What type of neuron has 3 or more processes?

The dendrites are branched processes that originate from the soma and form the afferent or receptive zone of neurons. They show a similar pattern of branching in neurons with similar functions guided by the extent of interactions with afferent fibers and the activity of synapses. Functional demands may restrict, enhance, or modify the branching of the dendrites that starts during development. This neuronal plasticity can be essential in overall branching patterns and length of the dendrites. Dendrites have spines that maximize contact with other neurons, mediating excitatory and inhibitory axo-dendritic as well as dendro-dendritic synapses. They contain microfilaments and microtubules, smooth endoplasmic reticulum, ribosomes, and Golgi membrane. In more peripheral dendrites, free ribosomes and rough endoplasmic reticulum become progressively sparse and may be entirely lacking. Microtubules and microfilaments are much more conspicuous in the dendrites than in the soma and are more regularly aligned along the axis of the dendrite, forming the most striking feature of the dendrites. The microtubules are believed to be involved in the dendritic transport of proteins and mitochondria from the perikaryon to the distal portions of the dendrites.

The dendritic transport, which occurs at a rate of 3 mm/h, is comparable to some forms of axoplasmic transport. Destruction of the microtubules by drugs, such as colchicine and vinblastine, inhibits this transport. Dendritic transport may also involve viral glycoprotein that is basolaterally targeted. Dendrites contain exclusively the microtubule-associated protein (MAP-2) but do not contain growth-associated protein (GAP-43). For this very reason, MAP-2 antibodies are utilized in the identification of dendrites via immunocytochemical methods.

Axons form the efferent portion of the neurons and in general are thinner than dendrites, assuming considerable length. Compared to dendrites, axons are more uniform and contain fewer microtubules and more microfilaments but no ribosomes. Axons are longer than dendrites and may measure up to 6 feet in length, beginning from the axon hillock and giving rise to collaterals that terminate at the telodendria. They provide an avenue for transport of substances to and from the soma. Axons originate from the soma or, less frequently, from the proximal part of dendrites.

The axon is divisible into the axon hillock, initial segment, axon proper, and telodendria (axonal terminal). A clearly recognizable elevation, the axon hillock continues with the soma. The relative absence of free ribosomes and rough endoplasmic reticulum is the most obvious feature of the axon hillock. It contains a high concentration of voltage sensitive channels and is the site of the generation of action potential. In myelinated axons the initial segment extends from the axon hillock to the beginning of the myelin sheath. This segment is unmyelinated, maintains inhibitory axo-axonal synapses, and contains some microtubules, neurofilaments, and mitochondria but lacks rough endoplasmic reticulum. The neurotubules and neurofilaments are gathered into small parallel bundles, connected by electron-dense cross-bridges. Here at the initial segment, the axolemma (the plasma membrane bounding the axon) is lined by a dense core consisting of spectrin and F-actin, allowing voltage sensitive channels to attach to the plasmalemma. Each myelin segment is separated from the neighboring node along the length of the axon by nodes of Ranvier. These nodes, where axonal branches arise, contain sodium and possibly potassium channels. Axonal terminals are initially myelinated, but as they repeatedly branch, myelin sheaths will disappear. This will enable terminals to establish synaptic contacts with axons, dendrites, neurons in the CNS, or muscle fibers and glands in the PNS. The endings are characterized by tiny swellings known as terminal boutons. Microtubule-associated proteins (MAP), such as tau, interconnect axonal microtubules. Within the axon microtubules, neurofilaments, lysosomes, and mitochondria are located. Microtubules have polar ends (+ and −) with the + ends directed away from the perikaryon. They contain kinesin-coated organelles and are where axonal growth occurs. Dynesin-coated organelles are located on the (−) ends. Kinesin and dynesin bind to membrane receptors.

Neurofilaments are usually found in association with microtubules as constant components of axons. In the growth cones of the developing axons, filamentous structures finer than neurofilaments exist, known as microfilaments. These actin filamentous structures facilitate growth and movement and can be inhibited by chemical agents that depolymerize actin. Neurofilaments within the regenerating axons contain a calmodulin-binding membrane-associated phosphoprotein and growth-associated protein-43 (GAP-43), which may be used as markers to identify these axons.

