Cellular neuroscience



Cellular neuroscience is the study of neurons at a cellular level. This includes morphology and physiological properties of single neurons. Several techniques such as intracellular recording, patch-clamp, and voltage-clamp technique, pharmacology, confocal imaging, molecular biology, two photon laser scanning microscopy and Ca2+ imaging have been used to study activity at the cellular level. Cellular neuroscience examines the various types of neurons, the functions of different neurons, the influence of neurons upon each other, how neurons work together.

Neurons are cells that are specialized to receive, propagate, and transmit electrochemical impulses. In the human brain alone, there are over eighty billion neurons. Neurons are diverse with respect to morphology and function. Thus, not all neurons correspond to the stereotypical motor neuron with dendrites and myelinated axons that conduct action potentials. Some neurons such as photoreceptor cells, for example, do not have myelinated axons that conduct action potentials. Other unipolar neurons found in invertebrates do not even have distinguishing processes such as dendrites. Moreover, the distinctions based on function between neurons and other cells such as cardiac and muscle cells are not helpful. Thus, the fundamental difference between a neuron and a nonneuronal cell is a matter of degree.

The Hodgkin–Huxley model of an action potential in the squid giant axon has been the basis for much of the current understanding of the ionic bases of action potentials. Briefly, the model states that the generation of an action potential is determined by two ions: Na+ and K+. An action potential can be divided into several sequential phases: threshold, rising phase, falling phase, undershoot phase, and recovery. Following several local graded depolarizations of the membrane potential, the threshold of excitation is reached, voltage-gated sodium channels are activated, which leads to an influx of Na+ ions. As Na+ ions enter the cell, the membrane potential is further depolarized, and more voltage-gated sodium channels are activated. Such a process is also known as a positive feedback loop. As the rising phase reaches its peak, voltage-gated Na+ channels are inactivated whereas voltage-gated K+ channels are activated, resulting in a net outward movement of K+ ions, which repolarizes the membrane potential towards the resting membrane potential. Repolarization of the membrane potential continues, resulting in an undershoot phase or absolute refractory period. The undershoot phase occurs because unlike voltage-gated sodium channels, voltage-gated potassium channels inactivate much more slowly. Nevertheless, as more voltage-gated K+ channels become inactivated, the membrane potential recovers to its normal resting steady state..

After neurotransmitters are synthesized, they are packaged and stored in vesicles. These vesicles are pooled together in terminal boutons of the presynaptic neuron. When there is a change in voltage in the terminal bouton, voltage-gated calcium channels embedded in the membranes of these boutons become activated. These allow Ca2+ ions to diffuse through these channels and bind with synaptic vesicles within the terminal boutons. Once bounded with Ca2+, the vesicles dock and fuse with the presynaptic membrane, and release neurotransmitters into the synaptic cleft by a process known as exocytosis. The neurotransmitters then diffuse across the synaptic cleft and bind to postsynaptic receptors embedded on the postsynaptic membrane of another neuron. There are two families of receptors: ionotropic and metabotropic receptors. Ionotropic receptors are a combination of a receptor and an ion channel. When ionotropic receptors are activated, certain ion species such as Na+ to enter the postsynaptic neuron, which depolarizes the postsynaptic membrane. If more of the same type of postsynaptic receptors are activated, then more Na+ will enter the postsynaptic membrane and depolarize cell. Metabotropic receptors on the other hand activate second messenger cascade systems that result in the opening of ion channel located some place else on the same postsynaptic membrane. Although slower than ionotropic receptors that function as on-and-off switches, metabotropic receptors have the advantage of changing the cell's responsiveness to ions and other metabolites, examples being gamma amino-butyric acid (inhibitory transmitter), glutamic acid (excitatory transmitter), dopamine, norepinephrine, epinephrine, melanin, serotonin, melatonin, and substance P.

In neuroscience, synaptic plasticity is the ability of synapses to strengthen or weaken over time, in response to increases or decreases in their activity.

Since memories are postulated to be represented by vastly interconnected networks of synapses in the brain, synaptic plasticity is one of the important neurochemical foundations of learning and memory (see Hebbian theory).

Plastic change often results from the alteration of the number of neurotransmitter receptors located on a synapse. There are several underlying mechanisms that cooperate to achieve synaptic plasticity, including changes in the quantity of neurotransmitters released into a synapse and changes in how effectively cells respond to those neurotransmitters. Synaptic plasticity in both excitatory and inhibitory synapses has been found to be dependent upon postsynaptic calcium release

Two molecular mechanisms for synaptic plasticity (researched by the Eric Kandel laboratories) involve the NMDA and AMPA glutamate receptors. Opening of NMDA channels (which relates to the level of cellular depolarization) leads to a rise in post-synaptic Ca2+ concentration and this has been linked to long-term potentiation, LTP (as well as to protein kinase activation); strong depolarization of the post-synaptic cell completely displaces the magnesium ions that block NMDA ion channels and allows calcium ions to enter a cell – probably causing LTP, while weaker depolarization only partially displaces the Mg2+ ions, resulting in less Ca2+ entering the post-synaptic neuron and lower intracellular Ca2+ concentrations (which activate protein phosphatases and induce long-term depression, LTD).

These activated protein kinases serve to phosphorylate post-synaptic excitatory receptors (e.g. AMPA receptors), improving cation conduction, and thereby potentiating the synapse. Also, these signals recruit additional receptors into the post-synaptic membrane, stimulating the production of a modified receptor type, thereby facilitating an influx of calcium. This in turn increases post-synaptic excitation by a given pre-synaptic stimulus. This process can be reversed via the activity of protein phosphatases, which act to dephosphorylate these cation channels


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