Showing papers in "Progress in Brain Research in 1983"

Morphology of vasopressin and oxytocin neurones and their central and vascular projections.

Abstract: Publisher Summary Vasopressin and oxytocin projections may be involved in the regulation of autonomic activity, and the paraventricular nuclei (PVN) sends vasopressin and oxytocin projections to various autonomic centers in the brainstem and spinal cord. This chapter discusses the immunohistochemical studies on the distribution, morphology, and projections of neurons producing classical neurohypophysial peptides and presents evidence that neurons in this system may produce additional peptides. Vasopressin and oxytocin are associated with a family of low molecular weight proteins, the neurophysins, also present in the extracts of the neurohypophysis. Vasopressin and oxytocin are present in fibres throughout the mammalian central nervous system. In target areas, fibres surround and contact neurons and in some cases these contacts have been identified as synaptic. In a number of these areas, vasopressin and oxytocin have been shown to alter the electrical or biochemical activity of neurons, and may be involved in various centrally regulated functions. There is evidence that both vasopressin and oxytocin can alter the electrical activity of neurons in various parts of the central nervous system, where fibres containing these peptides are present. Thus these peptides, which were originally characterized as the circulating hormones released from the neurohypophysis, may have an additional important role in influencing the activity of central neurons through direct projections to these neurons.

Inhibition of protease activity can lead to neurite extension in neuroblastoma cells.

Abstract: Publisher Summary Neurite extension is one of the first morphological steps in neuronal differentiation. A study on the nature and the regulation of the biochemical events involved in this phenomenon requires an appropriate experimental model. The extension of neurites in neuroblastoma cells offers a number of experimental advantages for such an approach. Glial cells, including gliomas, release a macromolecular factor that induces a dose-dependent neurite outgrowth in neuroblastoma cells. This chapter explores the possibility that inhibition of cell surface associated proteases is involved in the glia induced neurite extension in neuroblastoma cells.

The Organization and Biochemical Specificity of Afferent Projections to the Paraventricular and Supraoptic Nuclei

Abstract: Publisher Summary The paraventriculo(PVN)-supraoptico(SON)-neurohypophysial system is the most thoroughly characterized peptidergic system in the brain, both from the electrophysiological and the anatomical points of view. This chapter describes the organization of the neural inputs that relay sensory information from the periphery to the PVN and SON nuclei and presents several conclusions about the organization of central pathways, which regulate the magnocellular neurosecretory system—while many cell groups project to the PVN, relatively few provide inputs that end in the magnocellular division or in the SON, which does not contain a distinct parvocellular division. With the possible exception of a projection from the median preoptic nucleus, inputs to the magnocellular neurosecretory system end preferentially in the areas that are rich either in oxytocin- or in vasopressin-neurons. The major feature that distinguishes the PVN and SON is the association of an elaborately organized parvocellular division with the former, and recent evidence suggests that cells in the parvocellular division project to nearby magnocellular neurons. The chapter describes 10 of these neuroactive substances within cell bodies in the PVN, and there is evidence that both oxytocin and corticotropin releasing factor are found in some magnocellular neurons, while vasopressin and dynorphin are found in others. Although, the functional significance of the co-existence of peptides within neurosecretory neurons is not clear, it is tempting to speculate that inputs from different sources, which release different neuroactive substances, differentially affect the synthesis and (or) release of one or another of the peptides in a particular cell type in the PVN.

Stimulus-secretion coupling.

Abstract: Publisher Summary This chapter outlines the main findings of Ca release and buffering in neurohypophysial nerve terminals and the process of exo-endocytosis Both hormone and neurophysin are found in the granule-free supernatant of homogenized neural lobes, and a greater proportion of free hormone can be found in supernatants derived from dehydrated, hemorrhaged, and lactating rats In a variety of tissues, mitochondria have been suggested to be responsible for Ca homeostasis Neural lobes fixed in the presence of oxalate and post-fixed with OsO4, solution containing potassium antimonate show heavily stained mitochondria The mitochondria retain their precipitates after the tissue has been washed in phosphate buffer, but no deposit could be observed when the neural lobes are incubated in EGTA-containing medium before post-fixation However, how the Ca accumulated in microvesicles is released is not known A rise in cytoplasmic Ca is sufficient to promote hormone release, and depolarization is not a prerequisite for secretion Magnocellular neurons of the hypothalamus show specific patterns of electrical discharge during activities, such as suckling, hemorrhage and dehydration In isolated neural lobes stimulated electrically in a medium in which action potentials can propagate, the release of hormone is maximal at a frequency of Ca Although there has been some progress in this field during the past 20 years, there is a second, largely unknown, step of the stimulus-secretion coupling mechanism—that is, the step during which Ca promotes hormone release This is true not only for the neural lobe but also for other secretory systems

