Nervous Tissue

Nervous tissue is the main tissue of the nervous system, functioning to communicate sensory information throughout the body via action potentials.

There are two parts of the nervous system; the central nervous system (CNS) consisting of the brain and spinal cord, and the peripheral nervous system (PNS) which includes nervous cells located outside of the CNS. Within this, only two cell types make up nervous tissue alongside the ECM. **Neurons** are the highly specialised excitable cells that usually come to mind when thinking about the nervous system. Their general structure includes the cell body (or perikaryon) in which the [usual/ expected] cytoplasmic elements are contained, dendrites that receive signals conducted towards the cell body, and a single axon carrying action potentials away from the cell body towards pre-synaptic terminals. This directional flow is facilitated by the cell’s high polarity. A common feature to neurons is the myelin sheath which insulates the axon and allows rapid impulse induction by nodes of Ranvier. The three main types of neuron include sensory neurons which convert stimulus to action potentials to send to the CNS, motor neurons (which signal to muscle or gland to giving an output) and interneurons (connect sensory and motor through the CNS) each varying slightly in structure. **Neuroglial** cells are the electrically inactive part of nervous tissue also lacking axons and dendrites, they are much smaller than neurons but function in supporting them through several methods depending on the type and location.

**Communication in nervous tissue**

Within neurons, communication is based on signal transduction as a result of potentials between the outside and inside of the cell. Certain stimuli (such as changes in membrane potential, presence of a neurotransmitter or mechanical stimulation) causes a change in ion channels that resulting in the redistribution of ions, and in turn (with depolarisation reaching a certain threshold) action potentials travel down the neuron. Chemical synapses allow chemical communication between neurons. Depolarisation of the presynaptic terminal causes Ca2+ influx which triggers release of a neurotransmitter into the synapse. The neurotransmitter moves down a concentration gradient where it is received by post-synaptic receptors of the dendrite terminal. Gap junctions also allow for communication between adjacent neurons; often named electrical synapses, these allow passing of signals between neurons faster than chemical synapses and are most often found in the CNS [5]. There are many methods of communication between neurons and glial cells. This includes ion fluxes, neurotransmitters, cell adhesion molecules and chemical signalling from non-synaptic regions of the neuron. Ca2+ fluxes are involved in communicating when signals are being transduced in neurons to glial cells such as astrocytes[6]. Gap junctions between neurons and glial cells are relatively large, transmitting not only ionic currents but allowing the passage of secondary messengers such as cAMP. Gap junctions between glial cells are also present to signal each other- a range of compounds are signalled including ATP, IP3 and Ca2+.

**Formation of nervous tissue**

Nervous tissue develops from the ectoderm germ layer in embryonic development; the neural plate develops from this, serving as the foundation structure from which the neural tube and crest are formed during neurulation. These structures initially contain stem cells and progenitor cells (an intermediate between stem cells and differentiated cells) which proliferate and only undergo mitosis before differentiation. This is because neuronal cells are unable to undergo mitosis, [in fact we have the same neurons our whole life]. This step also allows positioning of cells such as radial progenitor cells (RPC) in preparation for later developmental processes. The neural tube gives rise to components of the CNS; the neuroepithelium initially contains stem cells which eventually give rise to neuronal and glial cells [7], whereas the neural crest gives rise to a large number of cell types including those of the PNS. Migration of neural crest cells through somatic cell populations is what results in formation of PNS neuronal and glial cells after differentiation [7]. These processes are directed by chemical secretions from the mesoderm. Neuronal migration ensures the correct positioning of differentiated neurons within the nervous system after the final round of mitosis. This involves three distinct phases of movement where the differentiated neuron moves along a RPC; first the leading process is extended, followed by movement of the cell body, and finally retraction of the tail process [8]. The RPCs act as a road over which neurons move along using adherens junctions, particularly n-cadherin which is recycled as the neuron moves forward. Once the neuron has migrated and sits in the correct location it is then orientated into proper position. With additional layers of nerve cells in the CNS, the later produced cells migrate past earlier cells creating layers where youngest neurons sit above older neurons.

