Showing papers in "Progress in Brain Research in 1986"
TL;DR: The functional and the morphological properties of the spinal visceral afferent neurons, supplying the abdominal and pelvic organs, are discussed, including special emphasis has been placed on the visceral nociception and pain.
Abstract: Publisher Summary This chapter discusses the functional and the morphological properties of the spinal visceral afferent neurons, supplying the abdominal and pelvic organs. These neurons are involved in the regulation of the visceral functions, in sensations and in various spinal and supraspinal reflexes. Special emphasis has been placed on the visceral nociception and pain. The spatial resolution of the sensations that can be elicited from the viscera is relatively vague and can be fully explained, by the segmental width of the afferent inflow from each viscus. Most spinal visceral afferent units have various common functional properties: they are silent or display a low rate of ongoing activity; their axons are unmyelinated or thinly myelinated (conduction velocity below 2 m/second and mostly below 20 m/second, respectively); their receptive fields consist of from 1-9 mechanosensitive sites located in the mesenteries on the serosal surface or on the walls of the organs; local pressure in their receptive fields elicits slowly adapting responses; they respond to distensions and contractions of the viscera and to stretching of their mechanosensitive endings; they respond to various chemical stimuli applied in their receptive fields.
374 citations
TL;DR: This chapter proposes a reevaluation of terminology and notation to encompass the realization that every neuron has multiple chemical messengers and that each neuron may transmit multiple messages.
Abstract: Publisher Summary This chapter describes earlier observations that lead to the view that there is a precise multiple neurochemical coding of the subpopulations of enteric neurons, which form the intricate neuronal circuits that control intestinal functions. In the mammalian enteric nervous system, there are as many neurons as in the spinal cord, and there are numerous different enteric neurons characterized by the substances they contain, their shapes, and their projections. Most gastrointestinal functions—that is, motility with its vast repertoire of behavior, blood flow, and secretion and absorption of water and electrolytes—are known to be controlled or influenced by autonomic nerves. The discovery of coexistence of chemical messengers in neurons prompted the systematic immunohistochemical investigation of the patterns of coexistence of messengers in enteric neurons. The chapter discusses the methods for the simultaneous localization of two antigens and the problems encountered and demonstrates some of the applications of studies of coexistence of multiple messengers. This principle of organization of the enteric nervous system provides an extremely valuable framework in working out its circuitry and assists in identifying the possible roles of the multiple chemical messengers in individual neurons. The chapter proposes a reevaluation of terminology and notation to encompass the realization that every neuron has multiple chemical messengers and that each neuron may transmit multiple messages.
286 citations
TL;DR: By using the blood-perfused cat or pig spleen as an experimental model, it has been demonstrated by earlier studies that nerve stimulation causes a co-release of NA and NPY-LI, suggesting a chemical heterogeneity and a morphological basis for a functional differentiation of the sympathetic nerves.
Abstract: Publisher Summary This chapter focuses on some recent advances in studies on the co-existence of peptides with acetylcholine (Ach) and noradrenaline (NA) in certain autonomic nerves, as well as on the occurrence of multiple peptides in sensory nerves Noradrenaline has for long been known to be the primary transmitter of peripheral sympathetic neurons with minor exceptions—for example, the sympathetic innervation of sweat glands, which is cholinergic Immunohistochemical evidence has suggested that a member of the pancreatic polypeptide family—avian pancreatic polypeptide (APP)—has a widespread neuronal localization in mammals Only a proportion of sympathetic NA nerves seems to contain the NPY-like peptide and these neurons innervate target organs such as blood vessels, the muscle of the heart, spleen, and vas deferens Other populations of sympathetic neurons projecting to, for instance, exocrine elements in certain salivary glands or brown fat cells do not contain NPY, suggesting a chemical heterogeneity and a morphological basis for a functional differentiation of the sympathetic nerves Sympathetic nerve stimulation is accompanied not only by release of NA but also of NPY-LI Thus, by using the blood-perfused cat or pig spleen as an experimental model, it has been demonstrated by earlier studies that nerve stimulation causes a co-release of NA and NPY-LI Intermittent stimulation with bursts of impulses at a high frequency enhances selectively the release of NPY-LI compared to NA
268 citations
TL;DR: This chapter outlines current views about the organization of neural circuitry underlying the integration of stress responses, with special emphasis on the hypothalamic regulation of adrenocorticotropic hormone (ACTH) release from the anterior pituitary.
