Consciousness neurotransmitters

PERRY, Elaine, Heather ASHTON and Allan YOUNG (eds.) Neurochemistry of Consciousness. Neurotransmitters in mind. 2001. 

Neurochemistry of Consciousness Neurotransmitters in mind Edited by Elaine Perry, Heather Ashton and Allan Young... 

How the different neurotransmitters may be involved in the initiation and maintenance of some brain disorders, such as Parkinson s disease, epilepsy, schizophrenia, depression, anxiety and dementia, as well as in the sensation of pain, is then evaluated and an attempt made to see how the drugs which are used in these conditions produce their effect by modifying appropriate neurotransmitter function (section C). The final section (D) deals with how neurotransmitters are involved in sleep and consciousness and in the social problems of drug use and abuse. 

The concept of chemical neurotransmission originated in the 1920s with the classic experiments of Otto Loewi (which were themselves inspired by a dream), who demonstrated that by transferring the ventricular fluid of a stimulated frog heart onto an unstimulated frog heart he could reproduce the effects of a (parasympathetic) nerve stimulus on the unstimulated heart (Loewi Navratil, 1926). Subsequently, it was found that acetylcholine was the neurotransmitter released from these parasympathetic nerve fibers. As well as playing a critical role in synaptic transmission in the autonomic nervous system and at vertebrate neuromuscular junctions (Dale, 1935), acetylcholine plays a central role in the control of wakefulness and REM sleep. Some have even gone as far as to call acetylcholine a neurotransmitter correlate of consciousness (Perry et al., 1999). 

Perry, E., Walker, M., Grace, J. 8r Perry, R. (1999). Acetylcholine in mind a neurotransmitter correlate of consciousness Trends Neurosci. 22, 273-80. 

The symptoms of HE are thought to result from an accumulation of gut-derived nitrogenous substances in the systemic circulation as a consequence of shunting through portosystemic collaterals bypassing the liver. These substances then enter the CNS and result in alterations of neurotransmitters that affect consciousness and behavior. 

Figure 9.30 Flow diagram of the energy chain from food to essential processes in human life. The ATP utilised by the NayK ATPase maintains the ion distribution in nerves that is essential for electrical activity and, in addition, maintains neurotransmitter synthesis, both of which provide communication in the brain and hence consciousness, learning and behaviour (Chapter 14). ATP utilisation by myosin ATPase is essential for movement and physical activity. ATP utilisation by the flagellum of sperm is essential for reproduction and ATP utilisation for synthesis of macromolecules is essential for growth.

With TMS, a brief but powerful electric current is passed through a small coil held against the scalp of a conscious patient. This generates a powerful local magnetic field which passes unimpeded through the skull and induces a weaker, less focused electric current within the brain. Due to the non-invasive nature of this method, the important physiological effects of TMS are likely to be a consequence of the density of the electric current and the electric field which is induced in the cortex. It is believed that the induced electrical fields cause neuronal depolarization which changes the neurotransmitter release mechanisms. 

The S-enantiomer of citalopram (escitalopram) is over 100 times more potent in inhibiting the reuptake of 5-HT into brain slices than the R-form and is devoid of any activity at the neurotransmitter of other receptor types (racemic citalopram has an affinity for histamine receptors and causes sedation). In in vivo studies, escitalopram is more potent than the R-form or the racemate in releasing 5-HT in the cortex of conscious rats it has been... 

The alterations in neurotransmitter activity which trigger or accompany the onset of natural sleep and distinguish slow wave or non-REM from REM sleep, provide one of the most compelling arguments in favour of chemical neurotransmission being specifically involved in mechanisms of conscious awareness. For an extensive review on neurochemistry and sleep, see Gottes-man (1999). 

Consistent with alterations in neurotransmission associated with sleep onset, SWS and REM sleep (Chapters 6-8), drugs affecting neurotransmitter function have specific effects on the sleep-wake cycle. Thus reduced levels of conscious-... 