Functional Organization of the Visual Cortex

Abstract: Publisher Summary Although the cortex is in many ways a uniform structure, different regions of cortex are devoted to very different purposes, ranging from sensory perception to motor control to higher intellectual functions. Within the sensory cortex, one finds a further spatial segregation of the modalities. The focus of this chapter is the primary visual cortex, which, though only one of a number of cortical visual areas, bears many structural similarities to all other areas of cortex. Each visual area has a functional organization that follows several rules, including retinotopic order, columnar ordering of specific receptive field features and laminar segregation of functional cell types. With regard to retinotopic order, certain areas devote more space to particular parts of the visual field more than others, and some have less rigidly organized maps than others. The distribution of the cortical afferents, the intrinsic connections of the cortex, and the pattern of connections between cortical areas are also described in this chapter.

Regulation of Vasopressin Release by Neurotransmitters, Neuropeptides and Osmotic Stimuli

Abstract: Publisher Summary This chapter discusses the regulation of vasopressin (AVP) release from the neurohypophysis and the known effects of afferents to the supraoptic nucleus (SON). The signals regulating AVP release from the neurohypophysis for the maintenance of these functions involve osmoreceptive mechanisms located primarily in the hypothalamus and signals relayed from the cardiovascular volume and baroreceptors. AVP release is also altered by the changes in emotional states, pain, exercise, and the act of drinking. The AVP neurone itself is osmosensitive, in which increases in the osmolarity of the extracellular fluid cause depolarization of the membrane and a resulting sensitization of the neurone to other excitatory inputs. However, this inherent osmosensitivity is inadequate to generate firing of the neurone and subsequent AVP release by itself. The ability of osmotic stimulation to override noradrenergic inhibition emphasizes the prominent role of the osmotic control of AVP release and is consistent with the postulated role for the noradrenergic innervation in conveying signals from the cardiovascular baro- and volume-receptors. The interaction between noradrenaline and osmotic stimulation in determining AVP release would fit with a role for noradrenaline in transmitting cardiovascular information as the osmotic regulatory mechanisms can override the effects of noradrenaline. However, the information conveyed by the other chemically identified afferents to the SON remain to be established, and the mechanisms, which integrate all of these signals to achieve a rate of hormone release appropriate to the physiological circumstances, remain to be elucidated.

Polyribosomes associated with dendritic spines in the denervated dentate gyrus: evidence for local regulation of protein synthesis during reinnervation.

Abstract: Publisher Summary Evidence has been steadily accumulating in recent years that neurons of the mature mammalian central nervous system can dramatically remodel their synaptic connections either in response to denervating lesions or in response to patterns of activity. Many of these observations of neuronal “plasticity” have involved the dendritic spine, where neurons of the mammalian brain, particularly cortical neurons, receive the majority of their excitatory synaptic inputs. Numerous studies have demonstrated alterations in spine size or number in response to denervation and reinnervation, and in response to alterations in afferent activity. The malleability of spines is somewhat difficult to reconcile with classical notions of neuronal cell biology. A major tenet of cellular neurobiology is that the major synthetic activity of the neuron occurs in the cell body. Accordingly, the construction and maintenance of the detailed morphological specializations of the neuron (including the spine and associated postsynaptic membrane specialization) are thought to depend on the specific transport of already synthesized material from the cell body. This chapter summarizes the observations on the changes in the incidence of polyribosomes associated with dendritic spines during post-lesion reinnervation of the dentate granule cells.

Central actions of neurohypophysial hormones.