**Extracellular matrix of Nervous tissue**

Excreted by several cell types, the extracellular matrix is an important factor in explaining how cells form nervous tissue. It maintains structure by providing physical support through anchorage and aiding organisation, whilst chemically, it provides a source of molecules that guide growth and development.

The ECM of the PNS is produced primarily by Schwann cells but neurons can also influence its formation. These create a basal lamina which in nervous tissue is a thin sheet surrounding axons and the Schwann cells themselves. External to the basal lamina lies a second component of nervous ECM named the fibrillar matrix. The Schwann cell extracellular matrix is comprised of many ECM molecules such as glycoproteins, collagens, laminin and proteoglycans which interact with nervous tissue cells through integrin (and non-integrin) cell receptors [9], a more in depth review of all schwann cell ECM components can be found here. In the brain there are three ECM components; the basal lamina, perineuronal nets, and the neuronal interstitial matrix which together occupy 10-20% of the brains volume[10]. Of these, perineuronal nets are the component secreted by nerve tissue cells; comprised predominantly of proteoglycans, link proteins and tenacin R, it surrounds the cell body and dendrites of CNS neurons[10].

In development, the adhesion and chemical properties of the ECM guide proliferation and growth, establishing connections between neurons, informing directional growth and forming synapses. For example, in neuronal migration, endfeet of RPCs are attached to basal lamina laminin and perlcan via intergrin and dystroglycan receptors [11]. Furthermore, expression of laminin subunits are integral in signalling during migration and differentiation of neuronal stem cells. Connections formed in development also can be maintained throughout life such as in the formation of synapses [11] and formation of connections at a neuromuscular junction.

Sources and extra reading:

[1]Knapp S. 2020, *Glial Cells*, Available at: https://biologydictionary.net/glial-cells/ [accessed 09/03/22]

[2] Hof P.R, Kidd G, DeFilipe J, Vellis J, Sosa A.G, Elder G.A, Trapp B.D, 2013, Cellular Components of Nervous Tissue, Fundamental Neuroscience Fourth Edition Pages 41-59, doi: https://doi.org/10.1016/B978-0-12-385870-2.00003-2

[3] Purves D, Augustine GJ, Fitzpatrick D, et al., 2001, Neuroglial Cells, *Neuroscience*. 2nd edition. Sunderland (MA): Sinauer Associates.

[4] Söhl, G., Maxeiner, S. & Willecke, K. 2006 Expression and functions of neuronal gap junctions. *Nat Rev Neurosci 6*, 191–200 Doi: https://doi.org/10.1038/nrn1627

[5] Fields, R. D., & Stevens-Graham, B. (2002). New insights into neuron-glia communication. *Science*, 298(5593), 556–562 Doi: https://doi.org/10.1126/science.298.5593.556

[6] de Vellis J, Carpenter E. 1999, General Development of the Nervous System, *Cellular and Medical Aspects.* 6th edition

[7] Y.-H. Youn, A. Wynshaw-Boris. 2009, Nuclear Movements in Neurons, *Encyclopedia of Neuroscience* Pages 1277-1281, Doi: https://doi.org/10.1016/B978-008045046-9.00727-0.

[8] Lau L. *et al* 2013, athophysiology of the brain extracellular matrix: a new target for remyelination. *Nat Rev Neurosci* 14, 722–729 Doi: https://doi.org/10.1038/nrn3550

[9]Chernousov M.A, Carey D.J, 2000, Schwann cell extracellular matrix molecules and their receptors, *Histol Histopathol* 15: 593-601 Doi: 10.14670/HH-15.593

[10] Barros C.S, Franco S.J, Muller U, 2011, Extracellular Matrix: Functions in the Nervous System, Cold Spring Harb Perspect Biol; 3:a005108 Doi: 10.1101/cshperspect.a005108

[11]ScientistCindy.com, Nervous Tissue, Available at:https://www.scientistcindy.com/nervous-tissue.html [accessed 20/02/22]