Proteins, neurotransmitters, mitochondria, and other cellular structures synthesized in the soma or proximal portion of the dendrites are transported to the axon and axon terminals via a process known as axoplasmic transport. This transport may occur in a distal (anterograde) direction toward the axon terminals, while allowing other substances to be transported in the reverse (retrograde) direction from the axon toward the cell body. Axoplasmic transport within the microtubules may be maintained utilizing protein dynein and kinesin. This process may involve fast, intermediate, and slow phases.

The fast phase of axoplasmic transport includes the transport of selected proteins (e.g., molecules carried by the hypothalamo-hypophyseal tract), vesicles, membrane lipids, or enzymes that act on transmitters. This phase of the transport occurs at a speed of 100–400 mm/day, in both anterograde and retrograde directions, utilizing the smooth endoplasmic reticulum and microtubules. The retrograde component of this phase is formed by the degraded structures within the lysosomes and may contain neurotropic viruses such as rabies and herpes simplex. The fast phase is energy-dependent and can be inhibited by colchicine, hypoxia, and the inhibitors of oxidative phosphorylation, glycolysis, and the citric acid cycle. It has been suggested that proteins that follow the fast axonal transport must either pass through the Golgi complex or join proteins that do so, utilizing the clathrin-coated vesicular protein. The activation of kinesin or dynesin can determine the direction of the fast phase of transport. In the intermediate phase mitochondrial proteins are transmitted at a rate ranging between 15 and 50 mm/day. The slow phase of the transport utilizes microtubules and microfilaments as well as neurofilament proteins, mitochondria, lysosomes, and vesicles, proceeding in the anterograde direction only, at a speed of 0.1–3 mm/day. This phase carries 80% of the substances carried by axoplasmic transport, providing nutrients to the regenerating and mature neurons. The slowest phase deals with the transportation of triplet proteins of tubulin and neurofilaments.

An axon may be myelinated or unmyelinated and ends in the synaptic terminals. Myelinated axons have a faster conduction velocity of the impulses generated. Myelin is formed by the Schwann cells in the PNS and by the oligodendrocytes in the CNS. This is an insulating complex cover of cell membranes with a unique ultrastructural form that encircles axons and is composed of two-thirds lipid and one-third protein.

Myelin allows for substances to be transported between the axon and the myelin forming cells (Schwann cells or oligodendrocytes). It maintains high-velocity saltatory nerve conduction, a mode of conduction that proceeds from one node of Ranvier to another in a faster and more energy-efficient way. Myelin is not a continuous covering but rather a series of segments interrupted by nodes of Ranvier. In the PNS, each internodal segment represents the territory of one Schwann cell. These nodes are sites of axonal collaterals and bare areas for ion transfer to and from the extracellular space. Extensions of the myelin on both sides of a node of Ranvier are known as paranodal bulbs. These myelin bulbs may lose contact with the axon and undergo degeneration as a result of a crush injury. Interruptions within successive layers of myelin are known as Schmidt–Lanterman incisures. Myelin is formed by the oligodendrocytes or Schwann cells during the fourth month of fetal life and continues into postnatal life.

Myelination is initiated near the soma of neurons and continues toward the axon terminals. It does not cover the axon hillock, dendrites, or axonal terminals. For the myelination process to begin and be maintained, adhesion/recognition molecules, such as MAG and P0, must come to action. It is partly determined by the diameter of the axon and occurs in axons that range between 1.5 μm in the PNS to 1 μm in the CNS.

The first step of this process involves surrounding the axon by cytoplasmic membranes of Schwann cells or oligodendrocytes that are detached initially but later fuse together. The double layer of the Schwann cell plasma membrane wraps the axons and forms the meson, which elongates and differentiates into inner and outer parts. It has been suggested that myelination involves the deposition of P0, MAG, and PLP into the lamellae after their transportation as vesicles to the membrane protein at the mesoaxon and also the incorporation of soluble proteins such as MBP at the paranodal regions.

In the process of myelination, several layers of cell membranes surround a given axon in a tight spiral manner, separated by the cytoplasm. The presence of actin and tubulin at the paranodal region and the Schmidt-Lanterman incisures and their contractile effect may play a role in the coiled arrangement of the myelin. Since myelin formation occurs at a particular site, elongation of the axon requires successive layers of myelin to stretch and cover a larger area of the axon. This results in more layers being concentrated near the center of the internode. When the cytoplasmic and external surfaces of cell membranes come into apposition upon receding of the cytoplasm, they form continuous major and minor dense lines, respectively. The minor dense line, also known as the intraperiod line, contains a gap that allows extracellular space to continue with the periaxonal space. This intraperiod gap allows for metabolic exchange and serves to accommodate the increasing thickness of the axon by permitting lamellae to slip on one another and thus reduce their numbers. The thickness of myelin is paralleled to an extent by an increase in the diameter of the axon. Myelination is a sporadic process that does not follow a uniform pattern in early postnatal and late fetal life.

