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Preoptic neuronal circuit: atrial natriuretic peptide-containing neurons are sensitive to acute and chronic alterations in body fluid volume.

Atrial antriuretic peptide (ANP) concentrations were determined in rostral preoptic midline structures (organum vasculosum laminae terminalis, periventricular and medial preoptic nuclei) and in the subfornical organ by radioimmunoassay in rats with acute volume load and volume depletion, as well as during water deprivation. ANP-containing neuronal elements in all four areas (to a lesser extent in the medial preoptic nucleus) reacted very sensitively to acute and chronic changes in body fluid volume: volume load resulted in an elevation, volume depletion in a depletion in ANP concentrations. These alterations were significant and completely matched changes in plasma ANP concentrations. Water deprivation increased ANP levels on the first experimental day, followed by a marked depletion in the organum vasculosum laminae terminalis, subfornical organ and the periventricular preoptic nucleus. It is hypothesized that three major neuropeptides (angiotensin II, vasopressin, ANP) regulate body fluid volume through a close neuronal network along a subfornical organ-preoptic-hypothalamic axis. The subfornical organ, which is very rich in angiotensin II and ANP receptors, serves as an open gate for circulating hormones and is neuronally interconnected with volume-sensitive ANP neurons in the preoptic area (organum vasculosum laminae terminalis and preoptic periventricular nucleus). Neurons in the subfornical organ and the preoptic area project to the supraoptic and paraventricular nuclei and control the activity of vasopressin-synthesizing neurosecretory cells.

Animals↗

Learning-dependent dendritic hypertrophy of cerebellar stellate cells: plasticity of local circuit neurons.

Recent work has shown that motor learning, but not mere motor activity, changes the morphology of Purkinje cells, the major projection neurons of the cerebellar cortex. In the present study we examined how motor skill learning affects the dendritic morphology of the stellate local circuit neurons. Adult female rats were either trained to complete a complex motor learning task or forced to traverse a flat, obstacle-free runway. Golgi impregnated stellate cells were then traced via camera lucida and their dendritic arborizations examined with a concentric ring analysis. Results showed the motor learning animals to have significantly greater stellate cell dendritic arborizations than the activity controls. Thus these local circuit neurons exhibit morphological plasticity.

Animals↗

A prosencephalic neuronal circuit possibly involved in modulation of pain.

Both anatomical and physiological studies in cats substantiated the existence of a thalamus-cortex-thalamus neuronal circuit in which neurons in the centre median send fibers to wide areas of the cerebral cortex and the cerebral cortex, the motor cortex in particular, may send the fibers back to the parafascicular nucleus. The cortical neurons concerned tend to discharge spontaneously and constantly. These spontaneous discharges can be readily inhibited by the corticopetal impulses from the centre median, which itself can be activated by general afferent impulses. On the basis of this observation it is assumed that constantly discharging corticothalamic neurons may exert a tonic excitatory influence on the pain-receiving center, parafascicular nucleus, so as to keep it in a state of constant alertness to the tissue-damaging danger signals and that the inhibitory action of the ascending fibers from centre median would serve to suspend the excitatory action of the cortex on the parafascicular nucleus, resulting in relief of pain. The corticofugal fibers in this forebrain circuit terminating in the centromedian nucleus may reinforce the inhibitory action of the centromedian neurons so as to inhibit the spontaneous discharges of the cortical neurons . A self-regulating mechanism is thus formed by which a stabilized state of brain excitability can be maintained.

Animals↗

Short latency activation of local circuit neurons in the cat somatosensory cortex.

Intracellular horseradish peroxidase (HRP) study was performed in the cat primary somatosensory cortex (SI) under Nembutal anesthesia. Response properties of neurons were analysed with stimulation of the peripheral nerve (superficial radial nerve; SR) and thalamic ventrobasal nucleus (VB). A total number of 23 cells (15 in layers III and IV, 6 in layer V and 2 in layer VI) were identified morphologically as local circuit neurons with intracellular HRP staining. The latencies of SR-induced (7.7-8.5 ms) as well as VB-induced excitatory postsynaptic potentials (EPSPs) (1.3-1.5 ms) were significantly shorter than those of pyramidal neurons (9.1-10.6 ms for SR and 1.6-2.8 ms VB EPSPs). Morphological features of identified local circuit neurons are all, except one in layer VI, aspiny and presumed to be inhibitory in nature. The present study indicates that presumed inhibitory interneurons in the cat SI could be activated first by thalamic inputs among cortical neurons and set to inhibit the output cells for the sharp contrast in the sensory processing.

