Neurons and their properties

 

  • Neurons/glia 

A neuron is a cell with two characteristic properties: electrical excitability and conductivity. Neurons have many functions that divided them into three main types: (1) primary sensory neurons, (2) motor neurons and (3) interneurons. Sensory neurons sense changes in the environment and communicate these changes to other neurons in the central nervous system (CNS). According to this information, the body knows how to response to the stimuli. Motor neurons, on the other hand, receive input from the CNS on how to control the body, including body functions such as muscle movement and gland function. Interneurons are neurons that connect with other neurons. They are the central nodes of neural circuit, enabling communication between sensory or motor neurons with the CNS. They play vital roles for instance in reflexes, neuronal oscillations and neurogenesis.

Neurons are in many ways like “normal” cells. They have nuclei that contains all the genetic information, mitochondria that powers the cell in addition to smooth/rough ER and Golgi apparatus all of which are involved in protein synthesis and/or post-translational processing of the proteins. What differentiates neurons from other cells is their characteristic thread-like shape provided by the cytoskeleton in addition to the neurites connected to the soma i.e. the cell body. Neurites include axons and dendrites. Axons are long projections of the neuron that conduct electrical impulses known as action potentials away from the soma. The axon’s end site is called axon terminal in which the axon comes in contact with other cells and passes information to them via synapse. Dendrites, on the other hand, receive information via synapses from other neural cells and propagate it to the soma. Neurons have usually numerous dendritic branches that form a collective structure called dendritic tree. 

Glial cells, consisting of microglia, astrocytes, and oligodendrocyte lineage cells as their major components are non-neuronal cells in the CNS and PNS that are not electrically excitable. They have four main functions: (1) to surround and support neurons, (2) to supply nutrients and oxygen to neurons, (3) to insulate neurons and (4) to destroy pathogens and remove dead neurons. Most abundant glial cells are astrocytes which fill most of the space between neurons. They regulate the chemical content in the extracellular space and envelop synaptic junctions prohibiting the leaking of neurotransmitters beyond synaptic cleft. Myelinating glia provide layers of membrane to insulate axons which increases the propagation speed of action potentials, thus enabling the fast flow of information in the body. There are two types of myelinating glia: oligodendroglial in the CNS providing myelin to several axons and Schwann cells in the PNS providing myelin to only a single axon. Microglial cells are phagocytes that remove debris left by dead or regenerated cells.

Glia were originally considered as purely non-functional glue for neurons but by ablating single glial cell populations, researchers have confirmed their importance as well as further discovered the functions of glial cells. The literature shows that astrocyte ablations cause negative effects on overall neuronal survival in the cerebellum and in the spinal cord. Astrocyte ablation in cervical spinal cord in mice showed axonal degeneration in addition to paralysis of all limbs caused by the failure to buffer reactive oxygen and nitrogen species. (Schreiner et al., 2015) This indicates that one of the important functions of the astrocytes truly is the regulation of chemical content in the extracellular space by for instance buffering these substances that are damaging to the nervous system. By ablating a microglial cell population on mice, Parkhurst et al. found a loss of motor-dependent synapse formation and a decreased performance in learning tasks (Parkhurst et al., 2013). Additionally, a loss of about 80% of hippocampal microglia resulted in alteration in social behaviour in mice (Torres et al., 2016). These results indicate that the phagocytic properties of microglia are essential in maintaining brain homeostasis. The function of oligodendrocytes is clear as they are the myelin-producing cells that insulate axons allowing fast propagation of action potentials. However, the function of non-myelinating oligodendrocytes present in sparsely myelinated brain regions like the gray matter in the cerebral cortex is a bit more unclear. Studies however show that non-myelinating oligodendrocytes for instance carry transcripts for all major myelin proteins (Paez et al., 2009) and may thus be able to remyelinate denuded axons after injury (Gregersen et al., 2001).

 

  • Neuronal membrane at rest

 

The membrane potential is analogous to a capacitor that is waiting to discharge. The cell membrane has  a resting electrical potential of approximately -70mV. This potential difference arises due to the differences of ion concentrations inside and outside of the cell. The main ions that dictate this potential are sodium and potassium, but also include other ions like chloride and calcium. When the cell membrane is at rest, potassium ions move from inside to outside the cell due to diffusion through leaky potassium ion channels. The leaky potassium ion channel does not allow sodium into the cell because the residues of the channel are selective of ion size with a solvent shell. Only a few potassium ions are required to move to the other side of the membrane to create a potential difference. The net flux of potassium across the membrane stops when the electromotive force pushing potassium into the cell equals the diffusive force pushing potassium out of the cell. The potassium ions that leak to the outside hang around the membrane, leaving negative charge behind on the inside of the cell membrane. 