In contrast, oligodendrocytes, the myelin-forming cells in the CNS, are associated with more than one axon and with more than one internodal segment (roughly 15–50 internodes). Unlike that of the PNS, the elongation of an axon to an intended site precedes the movement of the originators of the oligondendrocytes. Thus, axonal contact, up-regulation of transcription of myelin protein genes, elevation of cAMP, and down-regulation of suppressor genes appear to be interrelated, essential work in cohort in the myelination process of PNS axons. This issue of axonal contact is of no value in the myelination process of the CNS axons as axonal activity seems to play a more significant role in the proliferation and survival of the oligodendrocytes.

Thus, the multiple associations are maintained by extension of the oligodendrocytes around each axon. Myelination in the CNS begins with the vestibular and spinocerebellar tracts. Corticospinal tract and dorsal white column pathways may not be completely myelinated at birth. It should also be remembered that axonal growth and elongation to a destination generally occur before the migration of oligodendrocytes and formation of myelin. Myelination is a vital element in fast action potential and is considered to be a significant index that signals the degree of maturity of neural pathways. There exists a degree of variability regarding the myelination process. T1 and T2 weighted magnetic resonance images (MRIs) enable visualization of the gray matter as well as the white matter, which consists of myelinated axons [18]. The extent of myelination increases with age, particularly between birth and the second decade of life [19]. This distinct increase in the white matter, which is accompanied by a decrease in the cortical gray matter, is attributed to the ongoing myelination process [18].

The degree of myelination can be detected through an MRI in the pons and the cerebellar peduncle at birth while in the posterior limb of the internal capsule, optic radiation, and the adjacent part of the corpus callosum (splenium). The myelination becomes visible by the fourth month of postnatal life. The anterior limb of the internal capsule and the genu of the corpus callosum show myelination 6 months after birth, while the myelination process of the white matter of the frontal, parietal, and occipital lobe may take up to one year. Early signs of myelination in the corpus callosum appear in the splenium at and around 4 months of postnatal life and in the geu at the middle of the first year of postnatal life [19]. The myelination process of the corpus callosum is finalized by 8 months of postnatal growth. Despite this fact, a disproportionate increase in the size of the corpus callosum continues until 18 months of age, particularly in the splenium, with no detectable changes in the genus [20]. Since the commissural fibers in the splenium of the corpus callosum connect identical areas in the temporo-occipital cortex, a perceptible growth in this cortex explains the distinct increase in the size of the splenium with age [18]. The extent of myelination of the left frontotemporal white matter appears to be greater than that of the right hemisphere, which accounts for the maturation of the myelination of the pathways associated with Broca's and Wernicke's centers of the dominant hemisphere [18]. Studies of Thompson et al. based on longitudinal MRIs ascertained a rostrocaudal growth in the development of the corpus callosum, which indicates the direction of the myelination process [21]. Commissural fibers of the corpus callosum that connect identical areas in the frontal lobe white matter show the fastest growth between the third and sixth years of life, whereas the commissural fibers that interconnect the temporoparietal cortices within the isthmus of the corpus callosum show extensive and sustained myelination and thus profound growth rates between the sixth and fifteenth years of age. While certain regions of the brain, such as the occipital lobe, motor, and somatosensory cortices, remain constant, others, such as the prefrontal and temporoparietal regions, exhibit noticeable growth between the seventh and thirteenth years of age. These areas, which regulate language, display a decline in growth proportional to the decline in language capabilities by the age of 15 years, exemplified in the relative slow learning of a language passed the age of 12 years [22].

Unmyelinated axons in the CNS lack any form of ensheathment, whereas unmyelinated axons of the PNS are enveloped by Schwann cell cytoplasm. Peripheral axons are lodged in sulci along the surface of Schwann cells. Some Schwann cells in the PNS may encase more than 20 axons through the multiple grooves on their surfaces.