Abstract: Publisher Summary This chapter outlines current views about the organization of neural circuitry underlying the integration of stress responses, with special emphasis on the hypothalamic regulation of adrenocorticotropic hormone (ACTH) release from the anterior pituitary. The adrenal gland plays a major role in such responses. The release of glucocorticoid hormones from the adrenal cortex is influenced by ACTH, while the release of catecholamines from the adrenal medulla is mediated primarily by the sympathetic nervous system. The most influential unifying hypothesis in this field was advanced by Hans Selye, who proposed that most stressors induce two classes of response. One, which is called the “stress response,” is common to all stressors and involves the release of ACTH and adrenal catecholamines, which may have different time courses and lead to different functional consequences. The other consists of responses that are appropriate for individual stressors. The brain is involved in processing all the classes of stimuli that can be regarded as stressors and is responsible for coordinating the groups of appropriate autonomic, endocrine, and behavioral responses. Recent anatomical and physiological evidence is beginning to clarify the organization of specific neural circuits mediating adrenal steroid and catecholamine release during the stress response, as well as the other endocrine, autonomic, and behavioral responses specific to hypovolemia. The paraventricular nucleus of the hypothalamus (PVH) in this circuitry regulates ACTH release from the anterior pituitary; it also plays an important role in the secretion of vasopressin from the posterior pituitary, and modulates baroreceptor reflexes.
228 citations
TL;DR: The progress which has been made toward integrating the immunocytochemical data with the emerging picture of the spinal circuitry derived from anatomical and electrophysiological work are also discussed.
Abstract: Publisher Summary This chapter discusses the wealth of immunocytochemical data about the neurochemicals (the classical neurotransmitters and the neuropeptides) that are found in the mammalian spinal cord. The chapter focuses on those regions of the spinal cord that are likely to be concerned with somatosensation rather than movement or autonomic function. Relay nuclei in the central nervous system characteristically include three major functional components: the terminals of primary afferent neurons that relay signals from distant sites; intrinsic neurons, which include output neurons that transmit signals to distant sites, and local circuit neurons that modify sensory transmission in a restricted region; and the axon terminals of extrinsic neurons arising from distant sites. The spinal dorsal horn is no exception to this common organization. The progress which has been made toward integrating the immunocytochemical data with the emerging picture of the spinal circuitry derived from anatomical and electrophysiological work are also discussed.
212 citations
TL;DR: Results demonstrating that neurons often contain more than one chemical compound demonstrate that multiple messengers may provide the means for increasing the capacity for information transfer in the nervous system.
Abstract: Publisher Summary This chapter discusses results demonstrating that neurons often contain more than one chemical compound. The different types of coexistence situations are described, including (1) a classical transmitter and one or more peptides, (2) more than one classical transmitter, and (3) a classical transmitter, a peptide, and adenosine triphosphate (ATP). The functional significance of these histochemical findings is at present difficult to evaluate, but in studies on the peripheral nervous system evidence has been obtained that classical transmitter and peptide are coreleased and interact in a cooperative way on effector cells. In addition to enhancement, there is evidence that other types of interactions may occur—for example, the peptide may inhibit the release of the classical transmitter. Also in the central nervous system (CNS), indirect evidence is present for similar mechanisms—that is, to strengthen transmission at synaptic (or non-synaptic) sites and for the peptide inhibition of release of a classical transmitter. Multiple messengers may provide the means for increasing the capacity for information transfer in the nervous system.
212 citations
TL;DR: The histological studies discussed in the chapter have provided evidence that the NTS, and its immediate vicinity, is the sole site of termination in the medulla of the afferents contained in the IXth and Xth cranial nerves and their various peripheral branches.
Abstract: Publisher Summary This chapter discusses the current literature relating to the afferent innervation of the NTS from cardiopulmonary receptors and the arterial baroreceptors and chemoreceptors The processing of these inputs has been described in this chapter and the influence of the descending inputs from the diencephalon on these mechanisms has also been described While these afferent inputs exert powerful reflex influences and modify the state of arousal, their role in conscious perception and in the control of visceral sensation remains to be documented The histological studies discussed in the chapter have provided evidence that the NTS, and its immediate vicinity, is the sole site of termination in the medulla of the afferents contained in the IXth and Xth cranial nerves and their various peripheral branches Traditional neurophysiological recording studies have lent support to this contention, although these failed to reveal the specific patterns of projection of the individual classes of afferent contained within these nerves
190 citations
TL;DR: This chapter considers a particular type of cell that discharges in relation to the initiation of saccades made to remembered targets in the basal ganglia of the substantia nigra.