Abstract: Publisher Summary Nurohypophysial hormones are involved in the learning and memory processes, and several approaches have been used to determine the physiological significance of the neurohypophysial hormones in the memory processes. This chapter describes the various approaches that have been used to determine the physiological significance of the neurohypophysial hormones in the memory processes. Different approaches include animals with a vasopressin deficiency as induced by the removal of the neurointermediate lobe of the pituitary, rats of the Brattleboro strain that have a genetic disturbance in the synthesis of vasopressin, and rats with a temporary deficit in brain vasopressin produced by i.c.v. injection of specific vasopressin antiserum. Vasopressin facilitates memory consolidation and retrieval, while oxytocin may be regarded as an amnesic neuropeptide. The central nervous system (CNS) effects of these hormones are of central origin, as appeared from lesion studies, experiments in diabetes insipidus rats, studies from i.c.v. administered peptides and specific antisera particularly the brain areas, and studies on the vasopressin levels in blood and cerebrospinal fluid (CSF) during memory consolidation and retrieval. Neurochemical experiments suggest that the memory effects of the neurohypophysial hormones are mediated by modulation of catecholamine transmission in restricted areas in the brain. The neurohypophysial hormones have a variety of CNS effects—they modulate drug-seeking behavior, electrical self-stimulation, and tolerance development to and physical dependence on opiates. Other effects of vasopressin include temperature regulation, cardiovascular control, and brain development.

An outlying visual area in the cerebral cortex of the cat.

Abstract: Publisher Summary The visual cortex has been shown in both primates and non-primates to include a large number of extrastriate areas in addition to the classically defined visual areas 17, 18 and 19. Not all of these extrastriate areas contain full representations of the visual field, but, whether their maps are partial or complete, the areas abut one another, often with mirror reversals at their borders. As a consequence, the striate and extrastriate areas together form a zone of exclusive visual reponsiveness in the posterior neocortex that is continuous even though having separate areas within it. The arrangement of these visual areas into a continuum has obvious advantages in keeping transcortical association pathways short and also has suggested that the multiple maps might have evolved by a process akin to gene duplication. A visual area has been recently discovered, which appears anomalous in that it lies at a distance from the striate and extrastriate areas, in the anterior part of the cat's cerebral cortex, and yet, like the posterior visual areas, is a zone containing unimodal visually responsive neurons.

Neurohypophysial Peptides in Cerebrospinal Fluid

Abstract: Publisher Summary The neurohypophysial peptides in cerebrospinal fluid (CSF) are believed to function as neurotransmitters or neuromodulators within the central nervous system (CNS). This chapter describes the neurohypophysial peptides and their actions on the CNS,often following administration of exogenous peptides or their antisera into CSF. Oxytocin (OXT), vasopressin (AVP), and neurophysin (NP) are found in many areas of the brain and spinal cord. Because, there is a blood–CSF barrier to these peptides, CSF levels probably reflect release from central terminals rather than the hypothalamo–neurohypophysial system. The physiological stimuli, which release these peptides into CSF, are poorly understood. Endocrine stimuli (suckling, dehydration) causing release into plasma do not change CSF levels of OXT, AVP, or NP, but central release of AVP occurs during hemorrhage. Electrical stimulation of the hypothalamus releases all three peptides into CSF and perfusates of different parts of the ventricular system. There is a marked diurnal rhythm of AVP in CSF and a large molar excess of NP over the nonapeptides. Although OXT and AVP are cleared somewhat faster than NP, this cannot explain the NP excess, which is mostly due to the OXT-related protein. Much of the AVP cleared from CSF reaches the bloodstream in a biologically active form, and it now seems likely that central OXT and AVP neurons are both morphologically and functionally separate from the neurohypophysial system. CSF measurements, thus, provide a useful, though indirect, means of studying these peptides within the central nervous system.

Control of the optokinetic reflex by the nucleus of the optic tract in primates.

Abstract: Physiological and anatomical experiments clearly established the existence of a pretectal relay of visual information to the ipsilateral inferior olive in the macaque monkey. Horseradish peroxidase injected into the inferior olivary nucleus retrogradely labelled neurons in the nucleus of the optic tract (NOT) and the dorsal terminal nucleus of the accessory optic tract (DTN). The response characteristics of NOT-DTN neurones are described in this chapter. The visual receptive fields of neurones in NOT and DTN in anaesthetized and paralysed macaque monkeys prefer horizontal ipsiversive movements of single objects or whole field random dot patterns, i.e. neurones in the left NOT-DTN prefer leftward movements and vice versa. The directional tuning widths of NOT-DTN neurones are very broad. Directions withing a mean range of 127 +/- 25 degrees visual angle elicit response strengths greater than 50% of the maximal response. Visual latencies to reversals in directions of stimulus movement are in a range from 40 to 80 ms (mean 61 +/- 13 ms). Combining two visual stimuli by moving a random dot pattern and a single bar of light simultaneously but in opposite directions causes NOT-DTN neurones to respond to each stimulus as soon as it moves in the cell's preferred direction. The reduced overall response strengths indicate additional inhibitory interactions. All NOT-DTN neurones can be activated from each eye. Interactions between the two eyes are modest and unspecific. Optical speeds of stimulus movement vary for different NOT-DTN neurones (4-60 deg/s). The effective range of speeds is broad (0.1-400 deg/s for the total population). With oscillating horizontal stimulation NOT-DTN neurones follow repetition rates up to 4 Hz. Receptive fields are mostly large (20-40 degrees visual angle), include the fovea, and extend up to 20 degrees into the ipsilateral hemifield. The sensitivity to moving stimuli is highest near the fovea. Our results thus indicate that direction selective cells in the NOT and DTN have all the properties and connections which are necessary and sufficient to control the stability of the image on the retina by supplying retinal slip information to the velocity storage integrator in the brainstem (Raphan et al., 1979).

