Histology of the nervous system

Granule (stellate) neurons

o Granule (aka: stellate) neurons are difficult to distinguish from neuroglia with H&E stain, but they congregate as two layers among the other layers of cortex.

Pyramidal neurons

o Pyramidal neurons have large triangular cell bodies with Nissl bodies (RER), large euchromatic nucleus with prominent nucleolus, and large dendrites (a few basal dendrites and a single apical dendrite.

Peripheral ganglia

- Also referred to simply as ganglia, these aggregation of neuronal cell bodies are located in the PNS and can be either sensory or autonomic.

injury response

- Although neurons are typically unable to proliferate, they can regenerate cellular processes. So, if an entire neuron in the CNS was damaged, that is a permanent loss. Damage to a nerve fiber in a peripheral nerve of the PNS, however, may be repaired. - A neuron responds to an injury through a series of events that includes degeneration and regeneration. The cells that are involved in these responses are neurons, Schwann cells, oligodendrocytes, macrophages, and microglia.

Autonomic ganglia

- Autonomic ganglia are considered to function in a motor capacity as they cause contraction of smooth or cardiac muscle as well as glandular secretion. - In the sympathetic nervous system, the autonomic ganglia are located in the sympathetic chains on either side of the vertebral column (and the collateral ganglia alongside the abdominal aorta). Preganglionic sympathetic neurons synapse on postganglionic sympathetic neurons in the autonomic ganglia. These postganglionic sympathetic neurons will often join peripheral nerves after exiting the ganglia and terminate at their effector organ. - In the parasympathetic nervous system, the autonomic (terminal) ganglia are located in a region of the head or the wall of the organ. The preganglionic parasympathetic fibers originate within a cranial nerve or a segment of the sacral spinal cord and synapse on postganglionic parasympathetic neurons in the autonomic ganglia. The postganglionic parasympathetic fibers terminate at their effector organ.

Central nervous system injury and repair

- Due to the blood brain barrier, there is limited infiltration of macrophages and the removal of cellular debris is slow. The number of microglia in the area of injury do increase, but they are just not as efficient as macrophages. The presence of these myelin fragments for a long period of time are thought to interfere with the regeneration of the axon. - When areas of the CNS are damaged, astrocytes are recruited to the area and create cellular scar tissue known as a glial scar to fill the space left behind by the degenerated axon.

Nodes of Ranvier

- Gaps along the axon between adjacent Schwann cells, known as nodes of Ranvier, occur at discrete intervals alternating with internodal segments where the Schwann cells are wrapped around the axon. The external lamina of the Schwann cell follows the cell membrane down to the nodes of Ranvier and is continuous among the adjacent Schwann cells. - The plasma membrane at the Nodes of Ranvier is heavily populated by voltage-gated Na+ ion channels that participate in depolarization of the membrane during neuronal transmission. This allows the action potential to "jump" from node to node in a process called saltatory conduction. The internodal segments contain very few ion channels.

pseudounipolar neurons

- Have just one process extending from the cell body, which later splits into two branches. The central branch is directed towards the CNS and the peripheral branch proceeds within the PNS. - Both the central and peripheral branches are axonal in nature, though the terminal end of the peripheral branch splits into dendrite-like processes. During the transmission of an action potential, an impulse traveling through a pseudounipolar does not need to pass through the cell body, but will continue from the peripheral process directly to the central process. - Unipolar neurons can be found in the dorsal root ganglion as well as some of the ganglia of cranial nerves.

Multipolar neurons

- Have multiple dendrites that project from the cell body and a single axon. Multipolar neurons are the most common type of neuron and are present all throughout the nervous system. - Subcategories of multipolar neurons are identified based on the shape of their cell body, such as pyramidal neurons or named after the scientist credited for their discovery, such as Purkinje cells.

Bipolar neurons

- Have two processes projecting from the soma, one dendrite and one axon. - Bipolar neurons are commonly observed in specialized sensory structures, such as the olfactory epithelium in the nasal cavity as well as the cochlea and vestibule in the inner ear.

Schwann cells location

- Located only in the PNS

Satellite cells

- Located only within the PNS, satellite cells surround neuronal cell bodies in ganglia, providing structural and metabolic support. These cells form a layer around a single cell body in the ganglia of the PNS to insulate, nourish, and regulate the microenvironment. Their function is similar to Schwann cells, though they do not produce myelin. - In an H&E stained section of a ganglion, the nuclei of satellite cells are observed surrounding each cell body. In order for an axon to synapse on the cell body of a neuron in the ganglia, it must be permitted to pass through this layer of satellite cells.

ependymal cells

- Low columnar to cuboidal cells in the CNS that line the ventricles of the brain and central canal of the spinal cord. In some areas, ependymal cells are ciliated to promote the circulation of CSF. - Unlike a typical epithelium, ependymal cells do not sit on a basal lamina, instead the basal sides of these cells extend into the surrounding neural tissue. - Ependymal cells in the ventricles can also be modified to form part of the choroid plexus, where CSF is secreted and maintained.