Abstract: Publisher Summary The impetus for the study of the basal ganglia in relation to vision and eye movements comes from what one know about the connection of this structure to the superior colliculus (SC), a structure recognized as a critical station for the initiation of saccadic eye movements. One output pathway of the basal ganglia, the pars reticulata of the substantia nigra (SNr), projects to the intermediate layers of the SC. These cells in the intermediate layers discharge before saccadic eye movements when those eye movements are directed to one region of the visual field, the movement field of the cells. Stimulation of these intermediate layer cells leads to the initiation of saccadic eye movements to the area of movement field of the adjacent cells. Finally, cells in the intermediate layers of the SC have direct projections to the brainstem areas (mesencephalic reticular formation, MRF; paramedian pontine reticular formation, PPRF) where pre-oculomotor neurons are located. The SNr projection to the SC represents one of the most prominent inputs to the intermediate layers of the SC. This chapter is intended to summarize those aspects of the experiments that are related to the initiation of saccadic eye movements. After describing the general characteristics of cells in the SNr, the chapter considers a particular type of cell that discharges in relation to the initiation of saccades made to remembered targets.
136 citations
TL;DR: The bistable properties of motoneurones allow them to act as very simple integrators, like flipflops, which are set at one of two levels by short excitatory or inhibitory inputs, however, when the whole mot oneuronal pool is considered, many different levels can be maintained by recruitment of new units.
Abstract: Publisher Summary Brief sensory inputs to intact conscious subjects commonly trigger complex long-lasting motor responses, in which higher cerebral mechanisms, or even voluntary action, may be integrative parts. However, long-lasting motor discharge following brief afferent stimulation is also observed in reduced preparations, such as decerebrate or spinal animals. Reverberating activity in closed neuronal loops has been postulated to be an important integral mechanism underlying various phenomena, ranging from temporal integration in the vestibulo-ocular reflex to maintenance of “initial” memory. Such far-reaching notions stand in sharp contrast to the virtual absence of experimental evidence for sustained reverberating activity in well-defined neuronal circuits. Present quantitative knowledge of the sensory input and efferent output in the vestibulo-ocular reflex has prompted several investigators to postulate a neuronal integrator in the intervening CNS. There have been several attempts to model this neuronal integrator. The assumption common for all these models is a network of neurones with positive feedback loops. The bistable properties of motoneurones allow them to act as very simple integrators, like flipflops, which are set at one of two levels by short excitatory or inhibitory inputs. However, when the whole motoneuronal pool is considered, many different levels can be maintained by recruitment of new units.
136 citations
TL;DR: This chapter discusses the neuroanatomical experiments that examine the segmental distribution and the central projections of the afferent neurons innervating the urogenital system, large intestine, heart, and upper abdominal organs and the identity of the peptide neurotransmitters in visceral afferent pathways.
Abstract: Publisher Summary This chapter discusses the neuroanatomical experiments that examine the segmental distribution and the central projections of the afferent neurons innervating the urogenital system, large intestine, heart, and upper abdominal organs and the identity of the peptide neurotransmitters in visceral afferent pathways. Recently, developed neuroanatomical tracing methods have yielded important advances in the knowledge of the organization of visceral afferent pathways at various levels of the spinal cord. Horseradish peroxidase tracing experiments have shown that afferent projections from a number of visceral organs exhibit a similar pattern of termination in the spinal cord, and that this pattern is markedly different from that of the somatic afferent neurons that innervate the skin. In addition, neurochemical studies, in which the axonal tracing techniques were combined with immunocytochemistry, revealed that a large percentage of the visceral afferent neurons exhibit neuropeptide immunoreactivity. These findings raised the possibility that neuropeptides may be important transmitters or neuromodulators in the visceral afferent systems.
131 citations
TL;DR: The thoracic and abdominal distribution of the vagi that are available for a number of species are described and the question of whether they are vagal remains, as the vagal and the splanchnic nerves often share the same terminal course.
Abstract: Publisher Summary This chapter describes the thoracic and abdominal distribution of the vagi that are available for a number of species. Several points arise from the observations of the gross anatomy of the vagus. First, apart from the stomach and liver, the remaining abdominal viscera (e.g., pancreas) do not receive macroscopically identifiable discrete branches. This means that their afferent innervation can only be studied, by either using tracer techniques or recording afferent activity at a distant site, where the vagus is “contaminated,” by afferents from the other organs. Even in areas of the gut (e.g., small intestine), where discrete nerve bundles can be identified and activity recorded relatively easily, the question of whether they are vagal remains, as the vagal and the splanchnic nerves often share the same terminal course.