Elimination of synapses during the development of the central nervous system.

Abstract: Publisher Summary During the development of the nervous system, after the setting out of neuronal somas, the growth of their processes (axons and dendrites) leads to the formation of a network of synaptic connections that in the adult exhibits both precision and diversity. Synaptic contacts are generally established between partners belonging to well-defined and homogeneous categories of cells. These classes of synapses represent a first level of order within the system; the specificity of recognition between appropriate classes of cell is strict but probably not absolute: functional “heterologous synapses” might be formed between cells which, under normal conditions, never form synapses. The accuracy of synaptic connections within a given class of synapses represents another level of complexity. Without doubt, the connections between subsets of neurons are very precisely established, although it is not clear to what extent the connections have to be precise to generate a given behavior. Several mechanisms have been proposed for the creation of such order and diversity but many of them are not mutually exclusive, because the acquisition of such a synaptic accuracy is likely to be not a single step process but a progressive and sequential one.

The organum vasculosum laminae terminalis: a critical area for osmoreception.

Abstract: Publisher Summary The volume and composition of the body fluids is maintained by coordinated control of water intake by thirst mechanisms and water output via vasopressin secretion. This chapter describes and presents evidence in favor of the organum vasculosum laminae terminalis (OVLT) as site of osmoreception (both osmotic and volaemic regulation of water balance). Evidence presented in the chapter demonstrates that the osmoreceptors behave as if they were located in an area of the brain lacking the blood-brain barrier and that this area is likely to be in the anterior hypothalamus. Although, there is electrophysiological evidence that cells elsewhere in the brain, such as the supraoptic nucleus, show osmosensitivity, their capacity to respond to reasonable osmotic challenges is in question. Animals with discrete lesions of the OVLT have greatly diminished responses to osmotic stimuli and abolition of these responses over reasonable physiological range, whereas the identity of the osmoreceptors remains elusive; their anatomical home, the OVLT, is more certain.

Compartmental Organization of the Mammalian Striatum

Abstract: Publisher Summary By far the most striking architectural characteristic of the mammalian cerebral hemisphere is its division into tissue of cortical and subcortical types. This distinction has dominated views about the level of sophistication and neural processing in different parts of the telencephalon, and has also influenced ideas about the evolution of the cerebral hemispheres from an apparently more primitive striatal type to the exquisitely differentiated neocortical type found in higher mammals, especially man (Herrick, 1926, 1956; Romer, 1962). Because the cerebral cortex is the largest subdivision of the human brain, and disproportionately so by comparison with other species, the view naturally arose that the specialized structure of cortex somehow forms a necessary prerequisite for the complex mental capacities unique to the human. The fact that there is very little cortical tissue in the telencephalon of non-mammalian vertebrates, but instead a large noncortical “striatal” mass, led to the parallel assumption that the striatum is the highest integrative subdivision in these forms. Thus for years it was thought that the great development of the striatum in birds was related to their highly evolved instinctive patterns of behavior. This chapter focuses on compartmental organization of the mammalian striatum.

Vasopressin: mechanisms of receptor activation.

