The brain, neurons and neurotransmission

Basal Thalamus Medulla Cerebellum ganglia oblongata 

Each sensory afferent neuron connects with an interneuron or accessory neuron. These interneurons are located entirely within the CNS, with the majority occurring in the cerebral cortex. They form numerous interconnections and are the means by which all cognitive information, thoughts and feelings, are processed. It should be emphasised that the main role of this processing of information is inhibitory. The sensory receptors provide the CNS with a massive amount of data. The interneurons process and filter this into a limited amount of useful and important informa tion. Conscious information processing forms just one part of this activity. A great deal of brain activity is concerned with routine processes, which continue without conscious awareness. 

At the end of this processing sequence, some of the interneurons connect with motor efferent neurons. These motor efferents leave the CNS and stimulate the peripheral effectors. Most of the effectors are muscles of various types smooth, 

Sensory afferent neuron Synapse Synapse Motor efferent neuron 

O Sensory receptor Cell body (perikaryon or soma) Synaptic bouton/button 

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Table 33.3 Thiamine diphosphate deficits reduce acetyl-CoA levels in sub-cellular compartments of the brain neurons, suppressing their viability and cholinergic neurotransmission. Data from Bielarczyk et al. (2005), Bizon-Zygmanska et al. (2011) and Jankowska-Kulawy et al. (2010) expressed as means SEM in pmol/mg protein ( = 5-20 experiments). Italics refer to fractions of acetyl-CoA and acetylcholine provided through the ATP itrate lyase pathway (see Figure 33.1). Bold numbers refer to nonviable cell fractions assayed by trypan blue exclusion assay and expressed as a percentage of the whole cell population.

An increased focus on those processes that regulate neurotransmission and ceUular functions both of neurons and of the other half of the brain, the ghal ceU family, is expected. 

Typically, neurotoxic effects of drugs on monoamine neurons have been assessed from reductions in brain levels of monoamines and their metabolites, decreases in the maximal activity of synthetic enzymes activity, and decreases in the active uptake carrier. In the present study, the traditional markers described above have been used, including the measurement of the content of monoamines and their metabolites in brain at several different timepoints following drug administration. Since reports in the literature have documented that MDMA and MDA can inhibit the activity of tryptophan hydroxylase (TPH), the rate-limiting enzyme in serotonin synthesis (Stone et al. 1986 Stone et al. 1987). it is unclear whether MDMA-induced reductions in the content of serotonin and its metabolite 5-hydroxyin-doleacetic acid (5-HlAA) may be due to suppressed neurotransmission in otherwise structurally intact serotonin neurons or may represent the eonsequenee of the destruction of serotonin neurons and terminals. 

The triptans are considered specific therapies in that they target the pathophysiology underlying migraine.33 They abort headache through beneficial effects on neuronal imbalances.11 Triptans inhibit neurotransmission in the trigeminal complex and activate serotonin lb/Id pathways that modulate nociception in the brain stem. They also decrease the release of vasoactive peptides leading to vascular reactivity and pain.34 Triptans are a welcome addition to the therapeutic armamentarium in that they are available in intranasal, subcutaneous, and oral... 

The AMPA receptors mediate the majority of fast excitatory neurotransmission in the mammalian brain. The rapid kinetics and the low Ca permeability make these receptors ideal for fast neurotransmission without sufficient changes in the intracellular calcium concentration to activate Ca2+-dependent processes. The NMDA receptors are co-localized with the AMPA receptors on many synapses, but the slow kinetics of the NMDA receptor minimize the receptor activation after a single presynaptic glutamate release where the neuron quickly repolarizes, resulting in Mg2+ block... 

Ammonia has deleterious effects on brain function by direct and indirect mechanisms. Concentrations of ammonia in the 1-2 mmol/1 range, equivalent to those reported in the brain in liver failure, impair postsynaptic inhibition in cerebral cortex and brainstem by a direct effect on Cl extrusion from the postsynaptic neuron. Millimolar concentrations of ammonia also inhibit excitatory neurotransmission. Synaptic transmission from Schaffer collaterals to CA1 hippocampal neurons is reversibly depressed by 1 mmol/1 ammonia, and the firing of CA1 neurons by iontophoretic application of glutamate is inhibited by 2 mmol/1 ammonia [10],... 

Over 100 years ago, a debate was raging between the two most famous neuroscientists in the world concerning the nature of the nervous system. Golgi believed that all neurons were connected in a nerve net or syncytium whereas Ramon y Cajal believed that neurons were separated from each other by tiny spaces called synapses. Cajal proved to be correct, and it was later learned that neurons communicate across the synapse by releasing chemical substances known as neurotransmitters or by releasing electrical charges. Because chemical neurotransmission is much more common than electrical transmission, especially in the brain, and it is chemical neurotransmission that is modulated by psychiatric medicines, our discussion will focus on the chemotransmitter process. In simplest terms, the process of chemical neurotransmission occurs in three steps neurotransmitter production, neurotransmitter release, and neurotransmitter action on specific receptors. 

This book adds to numerous preceding texts on consciousness the relatively new concept that particular neurotransmitters may be central to the process. As outlined in the Preface, communication between neurons is essential for consciousness and such communication, on the timescale applicable to conscious perception, is principally mediated by chemical neurotransmission. As Susan Greenfield (2000) points out in The Private Life of the Brain , acetylcholine may enable a whole population of cells to become more important than individual units, a kind of neuroscientific Marxism If the concept of transmitter NCC is incorporated into future discussions of the neurobiology of consciousness, or adds a further dimension to the neuropharmacology of disorders of the brain which affect conscious awareness, this book will have more than served its purpose. 

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