TL;DR: All the available experimental evidence supports the main postulates of the “convergence-projection” theory of referred visceral pain, which indicates that “true” visceral pain is not due to the activation of specific visceral sensory channels, but, more likely, is the consequence of the spread of the visceral lesion to the regions innervated by somatic nerves, whose stimulation leads to restricted and well-localized experiences of the deep pain.
Abstract: Publisher Summary This chapter discusses the lower thoracic spinal cord that receives the bulk of the visceral sensory input, mediated by the sympathetic splanchnic nerves These afferent fibres transmit nociceptive signals, from many abdominal viscera, to the spinal cord, where the visceral and somatic sensory information are jointly processed All the available experimental evidence supports the main postulates of the “convergence-projection” theory of referred visceral pain In spite of extensive electrophysiological investigations of the thoracic spinal cord, no pathway has been found, carrying, exclusively, the visceral sensory information This indicates that “true” visceral pain is not due to the activation of specific visceral sensory channels, but, more likely, is the consequence of the spread of the visceral lesion to the regions innervated by somatic nerves, whose stimulation leads to restricted and well-localized experiences of the deep pain Therefore, excitation of the visceral sensory receptors always evokes sensory experiences that are ill-localized, poorly discriminated, and referred to as somatic structures
TL;DR: This chapter summarizes the current knowledge about the circadian system and its organization and provides an overview of chronobiological studies in which age or dementia has been treated as independent variable and indicates possible fruitful future directions of the research related to aging and circadian rhythms.
Abstract: Publisher Summary This chapter summarizes the current knowledge about the circadian system and its organization and provides an overview of chronobiological studies in which age or dementia has been treated as independent variable. It also discusses the relevance of considering circadian variations in gerontology and indicates possible fruitful future directions of the research related to aging and circadian rhythms. Circadian rhythms—that is, rhythmic changes with a periodicity of approximately 24 hours—can be observed in organisms ranging from protozoans to humans. Organization in the dimension time is a pervasive characteristic of living systems. The circadian timekeeping system appears to be changed during aging in both animals and humans. Because of the growing interest in gerontology, the number of functional systems for which age-related changes are described is continuously increasing. In contrast to some other systems sensitive to the effects of aging, the circadian timekeeping system is directly implicated in the organization of various important physiological functions. The reduction in suprachiasmatic nuclei (SCN) cell number found in old age and even stronger in Alzheimer's disease represents a possible morphological correlate of circadian rhythm alterations in old age.
TL;DR: This chapter describes the alterations in dendritic extent as potential compensatory responses to age-related neuronal loss in selected brain regions and discusses the apparent breakdown of this compensatory response in Alzheimer's disease and in extreme old age in some brain regions.
Abstract: Publisher Summary This chapter describes the alterations in dendritic extent as potential compensatory responses to age-related neuronal loss in selected brain regions and discusses the apparent breakdown of this compensatory response in Alzheimer's disease and in extreme old age in some brain regions. In considering alterations in dendritic extent as compensatory changes, changes taking place in the surrounding microenvironment of the dendritic trees being considered are also examined in the chapter. Scientists developed a model of two interacting classes of influences on dendritic extent in the aging brain. The loss of neighboring neurons is a proliferative influence in normal aging, at least up to some limit, which seems to be exceeded in very old age in some brain regions. This proliferative influence seems to be deficient in Alzheimer's disease. Partial denervation is a regressive influence in the aged brain, just as it is during earlier periods in the developmental continuum. There are brain regions in which both of these influences are operating. It is suggested that when both influences are operating on the same cell in the normally aging brain, the final effect on the dendritic tree will be a reflection of the net sum of these two influences. The rat cerebellar Purkinje cells represent one example in which there is both neighbor neuron death and an apparent loss of parallel fiber input.
TL;DR: This chapter provides an overview of the status of this organelle in relation to the aging process with the realization that mature lipofuscin is formed by a dynamic process during which morphology and chemical composition of the organelle undergo progressive modifications.
