Action,time and the basal ganglia

The ability to control the speed of movement is compromised in neurological disorders involving the basal ganglia, a set of subcortical cerebral nuclei that receive prominent dopaminergic projections from the midbrain. For example, bradykinesia, slowness of movement, is a major symptom of Parkinson''s disease, whereas rapid tics are observed in patients with Tourette syndrome. Recent experimental work has also implicated dopamine (DA) and the basal ganglia in action timing. Here, I advance the hypothesis that the basal ganglia control the rate of change in kinaesthetic perceptual variables. In particular, the sensorimotor cortico-basal ganglia network implements a feedback circuit for the control of movement velocity. By modulating activity in this network, DA can change the gain of velocity reference signals. The lack of DA thus reduces the output of the velocity control system which specifies the rate of change in body configurations, slowing the transition from one body configuration to another.     

Basal metabolic rate and autonomic nervous system dysfunction in men with spinal cord injury

Objectives: The purpose of this study was to determine the relationship between autonomic nervous system dysfunction and basal metabolic rate (BMR), and the effect of spasticity on basal metabolic rate. Research Method and Procedures: Twenty men (11 paraplegic and 9 tetraplegic) with American Spinal Injury Association (ASIA)‐A and ‐B grade chronic spinal cord injury (SCI) participated in this study. Total body fat mass and lean tissue mass were measured in all participants using DXA by standard methods. Patients were allocated into 2 groups to determine the effect of autonomic nervous system dysfunction on BMR: Group I (T6 and upper‐level injuries with history of autonomic dysreflexia) and Group II (T7 and lower‐level injuries without history of autonomic dysreflexia). Measurements of BMR were determined by indirect calorimetry under standardized conditions. Results: There were 13 patients in Group I and 7 patients in Group II and the difference between these two in terms of time since injury, BMI, age, weight, lean tissue mass, BMR, and BMR/kg were not significant. Conclusion: We concluded that autonomic nervous system dysfunction does not affect BMR, and it might be ignored in considering energy needs in spinal cord injury.     

The placebo effect and the autonomic nervous system: evidence for an intimate relationship

For many subjectively experienced outcomes, such as pain and depression, rather large placebo effects have been reported. However, there is increasing evidence that placebo interventions also affect end-organ functions regulated by the autonomic nervous system (ANS). After discussing three psychological models for autonomic placebo effects, this article provides an anatomical framework of the autonomic system and then critically reviews the relevant placebo studies in the field, thereby focusing on gastrointestinal, cardiovascular and pulmonary functions. The findings indicate that several autonomic organ functions can indeed be altered by verbal suggestions delivered during placebo and nocebo interventions. In addition, three experimental studies provide evidence for organ-specific effects, in agreement with the current knowledge on the central control of the ANS. It is suggested that the placebo effects on autonomic organ functions are best explained by the model of 'implicit affordance', which assumes that placebo effects are dependent on 'lived experience' rather than on the conscious representation of expected outcomes. Nevertheless, more studies will be needed to further elucidate psychological and neurobiological pathways involved in autonomic placebo effects.     

Limited regulation of somatodendritic dopamine release by voltage-sensitive Ca channels contrasted with strong regulation of axonal dopamine release

The mechanism underlying somatodendritic release of dopamine (DA) appears to differ from that of axon-terminal release. Specifically, somatodendritic DA release in the substantia nigra pars compacta (SNc) persists in low extracellular Ca2+ concentrations that are insufficient to support axonal release in striatum, suggesting that limited Ca2+ entry is necessary to trigger somatodendritic release. Here, we compared the role of voltage-dependent Ca2+ channels in mediating DA release in striatum versus SNc using specific blockers of N-, P/Q-, T-, R- and L-type Ca2+ channels individually and in combination. Release of DA evoked by a single stimulus pulse in the dorsal striatum and SNc of guinea-pig brain slices was monitored in real time using carbon-fiber microelectrodes with fast-scan cyclic voltammetry. Single-pulse evoked DA release was shown to be independent of regulation by concurrently released glutamate or GABA acting at ionotropic receptors in both regions. Under these conditions, striatal DA release was completely prevented by an N-type channel blocker, omega-conotoxin GVIA (100 nm), and was decreased by 75% by the P/Q-type channel blocker omega-agatoxin IVA (200 nm). Blockade of T-type channels with Ni2+ (100 microm) or R-type channels with SNX-482 (100 nm) decreased axonal release in striatum by 25%, whereas inhibition of L-type channels with nifedipine (20 microm) had no effect. By contrast, none of these Ca2+-channel blockers altered the amplitude of somatodendritic DA release in the SNc. Even a cocktail of all blockers tested did not alter release-signal amplitude in the SNc, although the duration of the release response was curtailed. The limited involvement of voltage-dependent Ca2+ channels in somatodendritic DA release provides further evidence that minimal Ca2+ entry is required to trigger the release process, compared with that required for axon-terminal release.     