Peripheral nerve injury and repair

- Neurons have a significant influence on the cells that they contact. If a neuron is damaged, the target tissue had been in contact with will atrophy and degenerate. Upon injury, the neuron initiates the attempt to repair the damaged process, regenerate it, and restore signaling through the neuron. The collective events that occur during the - endeavor to restore this function is called the axon reaction. This consists of structural and metabolic changes at the injury site, distal (anterograde) to the injury site and proximal (retrograde) to the injury site that may occur simultaneously or weeks, even months, apart. - At the site of injury, cytoskeletal elements such as microtubules and neurofilaments disassemble at the severed ends of the axon and they retract away from each other. The open ends of the membranes fuse together and macrophages invade the area to remove debris and fibroblasts are also recruited. The ends of each of the axons start to expand back towards each other.

Microglia

- Phagocytic cells located in the CNS, microglia function to clear debris from the surrounding tissue and protect the nervous system from pathogens and tumorigenic cells. These cells can also be activated to release cytokines that recruit lymphocytes. - Microglia are derived from monocytes that originate in the bone marrow and are able to migrate within the CNS, scanning the nervous tissue and removing any old or damaged tissue or pathogens.

Astrocytes

- Present exclusively in the CNS, astrocytes are the largest type of neuroglia. They largely function to regulate local ion and neurotransmitter concentrations as well as provide metabolic support to neurons. - Astrocytes are characterized by the presence of cytoplasmic bundles of intermediate filaments made up of glial fibrillar acidic protein (GFAP). GFAP is commonly used in research as an astrocyte marker in tissue sections from the CNS. - Astrocytes are integral components of the blood-brain barrier, the structure of which will be discussed in greater detail later in this handout.

Anaxonic neurons

- Present in the CNS, anaxonic neurons do not have true axons and will not produce action potentials. These neurons instead function to regulate electrical changes in nearby neurons.

Oligodendrocytes

- Present the CNS, oligodendrocytes provide electrical insulation to neurons by forming the myelin sheath. - The myelin sheath formed by oligodendrocytes functions similar to that observed in the Schwann cells of the PNS, though a single oligodendrocyte can myelinate multiple axons. Unlike Schwann cells, the myelin lamellae of oligodendrocytes do not contain any cytoplasm. - The processes of the oligodendrocytes that extend outward from the cell body are not visible under the light microscope. They tend to stain darker than other types of neuroglia and have a relatively small nucleus.

Sensory ganglia

- Sensory ganglia are associated with some cranial nerves and each of the spinal nerves as they exit the spinal cord. The sensory ganglia associated with spinal nerves are the dorsal root ganglia, which house the cell bodies of the pseudounipolar sensory nerves. Recall that satellite cells surround the cell bodies in the ganglia. An additional connective tissue capsule containing collagen is continuous with the connective tissue (endoneurium) surrounding the peripheral nerve. The peripheral process of the pseudounipolar sensory neuron extend to the body to receive stimuli and the central process carries impulses to the CNS for processing.

Cerebellar cortex

- The cerebellum regulates balance, equilibrium, muscle tone, and muscle coordination. It receives sensory information from proprioceptors and the vestibular system (inner ears); as well as information about intended motor activities. The output through deep cerebellar nuclei and vestibular nuclei is to modify the activity of motor pathways.

Spinal cord

- The spinal cord is composed of peripheral white matter and an H-shaped center of gray matter. - The meninges of the spinal cord are continuous with those in the brain. The dura mater in the spinal cord does not associate with the spinal column, instead forming a tube of connective tissue continuous with the dura mater of the brain at the foramen magnum (where the brainstem exits the skull). The epidural space is the space between the dura mater and the wall of the vertebral canal.

Unmyelinated vs. myelinated schwann cells

- Unmyelinated axons tend to be smaller in diameter and multiple axons may be engulfed by one Schwann cell, but the wrapping associated with myelination does not occur.

CNS white and gray matter

- White matter contains primarily myelinated nerve fibers, with some unmyelinated nerves and neuroglia. It is named as such due to the white color resulting from the abundance of myelin. - Gray matter contains cell bodies, dendrites, unmyelinated portions of axons, and neuroglia. The lack of myelin makes this tissue appear gray in color. - Neuropil is the tangled aggregation of axons, dendrites, and the processes of neuroglia present around the somas. In H&E stained sections, it is often difficult to distinguish the individual components of neuropil. The cytoarchitecture of this substance can only be delineated using high-resolution electron microscopy.

White matter of the cerebral cortex

- White matter is the extensive axons, most of which are myelinated, carrying information to and from each portion of cortical grey matter. In addition to axons, white matter will contain three types of neuroglia: astrocytes, oligodendrocytes, and microglia; as well as small blood vessels and numerous capillaries.