Abstract: Publisher Summary Most of the cell types in the bodies of multicellular organisms exhibit an age-associated increase in the content of a specific organelle, which has been given a variety of different names, including, age pigment, chromolipid, lipopigment, and lipofuscin. The accretion of lipofuscin is the only consistent age-related morphological alteration detected so far. This chapter provides an overview of the status of this organelle in relation to the aging process. The key to the understanding of the nature and potential significance of lipofuscin is the realization that mature lipofuscin is formed by a dynamic process during which morphology and chemical composition of the organelle undergo progressive modifications. In addition, the composition of lipofuscin may vary in different cell types and under different dietary and physiological conditions. The structure and composition of lipofuscin is best understood in context of the processes involved in the formation of lipofuscin. The most widely accepted view, based on electron microscopic, cytochemical, and biochemical studies, is that the initial step in the formation of lipofuscin is the autophagocytosis of cytoplasmic components.
TL;DR: Evidence that the durability of synaptic plasticity is regulated by protein kinase C and its substrates is provided and evidence that implicates protein Kinase C as participating in the regulation of several different cellular processes is reviewed.
Abstract: Publisher Summary This chapter describes the role of protein kinase C in the expression of synaptic plasticity. One theme to emerge from the studies presented in the chapter is that protein kinase C specifically regulates the durability or persistence of the enhanced synaptic response, possibly by preventing the decay of the response. It does not appear to play a role in the response initiation stages. Another theme is that protein kinase C, as a multifunctional enzyme, may be capable of organizing the major cellular events underlying the persistence of synaptic plasticity by regulating the phosphorylation state of different substrate proteins. The chapter provides evidence that the durability of synaptic plasticity is regulated by protein kinase C and its substrates and reviews evidence that implicates protein kinase C as participating in the regulation of several different cellular processes. Data from acutely anesthetized and chronic preparations indicated that alterations in protein F1 phosphorylation is not an immediate response to high-frequency stimulation, but have a relatively slow onset and persisted for several days. Moreover, these effects are selective for protein F1.
TL;DR: Cells from the principal and minor placodes, local thickenings of the general head and trunk ectoderm of the embryo, provide a variety of neuroectodermal contributions to both the nervous system and the DNES, providing the basis for the establishment of a diffuse neuroendocrine system (DNES).
Abstract: Publisher Summary The co-existence of neuronal messengers of the two classes—amine and peptide—in endocrine cells widely distributed throughout the body was laid down as the cornerstone of the original amine precursor uptake and decarboxylation (APUD) concept. The APUD cells constitute a diffusely distributed collection of neuroendocrine cells that may fairly be described as a system. The manifestly neuronal properties of the cells signify only neuroendocrine function and not a neuroectodermal origin. These premises provide the basis for the establishment of a diffuse neuroendocrine system (DNES). Cells from the principal and minor placodes, local thickenings of the general head and trunk ectoderm of the embryo, provide a variety of neuroectodermal contributions to both the nervous system and the DNES. Cells from the rhombencephalic neural crest make a similar double contribution. Most of the neurons in the cranial sensory ganglia are derived from the neural crest but the trigeminal has neurons of mixed placodal and crest origin. In the trunk ganglia, on the contrary, all the neurons are placodal and the crest contributes only the glial satellite cells.
TL;DR: A closer understanding of the mechanisms underlying the matching of certain temporal demands for perception and motor control is an intriguing problem for future research.
Abstract: Publisher Summary The time control of self-initiated voluntary limb movements is more difficult to assess than that in the oculomotor system, where saccadic and pursuit eye movements are regarded as the products of two independent control systems. The different velocities of the two types of eye movement depend on vestibular and visual inputs as well as on movement amplitude. In contrast to these different types of eye movements, velocity control in the skeletal motor system is continuous, such that limb muscles can produce movements resembling the pursuit or saccadic type of eye movements. In spite of this continuum of possible performances, it is a widely held view that in the skeletal motor system ballistic and ramp movements represents different categories. A difficulty in a comparative analysis of time control in the two systems lies in their different accessibility to examination. Eye movements can be examined in response to visual and vestibular inputs and described in terms of input-output relationships. In reflex studies, this is also possible for limb movements. However, the wide range of input variables and of possible performances of limb movements makes it difficult to explore the control strategies relevant for their performance. A closer understanding of the mechanisms underlying the matching of certain temporal demands for perception and motor control is an intriguing problem for future research.
TL;DR: The conceptual foundations of a theory-based approach to the use of event-related brain potential (ERPs) are introduced, in contrast to a nosological approach, which has been of great benefit in developing a diagnostic measure for multiple sclerosis based on the latency of brain responses elicited by moving checkerboards.