Causal interactions between the cerebral cortex and the autonomic nervous system

Mental states such as stress and anxiety can cause heart disease.On the other hand,meditation can improve cardiac performance.In this study,the heart rate variability,directed transfer function and corrected conditional entropy were used to investigate the effects of mental tasks on cardiac performance,and the functional coupling between the cerebral cortex and the heart.When subjects tried to decrease their heart rate by volition,the sympathetic nervous system was inhibited and the heart rate decreased.When subjects tried to increase their heart rate by volition,the parasympathetic nervous system was inhibited and the sympathetic nervous system was stimulated,and the heart rate increased.When autonomic nervous system activity was regulated by mental tasks,the information flow from the post-central areas to the pre-central areas of the cerebral cortex increased,and there was greater coupling between the brain and the heart.Use of directed transfer function and corrected conditional entropy techniques enabled analysis of electroencephalographic recordings,and of the information flow causing functional coupling between the brain and the heart.     

Central nervous system involvement in the autonomic responses to psychological distress

Psychological distress can trigger acute coronary syndromes and sudden cardiac death in vulnerable patients. The primary pathophysiological mechanism that plays a role in stress-induced cardiac events involves the autonomic nervous system, particularly disproportional sympathetic activation and parasympathetic withdrawal. This article describes the relation between psychological distress and autonomic nervous system function, with a focus on subsequent adverse cardiovascular outcomes. The role of the central nervous system in these associations is addressed, and a systematic review is presented of studies examining the association between stress-induced central nervous system responses measured by neuroimaging techniques and autonomic nervous system activation. Results of the systematic review indicate that the primary brain areas involved in the autonomic component of the brain-heart association are the insula, medial prefrontal cortex, and cerebellum (based on 121 participants across three studies that fitted the inclusion criteria). Other areas involved in stress-induced autonomic modulation are the (anterior) cingulate cortex, parietal cortex, somatomotor cortex/precentral gyrus, and temporal cortex. The interaction between central and autonomic nervous system responses may have implications for further investigations of the brain-heart associations and mechanisms by which acute and chronic psychological distress increase the risk of myocardial infarction, cardiac arrhythmias, and sudden cardiac death.     

Manganese exposure is cytotoxic and alters dopaminergic and GABAergic neurons within the basal ganglia

Manganese is an essential nutrient, integral to proper metabolism of amino acids, proteins and lipids. Excessive environmental exposure to manganese can produce extrapyramidal symptoms similar to those observed in Parkinson's disease (PD). We used in vivo and in vitro models to examine cellular and circuitry alterations induced by manganese exposure. Primary mesencephalic cultures were treated with 10–800 μM manganese chloride which resulted in dramatic changes in the neuronal cytoskeleton even at subtoxic concentrations. Using cultures from mice with red fluorescent protein driven by the tyrosine hydroxylase (TH) promoter, we found that dopaminergic neurons were more susceptible to manganese toxicity. To understand the vulnerability of dopaminergic cells to chronic manganese exposure, mice were given i.p. injections of MnCl₂ for 30 days. We observed a 20% reduction in TH-positive neurons in the substantia nigra pars compacta (SNpc) following manganese treatment. Quantification of Nissl bodies revealed a widespread reduction in SNpc cell numbers. Other areas of the basal ganglia were also altered by manganese as evidenced by the loss of glutamic acid decarboxylase 67 in the striatum. These studies suggest that acute manganese exposure induces cytoskeletal dysfunction prior to degeneration and that chronic manganese exposure results in neurochemical dysfunction with overlapping features to PD.     