Animals↗

Organization of the neuronal circuits in the central nervous system during development.

UNLABELLED: The human brain is a product of genetic instructions, cellular interactions and influences of innate activity and external stimulation. The formation of the neural tube and the patterning of the brain are determined by homeotic genes. After a prosencephalic phase with the formation of the hemispheres, the neurons prolipherate to number about 100 billion halfway through gestation. They also migrate to their final positions in an inside-outside fashion with the newly formed neurons at the outer layer of the cortex, followed by synaptogenesis, programmed cell death and organization of the neuronal circuits. This phase is probably determined not only by genes but also by innate activity, which for example has been detected in the foetal retina: "Cells that fire together wire together while those which don't won't". CONCLUSION: Development of the neuronal circuits in the CNS can be viewed as epigenetic. i.e. many different components must come together at the right time and place.

Cell Movement↗

Altered distribution of parvalbumin-immunoreactive local circuit neurons in the anterior cingulate cortex of schizophrenic patients.

Several lines of evidence support an involvement of the anterior cingulate cortex in the pathophysiology of schizophrenia. Immunocytochemical techniques using antibodies against calcium-binding proteins permit a selective demonstration of certain subgroups of cortical GABAergic interneurons. The anterior cingulate cortex from the brains of schizophrenic patients and control subjects was studied with an antibody against parvalbumin. The immunoreactive structures were assessed qualitatively and quantitatively. Parvalbumin immunoreactivity was detected in a subpopulation of GABAergic local circuit neurons, in axonal structures (including axon cartridges) and in diffuse, band-like neuropil material. Schizophrenic anterior cingulate cortex was found to contain the same interneuron types as controls, but displayed a significant increase of parvalbumin-immunoreactive neuronal soma profiles in layers Va and Vb, whereas the total neuronal density determined in Nissl preparations showed no difference in the two groups. A higher density of parvalbumin-positive local circuit neurons may indicate an increased inhibition of projection neurons, thus altering the neuronal output pattern of the anterior cingulate cortex in schizophrenia.

Adult↗

Development of neuronal circuits and behaviors in the medicinal leech.

We are studying the neuronal mechanisms responsible for establishing circuitry underlying the local bending response in the medicinal leech. Local bending replaces an embryonic behavior, circumferential indentation, during the time of initial chemical synaptogenesis in leech embryos. We found that the electrical connections among the motor neurons are established first, about 5% of embryonic time (almost 2 full days) before chemical connections form. The inhibitory connections from muscle inhibitors to muscle excitors are, we hypothesize, responsible for the emergence of local bending. We have also found that the central processes of the excitors--but not the inhibitors--have much longer central processes when their peripheral processes are kept from contacting their target muscles. This system should allow us to test ideas about how individual neurons find their appropriate targets to form functional neuronal circuits.

Animals↗

Abnormal local-circuit neurons in epilepsia partialis continua associated with focal cortical dysplasia.

A limited cortical resection including the rolandic fissure and the pre- and postcentral cortical regions was carried out in a patient suffering from epilepsia partialis continua resistant to antiepileptic drugs. The histological examination revealed several foci of very large neurons distributed with no laminar organization in the depth of the rolandic fissure and in the crown of the primary motor and primary somatosensory areas; these lesions were consistent with focal cortical dysplasia. In addition, decreased numbers of neurons, astrocytosis and proliferation of capillaries, compatible with chronic tissue necrosis, were found in the inferior regions of the banks of the rolandic fissure. Subpopulations of local-circuit neurons were examined with parvalbumin, calbindin D-28k and somatostatin immunocytochemistry. Focal areas of cortical dysplasia contained abnormal immunoreactive neurons. Huge parvalbumin-immunoreactive cells were distributed at random and resembled axo-axonic (chandelier) and basket neurons. Abnormal calbindin D-28k-immunoreactive cells were reminiscent of double-bouquet neurons and multipolar cells. Very large somatostatin-immunoreactive cells were seldom observed in the dysplastic foci. On the other hand, areas of tissue necrosis displayed massive reduction of immunoreactive cells and fibers. Abnormalities in the morphology and distribution of local-circuit (inhibitory) neurons observed here for the first time in focal cortical dysplasia may have a pivotal role in the appearance and prolongation of electrical discharges and continuous motor signs in human focal epilepsy.