Abstract: Publisher Summary This chapter introduces the conceptual foundations of a theory-based approach to the use of event-related brain potential (ERPs), in contrast to a nosological approach. The chapter provides description of a series of the studies of P300 in aged subjects conducted in laboratory that serves to illustrate an approach to the use of ERPs in cognitive psychophysiology. The degree to which the increase in P300 latency is indeed a specific indicator of senile dementia has proven somewhat controversial. Increases in P300 latency do tend to occur in association with other pathologies. The starting point for a nosological study is the availability of groups of clinically diagnosed patients, as well as an adequate control group of non-patients. The strategy is empirical. Given that the studied groups are known to be proper representatives of the diagnostic classes of interest, then any measure that discriminates among the groups is potentially useful. This approach has, for example, been of great benefit in developing a diagnostic measure for multiple sclerosis based on the latency of brain responses elicited by moving checkerboards. However, the success of the nosological approach is contingent on the specificity of the deficit and the certainty with which patients can be diagnosed clinically.
TL;DR: This chapter discusses the present knowledge of the organization and chemistry of peptidergic visceral afferents, with particular reference to the innervations of the gastrointestinal tract and to the distribution of the peripheral terminals.
Abstract: Publisher Summary The chapter discusses the present knowledge of the organization and chemistry of peptidergic visceral afferents, with particular reference to the innervations of the gastrointestinal tract and to the distribution of the peripheral terminals. Although it may be possible to identify afferents on the basis of other neurochemical properties, e.g., fluorideresistant acid phosphatase histochemistry, serotonin uptake, tyrosine hydroxylase activity, and adenosine deaminase, the physiology of these sub-types of the afferent neurones is less clear than that of the peptidergic afferents. The idea that biologically active peptides might be localized in afferent fibres can be traced to the identification, by bioassay of the substance P in the dorsal root and the vagal nerve extracts. Much of the recent progress depends on the use of radioimmunoassay and immunohistochemistry. However, these experimental approaches are not sufficient for the unequivocal identification of a particular peptide.
TL;DR: This chapter focuses on the evidence for adenosine triphosphate (ATP) as a cotransmitter in adrenergic and cholinergic neurons, and how they help each other terminate neurotransmission by acting on prejunctional receptors to inhibit the release of transmitter.
Abstract: Publisher Summary This chapter focuses on the evidence for adenosine triphosphate (ATP) as a cotransmitter in adrenergic and cholinergic neurons. Several studies in the past have indicated that on using tritium-labelled adenosine and noradrenaline (NA), ATP is released together with NA from sympathetic nerves supplying the rabbit aorta and portal vein. The coexistence of NA and ATP has also been demonstrated in rabbit ear artery, dog basilar artery, and rabbit pulmonary artery. ATP, as well as NA, release from guinea-pig portal vein has been shown to be abolished following sympathectomy. It has also been indicated that ATP is released as a cotransmitter with NA from sympathetic nerves supplying the vas deferens, taenia coli, nictitating membrane, a number of blood vessels, and frog heart. The proportion of ATP to NA varies considerably in sympathetic nerves supplying different organs and in different species, and it is also likely that various peptides coexist with ATP and NA in different sympathetic nerves, particularly neuropeptide Y, but also somatostatin, enkephalin, vasoactive intestinal polypeptide, and vasopressin-like peptide. The cotransmission of ATP and NA involves different postjunctional mechanisms: ATP produces contractions via an electromechanical coupling mechanism involving voltage-dependent Ca 2+ channels, while NA produces contractions via a spike-independent mechanism, involving receptor-operated Ca 2+ channels. ATP and NA act synergistically to potentiate each other's actions, and they help each other terminate neurotransmission by acting on prejunctional receptors to inhibit the release of transmitter.
TL;DR: This chapter describes a more logical rationale to classify models into types and to give a few examples of each type.
Abstract: Publisher Summary This chapter discusses the animal models in psychiatric research. The chapter describes a more logical rationale to classify models into types and to give a few examples of each type. The animal models in psychiatric research can be conveniently classified into four types, based on the principles of (1) pharmacological isomorphism, (2) symptom similarity, (3) gene transfer, and (4) cross-species psychological processes. Isomorphism models are useful for elucidating mechanisms of drug action, but are not able to step outside the existing class of therapeutic agents. Symptom similarity models escape this circularity, but suffer from an inherent arbitrariness, because of the multiplicity of behaviors that are disturbed in the major psychoses. Gene transfer models focus more directly on etiology, but require isolation of single genes, a very difficult task. Psychological process models—cross-species paradigms developed by analyzing the underlying psychological disturbance in the human illness—seem to offer the best hope at present.
