Sunday, May 11, 2008

Nervous System Basics IX: CHEMICAL CODING

Angevine's eighth and last organizing principle:

"Chemical Message Coding
The basic function of the nervous system, from which all others derive, is communication, performed (with unsung neuroglial support) by neurons. It depends on special electrical, structural,and chemical properties of these diversified cells with their long processes, on their exploitation and refinement of two basic protoplasmic properties, irritability and conductivity, on their external and internal neuronal morphology featuring multipolar shape and integrative design, almost infinite modes of dendritic and axonal branching, widespread, diversified connections, and specialized organelles, and on their use of chemical substances to encode, deliver and decipher messages of their own and other neurons.

Neural circuits are chemically coded. Neuroanatomy encompasses interneuronal connections and also chemical mediators and transmitters. Neuroactive substances comprise neurotransmitters, neuromodulators, and neurohormones. Their definition in contexts other than site of action, postsynaptic neuronal activity, and corelease of one or more additional neuroactive substances can be misleading. Neurotransmitters are small molecules acting swiftly, locally, and briefly on target cells. Neuromodulators are very small (peptides), regulating but not effecting transmission, and neurohormones are also small, with intrinsic activity mediated by neuronal and other cells, exerting slow, widespread, and enduring influence via the extracellular fluid or bloodstream.

Neurons releasing hormones are quasi-endocrine cells, liberating secretory products from axonal endings into the perivascular space to be conveyed to blood vessels and thence to target organs. The provincial concerns of neurophysiology and endocrinology have fused into neuroendocrinology, as psychoneuroimmunology has united psychobiology, molecular neurobiology, and immunology."

This area of study, neurophysiology, is something I haven't tackled yet to any large extent, still don't know the transmitters from the neurohormones from the chemical neuromodulators, but I'm working on it.

What I like about Angevine's little chemical coding summary is that it is succinct and clear.

Here is more, from Gray's Anatomy:
Neurohormones are included in the range of transmitter activities. They are synthesized in neurones and released into the blood circulation by exocytosis at synaptic terminal-like structures. As with classic endocrine gland hormones, they may act at great distances from their site of secretion. Neurones secrete into the cerebrospinal fluid or local interstitial fluid to affect other cells, either diffusely or at a distance. To encompass this wide range of phenomena the general term neuromediation has been used, and the chemicals involved are called neuromediators".

Some neuromediators do not appear to affect the postsynaptic membrane directly, but they can affect its responses to other neuromediators, either enhancing their activity (increasing the immediate response in size, or causing a prolongation), or perhaps limiting or inhibiting their action. These substances are called neuromodulators. A single synaptic terminal may contain one or more neuromodulators in addition to a neurotransmitter, usually (though not always) in separate vesicles. Neuropeptides are nearly all neuromodulators, at least in some of their actions. They are stored within dense granular synaptic vesicles of various sizes and appearances."

Until recently the molecules known to be involved in chemical synapses were limited to a fairly small group of classic neurotransmitters, e.g. ACh, noradrenaline, adrenaline, dopamine and histamine, all of which had well-defined rapid effects on other neurones, muscle cells or glands. However, many synaptic interactions cannot be explained on the basis of classic neurotransmitters, and it now appears that other substances, particularly some amino acids such as glutamate, glycine, aspartate, GABA and the monoamine, serotonin, also function as transmitters. Substances first identified as hypophyseal hormones or as part of the dispersed neuroendocrine system of the alimentary tract, can be detected widely throughout the CNS and PNS, often associated with functionally integrated systems. Many of these are peptides: more than 50 (together with other candidates), function mainly as neuromodulators and influence the activities of classic transmitters."

More than 50. Looks like I'll be catching up on this for awhile. We must add to this the fact that ATP itself (the molecule which supplies metabolic energy) has been found to be a global (purinergic) neurotransmitter as well. Here is what Gray's Anatomy says about this recent upset to the way the data base on this was once arranged:
"The traditional concept of autonomic neurotransmission is that preganglionic neurones of both sympathetic and parasympathetic systems are cholinergic and that postganglionic parasympathetic neurones are also cholinergic while those of the sympathetic nervous system are noradrenergic. The discovery of neurones which do not use either acetylcholine or noradrenaline (norepinephrine) as their primary transmitter, and the recognition of a multiplicity of substances in autonomic nerves which fulfil the criteria for a neurotransmitter or neuromodulator, have greatly complicated neuropharmacological concepts of the autonomic nervous system. Thus, adenosine 5'-triphosphate (ATP), numerous peptides and nitric oxide have all been implicated in the mechanisms of cell signalling in the autonomic nervous system. The principal cotransmitters in sympathetic nerves are ATP and neuropeptide Y, vasoactive intestinal polypeptide (VIP) in parasympathetic nerves and ATP, VIP and substance P in enteric nerves."

My bold.

Geoffrey Burnstock, who has researched the autonomic nervous system for decades, suspected ATP long ago. Enough other researchers have drawn the same conclusion that it has become accepted, and he wrote a lengthy (140 page) detailed review paper on the history of the discovery. (Physiology and Pathophysiology of Purinergic Neurotransmission 2007).

He's currently (among other things) working on unraveling purinergic mechanosensory transduction and pain with a Swiss company, Roche Bioscience in Palo Alto. Here is an interview with this apparently irrepressible man.


Sam said...

Hello I have been teaching myself about the same things recently!

Here are some interesting references a friend sent me:

Farrant M., Nusser Z. (2005). Variations on an inhibitory theme: Phasic and tonic activation of GABA A receptors Nature Reviews Neuroscience 6, 215-229

Yu A.J., Dayan P. (2005). Uncertainty, neuromodulation, and attention. Neuron 46 (4) 681-692

Dayan P., Huys Q.J.M. (2008). Serotonin, inhibition, and negative mood. PLoS Computational Biology (4) 2

The Farrant & Nusser article is particularly interesting on different types of GABA-mediated inhibition.


dermoneuromodulator "neuroplastician" said...

Thanks for the references Sam.