Ingestion of coffee polyphenols suppresses deterioration of skin barrier function after barrier disruption,concomitant with the modulation of autonomic nervous system activity in healthy subjects

The aim of this study was to evaluate the effect of consumption of coffee polyphenols (CPPs) on the autonomic nervous system activity and decreased skin barrier function caused by sodium dodecyl sulfate (SDS) treatment. In this single-blind, placebo-controlled study, ten healthy male subjects consumed either a beverage containing CPPs or a placebo beverage for four weeks. CPPs significantly suppressed the deterioration in skin barrier function and skin moisture content induced by SDS treatment after the third week. Furthermore, in the heart rate variability analysis, CPPs significantly produced an increase in parasympathetic nervous activity, and a decrease in sympathetic nervous activity after the four weeks of beverage consumption. These results suggest that CPPs might influence the regulation of the autonomic nervous system and contribute to the suppressive effect on deterioration of skin barrier function.     

Infant botulism intoxication and autonomic nervous system dysfunction

Three infants presenting with severe cases of infantile botulism, occurring at 17, 30, and 180 days of life, respectively, are described in this report. All three infants presented with areflexive flaccid coma or apnoeas requiring prolonged ventilation. In serum, type B botulinum neurotoxin (BoNT/B) was detected in two cases and BoNT/A in the third case, confirming the diagnosis of infantile botulism. Despite constant nursing and monitoring, the recovery of motility was progressive, but finally complete. Dysautonomia, measured by recording heart rate variability (HRV), persisted beyond observable physical recovery. Dysautonomia was assessed using a time-domain analysis of the continuous electrocardiogram response (via non-invasive weekly 24 h Holters), which included sympathetic (SDNN) and parasympathetic indices (RMS-SD, pNN50). In all three of our patients, we observed an initial hypotonic period and a major decrease in all HRV indices. Despite observable recovery shortly after extubation, HRV time domain indices remained altered for many weeks. Because of the close monitoring afforded by hospitalization, this change in autonomic function was not accompanied by syncope, complications arising from ventricular arrhythmia, or sudden death. Our observations have important clinical implications since they emphasize the importance of pursuing cardiopulmonary monitoring following apparent functional recovery from the BoNTs.     

Effects of betel chewing on the central and autonomic nervous systems

Betel chewing has been claimed to produce a sense of well-being, euphoria, heightened alertness, sweating, salivation, a hot sensation in the body and increased capacity to work. Betel chewing also leads to habituation, addiction and withdrawal. However, the mechanisms underlying these effects remain poorly understood. Arecoline, the major alkaloid of Areca nut, has been extensively studied, and several effects of betel chewing are thought to be related to the actions of this parasympathomimetic constituent. However, betel chewing may produce complex reactions and interactions. In the presence of lime, arecoline and guvacoline in Areca nut are hydrolyzed into arecaidine and guvacine, respectively, which are strong inhibitors of GABA uptake. Piper betle flower or leaf contains aromatic phenolic compounds which have been found to stimulate the release of catecholamines in vitro. Thus, betel chewing may affect parasympathetic, GABAnergic and sympathetic functions. Betel chewing produces an increase in heart rate, blood pressure, sweating and body temperature. In addition, EEG shows widespread cortical desynchronization indicating a state of arousal. In autonomic function tests, both the sympathetic skin response and RR interval variation are affected. Betel chewing also increases plasma concentrations of norepinephrine and epinephrine. These results suggest that betel chewing mainly affects the central and autonomic nervous systems. Future studies should investigate both the acute and chronic effects of betel chewing. Such studies may further elucidate the psychoactive mechanisms responsible for the undiminished popularity of betel chewing since antiquity.     

Immunohistochemical mapping of galanin-like neurons in the rat central nervous system

Using an antiserum generated in rabbits against synthetic galanin (GA) and the indirect immunofluorescence method, the distribution of GA-like immunoreactive cell bodies and nerve fibers was studied in the rat central nervous system (CNS) and a detailed stereotaxic atlas of GA-like neurons was prepared. GA-like immunoreactivity was widely distributed in the rat CNS. Appreciable numbers of GA-positive cell bodies were observed in the rostral cingulate and medial prefrontal cortex, the nucleus interstitialis striae terminalis, the caudate, medial preoptic, preoptic periventricular, and preoptic suprachiasmatic nuclei, the medial forebrain bundle, the supraoptic, the hypothalamic periventricular, the paraventricular, the arcuate, dorsomedial, perifornical, thalamic periventricular, anterior dorsal and lateral thalamic nuclei, medial and central amygdaloid nuclei, dorsal and ventral premamillary nuclei, at the base of the hypothalamus, in the central gray matter, the hippocampus, the dorsal and caudoventral raphe nuclei, the interpeduncular nucleus, the locus coeruleus, ventral parabrachial, solitarii and commissuralis nuclei, in the A1, C1 and A4 catechaolamine areas, the posterior area postrema and the trigeminal and dorsal root ganglia. Fibers were generally seen where cell bodies were observed. Very dense fiber bundles were noted in the septohypothalamic tract, the preoptic area, in the hypothalamus, the habenula and the thalamic periventricular nucleus, in the ventral hippocampus, parts of the reticular formation, in the locus coeruleus, the dorsal parabrachial area, the nucleus and tract of the spinal trigeminal area and the substantia gelatinosa, the superficial layers of the spinal cord and the posterior lobe of the pituitary. The localization of the GA-like immunoreactivity in the locus coeruleus suggests a partial coexistence with catecholaminergic neurons as well as a possible involvement of the GA-like peptide in a neuroregulatory role.     