Abstract: Publisher Summary Vasopressin exerts a large variety of biological effects such as increased glycogenolysis and neoglucogenesis by liver cells and increased corticotrophin release by the adenohypophysis. This chapter presents an overview of the available pharmacological and biochemical data on vasopressin receptors in mammals. The chapter discusses those receptors for which binding data are presently available. Vasopressin receptors have been characterized on renal membranes from several mammalian species and on two extrarenal vasopressin-sensitive cell types in the rat—namely, isolated hepatocytes and aortic smooth muscle cells in primary culture. Renal and extrarenal vasopressin receptors have similar hydrodynamic properties; however, they can be distinguished on the following grounds—(1) renal vasopressin receptors are coupled to adenylate cyclase, (2) kidney and liver vasopressin receptors are affected by triphosphonucleotides, and (3) hepatic and aortic vasopressin receptors in the rat have almost identical recognition patterns. In all vasopressin-sensitive cells tested so far, the dissociation constant for vasopressin binding to the receptors is much higher than the hormonal concentration eliciting half-maximal biological response. This suggests that a marked amplification occurs at steps beyond adenylate cyclase activation or activation of the primary effector involved in calcium mobilization.

Vasopressin-like Peptides and the Treatment of Memory Disorders in Man

Abstract: Publisher Summary Peptides related to vasopressin and oxytocin affect animal behavior in a number of different test situations, and these peptides are involved in the memory processes and learning. This chapter describes the memory disorders and discusses clinical studies and relevant aspects of the neuropsychology of memory disorders with emphasis to the pharmacological methods used to study treatment effects, with the use of lysine-vasopressin (LVP), arginine-vasopressin (AVP), des-glycinamide-arginine-vasopressin (DGAVP), or 1-desamino-D-arginine-vasopressin (DDAVP). These peptides have behavioral effects in humans based upon the fact that most studies find something, whether it is a clinical impression of improvement or objective test results. The amount of active principle that can be used in humans is limited, due to peripheral side-effects, while high doses are necessary to enable sufficient vasopressin to pass the blood–brain barrier and reach the CNS. Another important methodological point concerns the nature of the active principle to be used; DGAVP is favored above DDAVP, especially LVP, because it lacks the peripheral endocrine effects, which occur with AVP/LVP and partly with DDAVP. The conclusions that can be drawn from the clinical studies performed to date are in line with those based upon animal experiments. However, future patient studies may yield more relevant information, when they make more use of the extensive knowledge collected for the past decade in animal experiments.

Ultrastructural manifestations of increased hormone release in the neurohypophysis.

Abstract: Publisher Summary This chapter focuses on the ultrastructural changes that accompany altered hormone release, with current opinions and speculation about the role of the anatomical elements during hormone release. The anatomical elements of the neural lobe show a good deal of change during increased hormone release. The dense core vesicles of the axon terminals can be depleted and those in the axon swelling eventually recruited. Intra-axonal lysosomes increase, smooth endoplasmic reticulum proliferates, and microvesicles re-distribute. The pituicyte processes withdraw from the basement membrane, possibly to provide a greater surface area for hormone release. Pituicytes also unwrap from around axonal processes, probably freeing axon terminals. Blood vessels dilate, filling up more of the perivascular space. All of the classifiable components of the neural lobe show ultrastructural changes during increased hormone release. Studies of the median eminence and magnocellular cell bodies of the hypothalamus suggest that the anatomical flexibility seen in the neural lobe may exist in these regions as well.

Age-Dependent Paralytic Viral Infection in C58 Mice: Possible Implications in Human Neurologic Disease

Abstract: Publisher Summary This chapter analyzes the specific ways that aging, viral infection, genetic factors, and immune deficiency act together to predispose mice to paralytic disease using an age-dependent motor neuron disease in C58 mice as an experimental model. Lactic dehydrogenase virus (LDV) is widespread in both domestic and wild mice and causes life-long infection. Immune complexes typically are found in the plasma of infected mice. LDV does not cause significant pathologic changes in the tissues of infected mice under ordinary circumstances. The properties of LDV are summarized in the chapter. LDV derived from line Ib transplantable leukemia causes a fatal inflammatory motor neuron disease when inoculated into C58 mice that are 9 or more month of age, and in younger C58 mice, providing that they are immunosuppressed first by X-irradiation or drugs. LDV strains differ markedly in their neuropathogenicity ranging from those that are highly paralytic to those that cause inapparent infection.

