT receptors
• Spines are branches off dendrites that accept presynaptic input (majority of excitatory synapse location), are involved in learning
• Abnormal spine morphology/# are hallmarks of neurological diseases like fragile X and AD

Question 6

Synaptogenesis

Answer 6

• Formation of new synapses
• Most neurons are generated prior to birth
• Synapse # increases over the first few years of like, followed by a period of pruning
• During pruning the synapse # can fall by 50%
• The increase in synapse # reflects more connections, not more neurons
• Likewise, the growth of brain size early in life is due to an increase in dendritic processes, not in neuron #

Question 7

Glia cells

Answer 7

• 3 classes in the CNS: astrocytes, oligodendrocytes, microglia
• Play many important roles in normal CNS function, including structural support

Question 8

Astrocytes 1

Answer 8

• Stellate cells that express glial fibrillary acidic protein (GFAP) and are connected to each other by gap junctions
• Regulate the ECF by adjusting ion concentration and clearing excess glutamate (which could cause harm to neurons)
• Since neurons have limited ability to combat ROS, astrocytes are required to couple w/ neurons and prevent oxidative stress-induced cell death
• Also store glycogen

Question 9

Astrocytes 2

Answer 9

• Have processes that ensheath the synapse, and play a role in synaptic formation/remodeling
• Astrocyte processes can terminate in endfeet to form the layer glia limitans at the brain surface and around blood vessels
• Neuron activity triggers the release of vasoactive substances by astrocytes to increase blood flow to the region due to the higher metabolic demand

Question 10

Reactive gliosis

Answer 10

• Hypertrophy of the cell body of astrocytes, increase growth of processes, expression of GFAP, and proliferation
• This can serve to limit the extent of neuronal injury and enhance neuronal survival
• But this can also lead to edema, inflammation (release of cytokines), and/or form a glial scar that inhibits axonal regeneration

Question 11

Oligodendrocytes (OD)

Answer 11

• Responsible for myelin formation in CNS (schwann cells responsible for myelin in PNS)
• Unlike schwann cells, a single OD can myelin ate multiple axons
• The process of myelination is not complete in the prefrontal cortex until the third decade in life
• Demyelinating disorders (MS, transverse myelitis) can be cause by genetic factors, infections, AI rxns, and the environment

Question 12

Microglia (MG)

Answer 12

• Resident macrophages (smallest glial cells in the brain)
• Identify and phagocytose infectious agents in the CNS, remodel local environment, and participate in synaptic pruning
• Following injury they are responsible for the removal of dying cells and cellular debris

Question 13

BBB 1

Answer 13

• Endothelial cell tight junctions form the BBB, preventing large or hydrophilic molecules from exiting the blood
• Hormones, O2, and CO2 can still freely diffuse, and molecules needed for function (glc, AAs) are transported across the endothelium
• Endothelium in the CNS have high abundance of mito
• Astrocyte endfeet are not part of the BBB, but early on in development they induce the formation of the tight junctions

Question 14

BBB 2

Answer 14

• BBB protects the brain from most common bacterial infections, except syphilis and lyme disease
• BBB becomes more permeable during times of inflammation
• In certain regions (circumventricular organs) the BBB is interrupted
• This is to allow the brain to respond to chemical changes in the blood and to secrete neuropeptides into the blood

Question 15

Circumventricular organs

Answer 15

• The median eminence and neurohypophysis are involved in the regulation and release of pituitary hormones
• The area postrema (located in the medulla) contains chemoreceptors to trigger vomiting (can also detect bacteria and drugs)

Question 16

Ependymal cells and choroid plexus (CP)

Answer 16

• Ependymal cells are simple cuboidal epithelium that line the ventricles
• They contain cilia on the surface to assist in the circulation of the CSF
• The CP (producer of the CSF) is found within the ventricles
• The CP is a layer of ependymal cells surrounding richly vascularized connective tissue
• The tight junctions btwn the ependymal cells form the basis of the blood-CSF barrier (distinct from BBB which is due to tight junctions of the endothelial cells)
• Ependymal cells actively transport Na, Cl, and HCO3 into the CSF
• CSF removes metabolic waste and maintains the CNS environment at optimal levels

Question 17

Histology of the cerebellum

Answer 17

• The grey matter can be divided into 2 layers: the molecular (outer) and the granular (inner) layers
• The molecular layer contains stellate and basket (small) neurons, with lots of neuropil
• The molecular layer contains a high density of granule (small) neurons, with less neuropil
• Purkinje cells (only in cerebellum) are found at the border of the molecular and granular layers, and extend their axons into the molecular layer
• Large pyramidal cells can be found near the middle of the gray matter in the CEREBRAL cortex