The amount of ions needed to create the potential difference is really small. It should also be noted that the extracellular fluid and intracellular fluid are net neutral, so only the membrane locally contains this electrical potential. If the difference in ion concentrations between inside and outside of the cell create an electrochemical gradient that charges the membrane capacitor, how is this gradient created in the first place? Creating an electrochemical gradient seems to go against entropy and must require energy. The sodium potassium pump is the key to creating the ion concentration gradients with a little help from its friend ATP.

         The sodium potassium pump pushes a high concentration of potassium inside the cell and sodium outside the cell. The majority of a neurons’ ATP goes to maintaining the ion concentrations. 

We have also looked into circuit models of the neuron membrane. The neuron membrane can be modeled by a battery (representing the potential difference set by the sodium potassium pump and leaky potassium channels) in parallel with capacitors and resistors. The capacitors represent the membrane holding charge. The resistors have conductance values representing ion channels in the membrane. A high conductance means that ions easily flow through that channel, like the leaky potassium channels. A low conductance means that ions struggle to move across the membrane. However, some of these resistors have varying resistances. For example, the voltage gated sodium channel increases in conductance during an action potential, which is the next topic of this super awesome blog.

 

  • Action potential

 

As mentioned before, neurons are electrically excitable. They send messages to one another through a chain of  electrical signals until they reach the cerebral cortex area of the brain, which is the part of the brain that interprets sensations. An action potential is a signal that propagates from the axon of one neuron to the dendrites of another. 

A graded potential is created in a sensory receptor, specifically a mechanoreceptor. A graded potential is a change in the membrane potential.  The mechanical stimulant is converted to an electrical one, which is then interpreted by the receptor. As a result, gated ion channels in the nerve endings open, which causes ions to flow in , changing the potential inside the cell membrane. Membranes have a resting potential of about -70V. An action potential acts in an “all or nothing” way, meaning it has to get to a certain threshold in order to continue. When the potential of a cell is under the threshold, the voltage-gated channels are shut, but when it gets to threshold, the channels to open and positive sodium ions flow in from the extracellular fluid. This causes the cell membrane to depolarize. The ions move according to their electrical gradient. After the neuron membrane has completely depolarized, the cell reverses this action by opening voltage-induced potassium channels. Potassium ions flow out of the cell. After a short time, the resting membrane is recovered. At the same time, the action potential travels along the axon until it causes a neurotransmitter to be released. A neurotransmitter is a chemical signal that is released at the axon terminal to the synapse of another neuron. They are transported in synaptic vesicles to the synapses (connections) located at the ends of the dendrites of the other neuron. The neurotransmitter released to the dendrites of the interneuron triggers a change in potential in the next neuron. After this potential travels through the axon due to the movement of ions, another neurotransmitter is released at the synapse of another interneuron. The same chain is repeated until some kind of effect happens, such as a muscle contracting or feeling pain. 

References

Bear, Mark F., et al. Neuroscience: Exploring the Brain. 4th ed., Jones & Bartlett Learning, 2016. 

Gregersen R, Christensen T, Lehrmann E, Diemer NH, Finsen B. Focal cerebral ischemia induces increased myelin basic protein and growth-associated protein-43 gene transcription in peri-infarct areas in the rat brain. Experimental Brain Research. Vol. 138, 2001, pp. 384-392. Available (accessed on 18.9.2020): doi:10.1007/s002210100715

Paez P, Fulton D, Spreuer V, Handley V, Campagnoni C, Macklin W, et al. Golli myelin basic proteins regulate oligodendroglial progenitor cell migration through voltage-gated Ca2+ influx. The Journal of Neuroscience. Vol. 29, 2009, pp. 6663–6676. Available (accessed on 18.9.2020):  https://doi.org/10.1523/JNEUROSCI

Parkhurst N, Yang G, Ninan I, Savas N, Yates R, Lafaille J, et al. Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor. Cell. Vol. 155, 2013, pp. 1596–1609. doi: https://doi.org/10.1016/j.cell.2013.11.030

Schreiner B, Romanelli E, Liberski P, Ingold-Heppner B, Sobottka-Brillout B, Hartwig T, et al. Astrocyte depletion impairs redox homeostasis and triggers neuronal loss in the adult CNS. Cell Reports. Vol. 12, 2015, pp. 1377–1384. Available (accessed on 18.9.2020): https://doi.org/10.1002/glia.23055

Torres L, Danver J, Ji K, Miyauchi J, Chen D, Anderson M, et al. Dynamic microglial modulation of spatial learning and social behavior. Brain, Behaviour, and Immunity. Vol. 55, 2016, pp. 6–16. Available (accessed on 18.9.2020): https://doi.org/10.1016/j.bbi.2015.09.001

Tortora, Gerard J. Principles of Anatomy and Physiology. John Wiley & Sons Australia, Ltd, 2019.

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