Precursors of Vasopressin and Oxytocin

Abstract: Publisher Summary It is now known that in addition to transcription and translation processes, various signal sequences and post-translational processing events are also involved in determining the type of peptides that are secreted by the cell. This chapter describes unequivocal criteria for the identification of precursors of peptides with regard to both vasopressin and oxytocin. These criteria include (1) demonstration in classical pulse-chase experiments in intact cellular systems that a larger form of the peptide is first synthesized and subsequently decreases in radioactivity as the radioactive peptide is formed, (2) demonstration by in vitro translation experiments that a larger precursor form of the peptide is synthesized, and (3) utilizing modem recombinant DNA techniques to clone cyclic DNA (cDNA) obtained from a purified messenger RNA (mRNA) template using reverse transcriptase. A variety of biosynthesis studies conducted in vivo and in vitro have shown that the vasopressin precursor is a 19–23,000 molecular weight glycoprotein, which contains vasopressin at its N-terminus, neurophysin in the middle, and a 39 amino acid glycopeptide at the C-terminus. While, the 15–16,000 molecular weight oxytocin precursor is not glycosylated. The vasopressin precursor has been completely sequenced by recombinant DNA methods, thereby providing insights into the nature of the glycopeptide as well as post-translational processing mechanisms. However, many questions remain to be answered such as the nature of the post-translational processing enzymes and mechanisms that fashion the final peptide products or the mechanisms underlying the transcriptional and translational regulation of the precursors during functional activity.

Presynaptic Interactions in the Neurohypophysis: Endogenous Modulators of Release

Abstract: Publisher Summary This chapter describes (1) the existence, within the neural lobe, or access to the neural lobe of endogenous substances; (2) evidence of release upon appropriate stimulation; (3) the presence of receptors; (4) pharmacological studies demonstrating influences on release of arginine-vasopressin (AVP) or oxytocin, and (5) studies demonstrating altered release during physiological or experimental stimulation. The neurohypophysis contains many substances in addition to AVP and oxytocin. These may be present in the same cells as the neurohypophysial peptides or in independent neural systems. For some of these substances, evidence is accumulating that they may be released under physiological or experimental conditions and may modulate the release of AVP or oxytocin. Whether this interaction occurs via a presynaptic receptor on the neurohypophysial axon or involves the intervention of non-neural elements in the neurohypophysis is not known. The electrical activity in neurohypophysial axons and the release of peptide may also be influenced by the ionic milieu resulting from previous activity or by circulating substances that pass through the fenestrated capillaries into the neural lobe. However, why the brain has developed a mechanism for presynaptic regulation of transmitter release that requires generation and transmission of action potentials, which will not release hormones, is a question left unanswered.

Evidence that Dopamine is a Neurotransmitter in the Neurointermediate Lobe of the Hypophysis

Abstract: Publisher Summary This chapter discusses and provides the evidence available to permit dopamine (DA) to be defined as a neurotransmitter substance in the neural and intermediate lobes (NIL) of the pituitary gland. The chapter also describes some important criteria regarded essential for any substance to be classified as a neurotransmitter, including the criterion of presence of the transmitter in the tissue; the criterion of identical actions in which the response to the putative neurotransmitter when applied to the tissue must be the same as that resulting from activation of the nerve fibres that contain it; and the criterion of collectability of the transmitter. The results have shown that DA is released in the NIL by propagated action potentials induced by electrical stimulation of the pituitary stalk, that the released DA is inactivated by monoamine oxidase (MAO), and that there is a DA re-uptake mechanism in the NIL, which contributes to the inactivation of the released DA. It has also been shown that DA synthesis occurs in the isolated NIL and that the rate of synthesis may be related to the degree of activation of the neurons. These findings, taken together with the neurophysiological and neuroendocrinological observations, provide convincing evidence that DA is a neurotransmitter substance in the NIL of the pituitary gland.

Geniculo-cortical connections in primates: normal and experimentally altered development.

Abstract: Publisher Summary This chapter emphasizes on the emergence of afferent connections from the dorsal lateral geniculate nucleus (LGd) of the thalamus to the primary visual cortex (area 17) in the cerebrum of fetal rhesus monkeys. Author started this series of studies with the hope that it would enhance the understanding of normal and pathological development in the human visual system and perhaps elucidate indirectly the pathogenesis of various congenital disorders of the cerebral cortex. The developing visual cortex seems to be a reasonable experimental model for that purpose because its cellular organization and characteristics of binocular and color vision are remarkably similar in both monkeys and man. The chapter is concerned with the basic anatomical organization of geniculo-cortical input in the adult monkey. Later it deals with critical developmental events and prenatal mechanisms that may be at play during the genesis of the normal pattern of geniculo-cortical connections in primates. Finally, the morphological consequences of selective prenatal destruction of eye(s) that affect secondarily the development of central visual pathways are used as a criterion for determining the extent of capacity for synaptic reorganization within the primate visual cortex.