Adolescent↗

Modulation of intracortical neuronal circuits in human hand motor area by digit stimulation.

We investigated the changes in intracortical neuronal circuits of the hand motor cortex following sensory stimulation of the fingers in 11 healthy subjects. Motor evoked potentials (MEPs) were recorded from intrinsic hand muscles (right first dorsal interosseous and abductor digiti minimi muscles). Electrical stimulation was applied to a digit near (homotopic) or distant (heterotopic stimulation) from each muscle. The right index or little finger was stimulated electrically, followed by single- or paired-pulse transcranial magnetic stimulation (TMS) at an interval of 25, 200, 600, 1,000 or 1,400 ms. Paired-pulse TMS was applied with interstimuli intervals of 2 ms or 12 ms and was expected to stimulate inhibitory or facilitatory intracortical circuits, respectively. MEPs induced by single-pulse TMS were significantly suppressed 200, 600, and 1,000 ms after heterotopic and homotopic stimuli. Intracortical facilitation was significantly enhanced only after homotopic stimuli and such enhancement was maximal 200 ms after digit stimulation. Intracortical inhibition was slightly weakened after homotopic stimulation but this effect did not reach statistical significance ( P=0.25). Our results show that sensory feedback can modify intracortical and corticospinal motor excitability and that intracortical facilitation can be enhanced in a topographic-specific way especially at long latencies. These findings suggest that indirect pathways, probably through somatosensory cortex and other areas, enhance intracortical motor excitability in a somatotopically organized manner.

Adult↗

Chronic lead exposure induces alterations on local circuit neurons.

The effect of chronic lead exposure in neonatal rats was examined, particularly on hippocampal local circuit neurons (LCN). Chronic lead was administered to rat pups in the first week of life through the mother milk. During the lactation period the mother only drank water containing 1 g% lead acetate (w/v) -subclinical dose. Following weaning, the young rats were treated for 3 months with the same concentration of lead-adulterated water. Electron microscopy studies were made at 30, 45, 60, 75 and 90 days of age. After 2 months of lead exposure, irregular outline and dark-condensed cytoplasm in non-pyramidal neurons, in basket and in granule cells were found. Within the neuropil, some beaded and smooth dendrites, as well as some axons and synaptic terminals, appeared condensed and darker than the surrounding elements. Coincident with the LCN alterations, astrocytes showed an increment of glial filaments. These results suggested that the functional activity of LCN could be modified by the observed changes. Such ultrastructural modifications could be a morphological substrate for the subtle neuropsychological deficits of rats chronically exposed to relatively low concentration of lead.

Animals↗

The influences of somatic and dendritic inhibition on bursting patterns in a neuronal circuit model.