TL;DR: Some of the evidence from animal and clinical studies, implicating cholecystokinin (CCK)-peptides in the pathophysiology of schizophrenia is presented, suggesting the co-existence of CCK and DA is of interest in view of the DA hypothesis of schizophrenia.
Abstract: Publisher Summary This chapter presents some of the evidence from animal and clinical studies, implicating cholecystokinin (CCK)-peptides in the pathophysiology of schizophrenia. CCK pathways are extensively distributed throughout the CNS. CCK-immunoreactivity (CCK-IR) is co-localized with dopamine (DA) in some DA neurons projecting to limbic structures. The extent of the co-localization is species dependent. The co-existence of CCK and DA is of interest in view of the DA hypothesis of schizophrenia and the putative role of limbic dysfunction in the pathophysiology of this disorder. Several biochemicals, electrophysiological, and behavioral studies point to an interaction between CCK and DA. Some studies point to an inhibitory effect of CCK peptides on DA function, which would be compatible with a potential antischizophrenic action, others point to an enhancement. CCK peptides show a neuroleptic-like profile in several screening tests for neuroleptics but not in all studies. Cerebrospinal fluid (CSF) CCK-IR is described as being unchanged or decreased in schizophrenia. Autopsy studies have shown significant decreases, increases, or no change in brain CCK-IR in schizophrenia.
TL;DR: In this article, the authors define the term "coenaesthesiopathia" to describe the feeling of fullness, accompanied by a desire to micturate, but not necessarily painful.
Abstract: Publisher Summary A common sensation can become clearly unpleasant but not necessarily painful, as in motion sickness or in the sensation of “air hunger”. This chapter discusses the term that defines this kind of unpleasant sensation, “coenaesthesiopathia”. Visceral pain can arise from a visceral common sensation—that is, sensations from the bladder. The common sensation is the feeling of fullness, accompanied by a desire to micturate. If it is inconvenient to micturate, the desire to do so becomes stronger and unpleasant, but it is still not painful. During severe urinary retention, as occurs in acute urinary bladder obstruction, this unpleasant feeling becomes increasingly painful. The most important visceral sensation is the visceral pain. The stimuli that induce pain in viscera are different from those that induce pain in the somatic structures. This explains why in the past the viscera was considered to be insensitive to pain.
TL;DR: This chapter describes mechanisms of protein kinase activation and control, which account for the observed phosphorylation of proteins before and after depolarization, and outlines the possible functions of the major synaptosomal phosphoproteins in relation to neurotransmitter release.
Abstract: Publisher Summary This chapter reviews the methods used to study synaptosomal protein phosphorylatio to evaluate the limitations of the procedures and the likelihood of introducing in vitro artefacts. It describes the major synaptosomal phosphoproteins and the effect of depolarization on their labeling with 32Pi. The chapter focuses on phosphoproteins having molecular weights between 40 and 90 kDa because these proteins have been extensively investigated in disrupted synaptic tissue. The chapter describes mechanisms of protein kinase activation and control, which account for the observed phosphorylation of proteins before and after depolarization, and outlines the possible functions of the major synaptosomal phosphoproteins in relation to neurotransmitter release. A number of experimental systems have been used to investigate the role(s) of protein phosphorylation in neurotransmitter release and, out of these, synaptosome preparations constitute an excellent model. These subcellular organelles have the particular advantage of being an in vitro nerve terminal preparation that retains the capacity to release neurotransmitters in a physiologically relevant manner. They are relatively homogeneous compared to neuronal cell cultures containing axons, cell bodies, dendrites and nuclei, and brain slices, which contain nonneuronal cells.
TL;DR: In many cases of the visceral disease pain arises from the somatic structures innervated from the same spinal segments as the troubled viscus, and this suggests that the phenomenon has a spinal mechanism.
Abstract: Publisher Summary This chapter explains the existence of the polymodal receptors in the visceral afferent type C - neurones. However, the concept of nociception is difficult to apply to the viscera; cutting, crushing, or burning the visceral tissue generally produces no pain. Excessive distension of the hollow viscera, such as the intestine or the bladder, can activate mechanoreceptors of C-fibres and evoke pain, but it is not possible to say if such stimuli are tissue-damaging. Furthermore, in many cases, this chapter discusses the visceral disease pain that arises from the existence of the polymodal receptors in the visceral afferent type C-neurones. However, the concept of nociception is difficult to apply to the viscera; cutting, crushing, or burning the visceral tissue generally produces no pain. Furthermore, in many cases of the visceral disease pain arises from the somatic structures innervated from the same spinal segments as the troubled viscus, and this suggests that the phenomenon has a spinal mechanism.