In Vitro and In Vivo Effects of β-Endorphin and Met-Enkephalin on Leukocyte Locomotion

Abstract: Publisher Summary Several peptides have been described with chemotactic activity for neutrophils and monocytes The one most widely studied has been formyl methionyl leucyl phenylalanine (f-MLP) This peptide is a potent chemotactic factor for both monocytes and neutrophils, and recent studies have demonstrated the presence of specific receptors for these peptides on human neutrophils, and monocytes Although these peptides are potent chemotactic factors, there is no evidence that they are naturally produced by the host, although the production of similar agents by bacteria has been described Recently the hypotensive, vasodilator and smooth muscle contracting peptide, substance P has been shown to stimulate rabbit neutrophil chemotaxis and lysosomal enzyme release This neuropeptide also blocks the binding of f-MLP to its receptor, and, therefore, may act through this receptor Substance P has also been associated with pain transmission Other nervous system-produced peptides, such as amino and carboxyterminal substituent tetrapeptides of angiotension, have been shown to be chemotactic for human monocytes, with lesser activity for neutrophils Other studies have shown that human mononuclear phagocytes specifically bind [1125]8-L-arginine-vasopressin, and that vasoactive intestinal polypeptides can be found in polymorphonuclear leukocytes All of these studies indicate that cells of the immune system may be directly affected by products of the central nervous system As immigration of leukocytes to a site of inflammation is a primary step in host defense, it is the purpose of this study to determine if P-endorphin or the 5 amino acid constituent of P-endorphin, Met-enkephalin, have any effect on monocyte, lymphocyte or neutrophil locomotor responses

Organization of Neural Inputs to the Supraoptic and Paraventricular Nuclei: Anatomical Aspects

Abstract: Publisher Summary This chapter presents an overview of recent contributions of anatomical studies to the understanding of the afferent control of oxytocin and vasopressin secretion and outlines the problems of interpretation and areas of expanding interest. Cytochemical techniques make structural studies important also in the analysis of neurotransmitters in those systems. Ideally, such analyses should provide a circuitry that explains the coupling between effective stimuli and the release of hormone, including the coordinated multicellular release of oxytocin in milk ejection. While most SON neurons project to the neurohypophysis, many neurons of the PVN (especially its parvocelhlar portion) project to other parts of the central nervous system, in some cases to the sites from which afferent inputs are derived. Many PVN neurons are neither oxytocinergic nor vasopressinergic, making the demonstration that an afferent system ends within the nucleus insufficient to permit a precise functional interpretation. Immediate afferents to the magnocellular neurons arise from both long projection systems and local interneurons. They form synapses on dendrites, somata, and axons and may also influence the neurons by non-synaptic release of transmitter in the hypothalamus or actions on the neurohypophysial neurosecretory terminals.

The Identification and Role of Cells Involved in CNS Demyelination in Mice After Semliki Forest Virus Infection: An Ultrastructural Study

Abstract: Publisher Summary This chapter describes the mechanisms involved in the demyelinating process, focusing on the electromicroscopical identification and role of the cells that are present at the demyelinating sites. The chapter puts forward a hypothesis to explain the method of formation of the spongiform (microcystic) changes that occur, and the significance of these in relation to the demyelination seen. Cell-mediated immune system plays the most important role in the pathological process, including the demyelination. In SFV infections of athymic nude mice, minimum demyelination occurs within the first 28 days after infection, suggesting that the demyelination is T-cell-dependent. Demyelination is reproduced if these mice are reconstituted with normal spleen cells before virus infection. Reconstitution studies at present being carried out suggest that, if the spleen cells used for reconstitution are depleted of T-cells, the demyelination is significantly reduced. The lymphoblastic cells appear to be very similar to the activated T-lymphocytes (lymphoblasts). It is possible that these highly mobile cells produce damage when they make close contact with the myelin possibly by the secretion of some cytotoxic substances. These may damage the myelin, making it more permeable to ions and thereby causing osmotic imbalance and cystic developments within it, with eventual rupture. As projections from these lymphoblastic cells were not seen penetrating the myelin, it would seem that direct cell insertion is unlikely to be the cause of myelin breakdown.