Comparison of transduction efficiency of recombinant AAV serotypes 1, 2, 5, and 8 in the rat nigrostriatal system

Enhanced delivery and expression of genes in specific neuronal systems is critical for the development of genetic models of neurodegenerative disease and potential gene therapy. Recent discovery of new recombinant adeno-associated viral (rAAV) capsid serotypes has resulted in improved transduction efficiency, but expression levels, spread of transgene, and potential toxicity can differ depending on brain region and among species. We compared the transduction efficiency of titer-matched rAAV 2/1, 2/5, and 2/8 to the commonly used rAAV2/2 in the rat nigrostriatal system via expression of the reporter transgene, enhanced green fluorescent protein. Newer rAAV serotypes 2/1, 2/5, and 2/8 demonstrated marked increase in transduction and spread of enhanced green fluorescent protein expression in dopaminergic nigrostriatal neurons and projections to the striatum and globus pallidus compared to rAAV2/2 at 2 weeks post-injection. The number of nigral cells transduced was greatest for rAAV2/1, but for serotypes 2/5 and 2/8 was still two- to threefold higher than that for 2/2. Enhanced transduction did not cause an increase in glial cell response or toxicity. New rAAV serotypes thus promise improved gene delivery to nigrostriatal system with the potential for better models and therapeutics for Parkinson disease and other neurodegenerative disorders.     

Calcitonin gene-related peptide: detailed immunohistochemical distribution in the central nervous system

With the use of an antiserum generated in rabbits against synthetic human calcitonin gene-related peptide (CGRP) the distribution of CGRP-like immunoreactive cell bodies and nerve fibers was studied in the rat central nervous system. A detailed stereotaxic atlas of CGRP-like neurons was prepared. CGRP-like immunoreactivity was widely distributed in the rat central nervous system. CGRP positive cell bodies were observed in the preoptic area and hypothalamus (medial preoptic, periventricular, anterior hypothalamic nuclei, perifornical area, medial forebrain bundle), premamillary nucleus, amygdala medialis, hippocampus and dentate gyrus, central gray and the ventromedial nucleus of the thalamus. In the midbrain a large cluster of cells was contained in the peripeduncular area ventral to the medial geniculate body. In the hindbrain cholinergic motor nuclei (III, IV, V, VI, VII XII) contained CGRP-immunoreactivity. Cell bodies were also observed in the ventral tegmental nucleus, the parabrachial nuclei, superior olive and nucleus ambiguus. The ventral horn cells of the spinal cord, the trigeminal and dorsal root ganglia also contained CGRP-immunoreactivity. Dense accumulations of fibers were observed in the amydala centralis, caudal portion of the caudate putamen, sensory trigeminal area, substantia gelatinosa, dorsal horn of the spinal cord (laminae I and II). Other areas containing CGRP-immunoreactive fibers are the septal area, nucleus of the stria terminalis, preoptic and hypothalamic nuclei (e.g., medial preoptic, periventricular, dorsomedial, median eminence), medial forebrain bundle, central gray, medial geniculate body, peripeduncular area, interpeduncular nucleus, cochlear nucleus, parabrachial nuclei, superior olive, nucleus tractus solitarii, and in the confines of clusters of cell bodies. Some fibers were also noted in the anterior and posterior pituitary and the sensory ganglia. As with other newly described brain neuropeptides it can only be conjectured that CGRP has a neuroregulatory action on a variety of functions throughout the brain and spinal cord.     