Demyelination may be a primary or secondary process. Primary demyelination affects the thickly myelinated motor fibers and is associated with intact axons, as in multiple sclerosis and myelinopathy, which affects the thickly myelinated motor fibers of the lower extremity and spares the small sensory fibers. Demyelination secondary to destruction of the axon may be seen in storage diseases and Wallerian degeneration. Incomplete myelination (hypomyelination) occurs in maple syrup urine disease and in phenylketonuria.

Contrary to the established belief that the CNS is a passive entity that lacks the capacity to rejuvenate following axonal injury, it is now evident that in order to restore neuronal function, new synapses, though irregular and less efficient, come to existence following a traumatic experience. It has been shown that these new synaptic connections are formed by other afferents to the denervated site. In order to expand the CNS' capability to recover from traumatic impact, embryonic neuronal transplant has been introduced.

Studies conducted on neuronal transplantation have demonstrated that embryonic tissue with similar characteristics to the affected neurons or genetically modified tissue can establish synaptic linkage with the damaged host neurons. Replacement of the degenerated dopamine-secreting nigral neurons with similar tissue of embryonic origin has had variable success. Axonal interruption in the CNS causes the loss of capacity to regenerate except when a peripheral nerve segment is transplanted to guide and bridge the gap between severed segments of the axon for a limited regenerative process. In this process, the transplanted astrocytes and Schwann glial cells enter and follow the fiber tract of the affected axons. The role of the perivascular microglia is in expressing MHCI and II antigen and secreting cytokines that in turn induce luminal adhesion molecules of the lymphocytes and graft cells to express MHCI antigens. Further stimulation of the perivascular microglia is provided by diapedetic lymphocytes through the lymphocyte factor such as gamma interferon (IFNγ).

This feedback activation perpetuates the activation process to involve the entire transplanted tissue and is eventually followed by the introduction of MHC II (major histocompatibility complex), LFA-I (leukocyte function-associated antigen-1), and CD4 cluster designation-4 that express dendritic cells in the perivascular space. Despite all the accumulated data from experiments, there remains a much greater challenge in the ability to pattern the embryonic axonal development with that of the adult, which appears to be significantly different with regard to patterning, direction, and the presence of certain contiguous glial cells. Further, the CNS immune response to transplanted embryonic tissue is not fully understood, and the apprehension remains that a major degenerative disease may ensue as a result of the introduction of an antigen through the transplanted tissue.

Neurons are classified according to the chemical nature of the neurotransmitter that they release into cholinergic, adrenergic, noradrenergic, dopaminergic, serotoninergic, GABAergic neurons, etc. Cholinergic neurons release acetylcholine and are commonly found at neuromuscular junctions. Noradrenergic neurons are abundant in the sympathetic ganglia and the reticular formation, whereas adrenergic neurons are found in the adrenal medulla and within the synaptic dense cored vesicles. Dopaminergic neurons are present mainly in the substantia nigra, corpus striatum, and cerebral cortex, while serotoninergic neurons occur in the raphe nuclei and in the rounded synaptic vesicles. GABAergic neurons are present in the cerebellar cortex and spinal cord. Neurons may also be classified into pseudounipolar, bipolar, and multipolar neurons.

Unipolar neurons are the simplest class of neurons that exhibit a single extension that gives rise to branches, some of which are receptive (dendrites); others function as axons. True unipolar neurons, which are relatively rare in vertebrates, form the dorsal root ganglia, the granule cells of the olfactory system, and the mesencephalic trigeminal nucleus. Pseudounipolar neurons give off a single process that divides into a peripheral receptive branch (dendrite) and a central extension serving as an axon. Both of these branches maintain a structural resemblance to axons.

Bipolar neurons are also a relatively uncommon class of neurons. They are symmetrical cells with an ovoid or elongated body, a single dendritic process, and an axon arising from opposite poles. These processes are approximately equal in length. They form the vestibular (Scarpa's) ganglia, spiral (auditory) ganglia, and the retinal bipolar cells.

Multipolar neurons are the most common types of neurons in the CNS; they form the autonomic ganglia. They possess a single axon with several symmetrically radiating dendrites. Some neurons have multiple axons or lack axons all together. Multipolar neurons can be classified on the basis of their dendritic branching pattern and shape of the soma into stellate, pyramidal, fusiform, Purkinje, and glomerular cells.