Design of potent and selective in vivo antagonists of the neurohypophysial peptides.

Abstract: Publisher Summary This chapter discusses the design and synthesis of potent and selectively acting agonistic analogs of oxytocin and vasopressin and some of their uses All the reported oxytocin and vasopressor antagonists antagonize both uterine and vascular responses to oxytocin and vasopressin (AVP), and all the known antidiuretic antagonists also antagonize vasopressor responses to AVP and oxytocic responses to oxytocin However, many of the more recent antagonists in each category exhibit considerably enhanced selectivities with respect to their antagonistic potencies at uterine, vascular, and renal tubular receptors The approach to antagonist design relies heavily on (1) the wealth of structure-activity data on oxytocin and AVP analogs and structure-activity data on analogs of other peptides and (2) judicious application of the additivity principle—that is, combining in a single molecule those individual modifications However, all of the antagonists developed to date lack absolute specificity Certainly for pharmacological and receptor studies, highly selective antagonists are of much greater value than multiple site antagonists Thus, the search for potent and selective antagonists in each category must continue in the hope of attaining therapeutically useful antagonists devoid of possible unwanted side-effects and which, in addition, might be active following oral administration The elucidation of new roles for oxytocin and vasopressin in other tissues, for example, brain, may endow these and future antagonists with significance and uses far beyond any present day expectations

The Topographical Distribution of the Monoaminergic Innervation in the Basal Ganglia of the Human Brain

Abstract: Publisher Summary Biochemical studies on post-mortem human brain material are fraught with many difficulties and limiting factors including age of the patient, disease state, immediate pre-mortem status and time elapsed between death and freezing of the brain. A largely neglected factor in human brain studies is the possible occurrence of a regionally uneven distribution of neurotransmitters within an individual brain nucleus. In the basal ganglia complex conspicuous changes in neurotransmitter levels have been observed in several neuropsychiatric diseases. Within this complex the striatum comprises a large subcortical mass and receives its main afferents from the cerebral cortex, thalamus, substantia nigra and dorsal raphe nucleus. There is increasing neurochemical evidence of inhomogeneities in the distribution of various neurotransmitter systems in the striatum of various species. The purpose of this chapter is to determine, in the normal human brain, the biochemical distribution pattern of the known monoaminergic aff erents (dopaminergic, noradrenergic, serotonergic) to the various nuclei of the basal ganglia complex.

Vasopressin vascular and reflex effects--a theoretical analysis.

Abstract: Publisher Summary This chapter describes the role of vasopressin (AVP) in cardiovascular function and presents evidence for the (1) participation of AVP in the short-term regulation of arterial pressure by its direct vascular actions and (2) AVP interaction with the central nervous system baroreceptor reflex pathways. The chapter suggests that most of the arterial pressure regulation with AVP infusion can be explained by reflex control of venous compliance or unstressed volume. The extent to which cardiac output is altered by AVP is dependent on the relative degree of arterial vasoconstriction between the compliant and non-compliant parallel flow beds. However, not all of the observed actions of AVP are accounted for, particularly, the predicted rise in total peripheral resistance (TPR) is less than that seen in normal animals with comparable AVP concentrations. It appears that some mechanism exists, whereby the reflex buffering of arterial resistance with AVP infusion is attenuated so that TPR rises to a higher level than would be predicted if the baroreceptors are attempting to offset the rise in resistance. While, equations are found, which could predict such behavior, they differ significantly from the classical single set point control theory and go beyond the present understanding of the autonomic nervous system.

Mosaics and territories of cat retinal ganglion cells.

Abstract: Publisher Summary When nerve cells have to overlay a planar surface with their dendrites so that every point is covered by at least one dendritic field, there are more or less economic ways to design such a cell assembly If the cells would be arrayed in a precisely square or hexagonal (Fig 1B) array with a minimal intercell spacing “a”, circular dendritic fields of radius “ ” or “ ” respectively would provide an at least one-fold coverage If the cells would be distributed randomly, the one-fold coverage could be either achieved by rather large dendritic fields of uniform size or by an interaction between neighboring cells, which adjust the dendritic field size to the local intercell spacing Two-dimensional sheets of neurons are not only found in the retina; arrangement in layers is common in many parts of the central nervous system The multilamellar structure of the cerebral cortex is an example and it would be interesting to see whether identical functional units there exhibit the same kinds of territorial attributes and regular intercell spacings