The state of conscious awareness, with orientation of self in time and space, depends on hnely tuned and accurately co-ordinated activity in multiple neuronal networks in the brain (Park Young, 1994). Such activity involves parallel processing in many cortical and subcortical pathways including arousal and memory systems (Chapters 3 and 4) and systems involved in mood (Chapters 5 and 18) and utilises an orchestra of many neurotransmitters. The whole ensemble appears to be synchronised by high frequency (40+ Hz) oscillatory electrical activity which binds the component parts together (Llinas et ah, 1998 Tallon-Baudry Bertrand, 1999). 

Some of the many factors that can cause delirium are shown in Figure 1. Some authors (Flacker Lipsitz, 2000) have concluded that there is probably no hnal common pathway to delirium, suggesting instead that delirium is the hnal common symptom that can result from aberrations in numerous different transmitter pathways and pathological processes. Since normal brain function, and especially consciousness, depends on accurate communication between a very large number of neurotransmitter systems, the latter conclusion seems more rational. To search for a hnal common pathway may be to oversimplify... 

Hallucinations can be caused by any of the drugs that induce delirium, described above. Drug-induced hallucinations can also occur in the presence of a clear consciousness and can be caused by a large number and wide variety of drugs (Table 2). To some extent the hallucinations are characteristic of the inducing drug (Table 3) and may reflect perturbations of particular neurotransmitters or brain areas. Only a sample of drug-induced hallucinations are described here. 

In DLB, fluctuations in both the level of consciousness and in the content of consciousness (hallucinations and delusions) develop. These alterations, together with much of the ensuing cognitive impairment, fluctuate to such an extent that patients can transiently return to being symptom-free in the course of the disease. This temporal pattern implicates functional as opposed to structural neuropathological abnormalities in symptom aetiology. Several neurotransmitter correlates have been identified in autopsy tissue from retrospectively, and more recently, prospectively assessed patients. 

The neurochemistry of schizophrenia has been considered in a variety of ways by numerous investigators and most have, as here, focussed on the role of abnormalities and/or dysfunction of brain neurotransmitter systems in the disease. Implicit in a book on the neurochemistry of consciousness is the assumption that this chapter will address the neurochemical basis of the disturbance (s) of consciousness that occurs in schizophrenia. Consciousness in its particular and generally-understood meaning is not obviously distorted in schizophrenia, although schizophrenic patients clearly have a different, or abnormal experience of the external world—their conscious awareness is disturbed. 

This chapter is concerned with the neurochemical basis of developmental disability which is considered here in two forms the globally delayed or halted development seen in mental retardation, and the more circumscribed pattern of disordered development of autism. A range of deficits of important key aspects of consciousness are apparent in both conditions. Of particular relevance to consciousness are the cognitive and behavioural impairments in attention, concentration, memory, information processing and social behaviour which are commonly present. Consideration of aberrant neurotransmitter activities in these developmental deficits may provide insights into the role of neurotransmitters in consciousness. 

This diversity of mental retardation, in both cause and phenotype, carries important implications for consideration of the biochemistry of consciousness. On the one hand, because this is an investigation of multiple causalities—including, for example, inborn errors of metabolism, each of which has its own unique biochemical profile (Cook Leventhal, 1996), it may not prove possible to identify specific neurotransmitter abnormalities which are common to mental retardation as such. On the other hand common themes concerning key neurotransmitters may be identified from studies of mental retardation. Altered neurotransmitter functioning associated with the severity of mental retardation is open to different interpretations, either reflecting fundamentally impaired development of cerebral structure or a more general impairment of central transmitter activity and functioning. 

If there is an association between the extent or severity of abnormal neurotransmitter functioning and the global measure of severity of autism, the direction and mechanism of causality may still be unclear (as has been discussed in mental retardation). However, neurotransmitter correlates of specific aspects of autism, such as social isolation or obsessional behaviour, are likely to be more revealing and of greater relevance to the study of consciousness. 

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. 

Consciousness. 2. Neurotransmitters. 3. Neurochemistry. 4. Neurobehavioral disorders. 1. Perry E.K. (Elaine K.) 11. Ashton, Heather. 111. Young, Allan, 1983- IV. Series. 

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