Stellate (star) cells are found in the spinal cord, reticular formation, and cerebral cortex. They have dendrites of equal lengths (isodendritic) that radiate uniformly in all directions.

Pyramidal cells are multipolar, exhibiting pyramidal-shaped soma with basal dendrites and a single apical dendrite that ascends toward the surface of the cerebellar cortex. They are most abundant in the cerebral cortex and hippocampal gyrus.

Fusiform cells are distinguished by their spindle-shaped and flattened soma with dendrites at both ends.

Purkinje cells that form the intermediate layer of the cerebellar cortex have flask-shaped soma with apical tree-like dendritic branches, ascending toward the surface of the cerebellum and maximizing synaptic contacts. Purkinje cells are motor neurons that project long axons beyond the area of the soma.

Glomerular cells have a few convoluted dendritic branches and form the mitral and tufted cells of the olfactory bulb. Mitral cells have an inverted cone-shaped dendritic field and soma that resembles a bishop's miter.

Anaxonic cells are abundant in the retina (amacrine cells) and the olfactory bulb, where they are known as granule cells.

On the basis of axonal length, multipolar neurons can also be categorized into Golgi type I, with long axons projecting to distant parts of the CNS, and Golgi type II, possessing short axons that establish contacts with local neighboring neurons. The Golgi type II represents the inhibitory interneurons (such as the periglomular olfactory neurons), which are activated by the ascending sensory pathways and play an important role in lateral inhibition. Neurons without axons, as mentioned earlier, are known as anaxonic, such as the amacrine cells of the retina and granule cells of the olfactory bulb, which establish synapses with parallel neurons.

Neurons can also be classified based on their functional role into somatic motor, somatic sensory, visceral motor, and visceral sensory neurons.

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Visceral Motor Pathways

T.B. Jones, J.A. Kaufman, in Fundamental Neuroscience for Basic and Clinical Applications (Fifth Edition), 2018

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Cellular Components of Nervous Tissue

Patrick R. Hof, ... Bruce D. Trapp, in From Molecules to Networks (Third Edition), 2014

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Hypothalamic Supraoptic and Paraventricular Nuclei

William E. Armstrong, in The Rat Nervous System (Third Edition), 2004

Supraoptic Interneurons

A very small number of multipolar neurons with small somata are found within the SO and could function as interneurons (Dyball and Kemplay, 1982; Bruni and Perumal, 1984). An additional locus of interneurons is the perinuclear zone (PZ) immediately adjacent to the SO (Figs. 2A and 5). Many neurons in the PZ project to the SO (Iijima and Ogawa, 1981; Tribollet et al., 1985; Jhamandas et al., 1989; Roland and Sawchenko, 1993; Levine et al., 1994), and this zone is a target of many inputs known to influence the firing rate of OX and VP neurons. Thellier et al. (1994) place the densest population of locally projecting PZ neurons to a medial region dorsal to the optic chiasm rather than immediately dorsal to the SO. PZ neurons are morphologically diverse (Armstrong and Stern, 1997) and can express many neuroactive substances including GAD or GABA (Tappaz et al., 1983; Theodosis et al., 1986; Okamura et al., 1990), choline acetyltransferase (Mason et al., 1983), substance P (Larsen, 1992), somatostatin (Mezey et al., 1991), estrogen receptor (Herbison et al., 1994), pituitary adenylate cyclase-activating polypeptide (PACAP) (Hannibal et al., 1995) and probably glutamate (Boudaba et al., 1997). All of these substances have been identified in fibers and some even in synaptic terminals within the SO. Much of the somatostatinergic input to the SO derives from the PZ (Mezey et al., 1991). PZ neurons are electrophysiologically distinct from SO neurons (Armstrong and Stern, 1997) and contribute functional inhibitory (Wuarin, 1997) and excitatory synapses (Boudaba et al., 1997) to the nucleus. The GABAergic neurons are thought to be important in mediating the response of AVP neurons to hypertension (Nissen et al., 1993; Grindstaff and Cunningham, 2001).

FIGURE 5. Photomontage of a PZ neuron filled with Neurobiotin and reacted with avidin–biotin peroxidase complex. A short axon from this neuron displays terminal-like varicosities in close proximity to SO neurons stained with thionine.

Modified from Armstrong and Stern (1997).

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Hypothalamic Supraoptic and Paraventricular Nuclei

William E. Armstrong, in The Rat Nervous System (Fourth Edition), 2015