Blood brain barrier

-A highly selective barrier between the neural tissue of the CNS and the blood that prevents the passage of specific blood-borne substances. -The capillaries in neural tissue are continuous capillaries, so diffusion and transcytosis across the endothelial cells restricts the movement of material from the blood. These capillaries are also surrounded by multiple astrocyte end-feet, creating the perivascular glia limitans, providing an additional layer restricting the movement of bacterial toxins, infectious agents, and other exogenous substances.

Gray matter of the cerebral cortex

-Can be histologically described as six distinct layers of neurons based on their morphology. Numerous types of neurons have been characterized in cortex; we will generally categorize them as pyramidal neurons and granule neurons.

Schwann cells

-Envelop and insulate axons. Axons wrapped by Schwann cells may be myelinated or unmyelinated. - During myelination, Schwann cells concentrically wrap around an axon multiple times (estimated at more than 50) to create the myelin sheath. This process squeezes out a majority of the cytoplasm and any organelles and the resulting cells have a thin, flattened nucleus. - It is important to remember here that the Schwann cell is wrapped around the axon multiple times, bringing the layers of the cell membrane of the Schwann cell in close contact with each other.

Protoplasmic astrocytes

-Present in the gray matter and are described as being stellate-shaped due to multiple branching processes emanating from the cell body. -Astrocytes will often be adjacent to blood vessels, the tips of their processes may also come into contact with the vasculature, ending at structures called pedicels (perivascular feet). -Protoplasmic astrocytes in the brain or spinal cord can also send out processes that come into contact with the pia mater, creating a pia-glial membrane. -An additional function of protoplasmic astrocytes is the regulation of the flow of cerebrospinal fluid (CSF) through the gray matter of the brain.

fibrous astrocytes

-Present primarily in the white matter of the CNS. -These astrocytes will also be closely associated with the pia mater and vasculature, but maintain a distinct external lamina.

Internal granular layer

A layer populated by small granule cells and neuroglia. This thickness of layer IV is variable from one region of cerebral cortex to another.

External pyramidal layer

Characterized by pyramidal neurons that increase in size from the external to the internal border of this layer. In many areas of cortex, layer III is relatively thick. The borders between adjacent layers are not clearly defined, but it is a broad band of pyramidal (and other) neurons.

Purkinje layer

Characterized by the presence of Purkinje cells, which are large flask-shaped cells that only exist in the cerebellum. They have highly branched dendrites which project up into the molecular layer and myelinated axons that project into the white matter. Purkinje cells integrate thousands of excitatory and inhibitory stimuli.

Granular layer

Contains small granule cell neurons, which stain dark with basophilic dye, and glomeruli (which are complex synapses among several neurons in this layer). Another type of cell, the Golgi cell, is found near the junction of the granular and Purkinje cell layers and is slightly larger than the granule cells.

Internal pyramidal layer

Contains very large pyramidal neurons and neuroglia (as well as other interneurons). These neurons have a few basal dendrites that project laterally and a large apical dendrite that projects all the way up to layer I.

Peripheral nerves

Formed by bundles of axons (nerve fibers) in the PNS. The large nerves that we name and study in Gross Anatomy are peripheral nerves. Peripheral nerves often contain nerve fibers that are sensory and those that are motor, creating mixed nerves, though purely sensory and purely motor peripheral nerves do exist.

Layers of the gray matter

I. Molecular layer II. External granular layer III. External pyramidal layer IV. Internal granular layer V. Internal pyramidal layer VI. Multiform layer

Molecular and external granular layer

I. Molecular layer This most superficial layer mostly consists of nerve terminals (axons and dendrites) that originate in other layers, horizontal cells, and neuroglia. II. External granular layer Contains granule (stellate) cells, some small pyramidal neurons, and neuroglia.

Astrocytes in nerve conduction

In the process of nerve conduction, ions such as potassium and neurotransmitters such as glutamate can pool in the neuronal microenvironment. Astrocytes remove these items, especially at the nodes of Ranvier, as they accumulate in the interstitial fluid around the neuron. Astrocytes are also capable of storing energy in the form of glycogen and releasing glucose.

Multiform layer

Made up cells that vary in shape (Martinotti cells) and neuroglia. Layer VI (similar to layer III) is difficult to clearly distinguish from layer V and the white matter.

Layers of gray matter in cerebellum

Molecular layer Purkinje layer Granular layer

Molecular layer

Present just deep to the pia mater, this layer contains stellate cells, Purkinje cell dendrites, basket cells, and unmyelinated axons from the granular layer.

Anterior and posterior horns of the spinal cord

The anterior projections of the H are the anterior horns, which contain the cell bodies of motor neurons whose axons project into the spinal nerves. The posterior horns contain interneurons that receive sensory information from neurons in the dorsal root ganglia. The central canal is continuous with the ventricles of the brain, contains ependymal cells, and contains CSF.