A description of the upper thoracic autonomic nervous system in the rhesus monkey (Macaca mulatta)

The purpose of this study was to describe the autonomic innervation of the carotid sinus and heart in the rhesus monkey. Nine male rhesus monkeys (Macaca mulatta) and one male crab-eating macaque (M. fascicularis) were carefully dissected from the origin of the vagus nerves and superior cervical ganglia to the level of the fourth thoracic ganglion. The specimens were either freshly killed or obtained no later than 24 hours post mortem. The macaque monkeys were found to possess an innervation pattern that displayed features common to dog (connections between the vagus nerves and middle cervical ganglia), baboon (distinct cervical sympathetic and cervical vagal nerve trunks), and man (nerves projecting from the middle cervical and stellate ganglia to the heart). Distinct inferior cervical and first thoracic ganglia were never seen, but rather, large and well defined stellate ganglia were found. The macaque innervation pattern, when considered as a whole, most closely resembled the baboon.     

2,3-Dimethylpyrazine (3DP) and 2,5-dimethyl-4-hydroxy-3(2H)-furanone (DMHF) generated by the Maillard reaction in foods affect autonomic nervous activity and central nervous activity in human

ABSTRACT

This study investigated the effect of the odors generated by the glycine/glucose Maillard reaction and the potent odorants 2,3-dimethylpyrazine (3DP) and 2,5-dimethyl-4-hydroxy-3(2H)-furanone (DMHF) on the human mood and integrative physiological activity. The score of certain subjective moods, especially anger-hostility, and tension-anxiety were decreased significantly after inhalation of the Maillard reaction sample and DMHF, and fatigue-inertia mood was also significantly decreased by DMHF, suggesting a sedative effect of these odors on mood, while 3DP had no effect. Miosis rate and fingertip temperature increased significantly following inhalation of the odor from the Maillard reaction sample and both potent odorants, suggesting that the parasympathetic nervous system dominates through suppression of the sympathetic activity. The physiological relaxing effect of these odors was also confirmed by decreased flicker frequency value and decreased oxyhemoglobin in the prefrontal cortex.     

Specific populations of basal ganglia output neurons target distinct brain stem areas while collateralizing throughout the diencephalon

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Modulation by GABA of neuroplasticity in the central and peripheral nervous system

Apart from being a prominent (inhibitory) neurotransmitter that is widely distributed in the central and peripheral nervous system, -aminobutyric acid (GABA) has turned out to exert trophic actions. In this manner GABA may modulate the neuroplastic capacity of neurons and neuron-like cells under various conditions in situ and in vitro. In the superior cervical ganglion (SCG) of adult rat, GABA induces the formation of free postsynaptic-like densities on the dendrites of principal neurons and enables implanted foreign (cholinergic) nerves to establish functional synaptic contacts, even while preexisting connections of the preganglionic axons persist. Apart from postsynaptic effects, GABA inhibits acetylcholine release from preganglionic nerve terminals and changes, at least transiently, the neurochemical markers of cholinergic innervation (acetylcholinesterase and nicotinic receptors). In murine neuroblastoma cells in vitro, GABA induces electron microscopic changes, which are similar in principle to those seen in the SCG. Both neuroplastic effects of GABA, in situ and in vitro, could be mimicked by sodium bromide, a hyperpolarizing agent. In addition, evidence is available that GABA via A- and/or B-receptors may exert direct trophic actions. The regulation of both types of trophic actions (direct, receptor-mediated vs. indirect, bioelectric activity dependent) is discussed.Special issue dedicated to Dr. Claude Baxter.     

Comparative characterization of the nervous system of the Turbellaria

Initial stages of the centralization of the nervous apparatus in the Turbellaria can be traced through a comparison of the structure of the nervous system in various representatives of the class. The most primitive state, found in the Acoela, is predominantly plexiform with a varying number of longitudinal trunks. Three, and in some cases four, longitudinal trunks are found in the Proseriata and Temnocephalida. Commissures appear in the Macrostomida and all higher orders and form an orthogon. Brain shape varies from ring-shaped in the Acoela to bilobed in the Neorhabdocoela. While the nervous system of the Polycladida is peculiar, having numerous lateral trunks and separation of dorsal and ventral parts of the nervous system, the development of the nervous system in Müller's larvae of polyclads shows it is of an orthogonal type comparable to other platyhelminths. Transition to parasitism is accompanied by some progressive transformations in the structure of the nervous system.