TL;DR: This chapter discusses the discharge patterns of the sympathetic pre- and post-ganglionic neurones, which are composed of reflexes that can be elicited in the neurones under standardized experimental conditions and are an important step towards the description of the different types of “final common sympathetic paths” to the target organs.
Abstract: Publisher Summary This chapter discusses the discharge patterns of the sympathetic pre- and post-ganglionic neurones The discharge patterns are composed of reflexes that can be elicited in the neurones under standardized experimental conditions Many of these reflexes and discharge patterns, probably, cannot be seen during the neuronal ongoing regulations of the target organs in unanaesthetized animals They are artificial entities that are used, by the experimenter, in the analysis and, so to speak, are the language of the neurones, by which they reveal some properties of the central organization of the systems, provided the experimenter asks reasonable questions— that is, uses meaningful and adequate stimuli The analysis of the discharge patterns of the sympathetic neurones is an important step towards: (1) the description of the different types of “final common sympathetic paths” to the target organs, (2) the recognition of the functionally different types of the preganglionic neurons in the spinal cord, and (3) the development of general ideas about the central organization of the sympathetic systems
TL;DR: The studies of the effect of stalk transections or PVN lesions on transmitter levels in the posterior pituitary have helped to show whether neurotransmitters are in non-neuronal cells intrinsic to the posterior lobe or in processes provided by neurons extrinsic to it.
Abstract: Publisher Summary This chapter focuses on magnocellular neurons There are two major groups of large neurosecretory neurons in the hypothalamus: one in the supraoptic nucleus (SON) and the other in the paraventricular nucleus (PVN) The magnocellular neurons develop from midline neuroblasts Those in the SON migrate ventrolaterally and take up residence alongside the optic chiasm The scattered nests of cells fail to complete this migration and come to rest between the PVN and SON These nests of neurons are called “accessory magnocellular cells” and make up less than 5% of the magnocellular population The chapter demonstrates the presence or absence of particular transmitters in magnocellular cells The studies of the effect of stalk transections or PVN lesions on transmitter levels in the posterior pituitary have helped to show whether neurotransmitters are in non-neuronal cells intrinsic to the posterior lobe or in processes provided by neurons extrinsic to it The various magnocellular neurons make vasopressin—the antidiuretic hormone—or oxytocin—the hormone responsible for milk letdown
TL;DR: This chapter discusses the respiratory proprioception that can be of pressure, volume, flow, ventilation or loading, elastic or resistive loads frequently being studied.
Abstract: Publisher Summary Most parts of the lungs and airways, but not the nose, are distensible and contain proprioceptors in their walls. However, distension and collapse will also affect afferent information from the surrounding somatic muscles of breathing, and the volume change may be initiated by the contraction of these muscles. Therefore, it is not always easy to determine the site of origin of the proprioceptive sensation: most analytical studies have depended on the nervous blockade by local anaesthesia or by disease. This chapter discusses the respiratory proprioception that can be of pressure, volume, flow, ventilation or loading, elastic or resistive loads frequently being studied. A mouthpiece or nose-clip is usually used, thus distorting an important part of the airway sensing system. Flow and pressure can certainly be detected in the nose and mouth, but there is little evidence for their detection more peripherally.
TL;DR: The studies have shown that NPY given intracutaneously in the α-chloralose anesthetized rat can reduce arterial blood pressure and heart rate and have been observed in the presence of α-adrenergic receptor blockade.
Abstract: Publisher Summary The morphological studies in the past have been performed by means of computer-assisted morphometry and microdensitometry to give an objective representation of the central adrenaline (A) nerve cell groups in the medulla oblongata. The functional and biochemical studies of the A neurons within the medulla oblongata, especially within the dorsal cardiovascular region, have given evidence that the adrenergic neurons have an important vasodepressor function in the central nervous system (CNS). The existence of neuropeptide Y–like immunoreactivity in the A cell groups C1, C2, and C3 in the medulla oblongata has been demonstrated by studies in the past. Based on these observations, the effects of centrally administered neuropeptide Y (NPY) on cardiovascular and respiratory parameters and on pre- and postsynaptic mechanisms in central A nerve terminal networks in the dorsal cardiovascular region of the medulla oblongata of the rat have been analyzed. These studies have shown that NPY given intracutaneously in the α-chloralose anesthetized rat can reduce arterial blood pressure and heart rate. These actions have been observed in the presence of α-adrenergic receptor blockade.