The balance between inhibition and excitation plays a crucial role in the generation of synchronous bursting activity in neuronal circuits. In human and animal models of epilepsy, changes in both excitatory and inhibitory synaptic inputs are known to occur. Locations and distribution of these excitatory and inhibitory synaptic inputs on pyramidal cells play a role in the integrative properties of neuronal activity, e.g., epileptiform activity. Thus the location and distribution of the inputs onto pyramidal cells are important parameters that influence neuronal activity in epilepsy. However, the location and distribution of inhibitory synapses converging onto pyramidal cells have not been fully studied. The objectives of this study are to investigate the roles of the relative location of inhibitory synapses on the dendritic tree and soma in the generation of bursting activity. We investigate influences of somatic and dendritic inhibition on bursting activity patterns in several paradigms of potential connections using a simplified multicompartmental model. We also investigate the effects of distribution of fast and slow components of GABAergic inhibition in pyramidal cells. Interspike interval (ISI) analysis is used for examination of bursting patterns. Simulations show that the inhibitory interneuron regulates neuronal bursting activity. Bursting behavior patterns depend on the synaptic weight and delay of the inhibitory connection as well as the location of the synapse. When the inhibitory interneuron synapses on the pyramidal neuron, inhibitory action is stronger if the inhibitory synapse is close to the soma. Alterations of synaptic weight of the interneuron can be compensatory for changes in the location of synaptic input. The relative changes in these parameters exert a considerable influence on whether synchronous bursting activity is facilitated or reduced. Additional simulations show that the slow GABAergic inhibitory component is more effective than the fast component in distal dendrites. Taken together, these findings illustrate the potential for GABAergic inhibition in the soma and dendritic tree to play an important modulatory role in bursting activity patterns.

Action Potentials↗

Geometry of rubrospinal, rubroolivary, and local circuit neurons in the macaque red nucleus.

The primate red nucleus consists of three main neuron subpopulations, namely, rubrospinal neurons in the magnocellular nucleus, rubroolivary cells in the parvocellular nucleus, and local circuit neurons in both subnuclei: Each subpopulation has unique cerebellar and neocortical inputs. The structural framework for the interactions of these rubral subpopulations remains poorly defined and was the focus of this study in six macaques. Somata of rubrospinal neurons, dorsolateral-spinal (DL-spinal) neurons, as defined in the accompanying paper (Burman et al. [2000] J. Comp. Neurol., this issue), and rubroolivary neurons were labeled retrogradely first with Fast Blue injected either into the cervical spinal cord or the inferior olive. The soma/dendrite profiles of selected cells (53 rubrospinal, 19 DL-spinal, and 17 rubroolivary cells) were visualized by the intracellular injection of Lucifer Yellow/biocytin in fixed slices (400 microm thick) of midbrain. The descriptive statistics of the somata and the dendritic arborization of each rubral neuron type were established. Projection neuron subpopulations had similar but differentiable soma/dendrite profiles, with four to six slender, spine-bearing dendritic trees radiating out approximately 400 microm from the soma. Twelve presumed interneurons, all in the parvocellular nucleus, differed from projection neurons in that they had smaller somata and many slender, spine-bearing segments that constituted the multibranching dendrite profile that radiated out approximately 250 microm from the soma. A tentative model of the macaque rubral microcircuitry was developed, and its functional implications were explored. It incorporated 1) the known topography of the nucleus and its connections, 2) our data specifying the soma/dendrite morphology of the three main rubral neuron types, and 3) the ultrastructure reported by other laboratories of intrarubral synaptic connections.

Animals↗

Functional and morphological changes in the hippocampal neuronal circuits associated with epileptic seizures.

PURPOSE: We review what is currently known about functional and morphologic plasticity of hippocampal neuronal circuits in animal epilepsy models. RESULTS: Perforant-path kindling has been shown to enhance excitatory synaptic transmission in the dentate gyrus significantly, and this enhancement has lasted for > or =1 month after kindling. However, in our rapid kindling experiment with an interstimulus interval of 5 min, perforant-path kindling resulted in behavioral convulsions and prolonged the afterdischarge duration, but dentate synaptic transmission remained depressed during kindling. CONCLUSIONS: These results indicate that kindling-induced synaptic potentiation is not necessary for kindling development. Conversely, epileptic seizures have led to the anomalous sprouting of mossy fibers, a process thought to induce hyperexcitation of granule cells. We conclude that the sprouting of mossy fibers did not play a critical role in kindling, because we observed no significant correlation between the mossy fiber sprouting and kindling development. Epileptic seizures also have been shown to increase gamma-aminobutyric acid (GABA)A receptor-mediated inhibition during interictal periods. Although this strengthening of GABAergic inhibition is likely to be a defensive measure against seizure initiation, some studies have suggested that another type of GABAergic response facilitates seizure activity. The possibility of GABAA receptor-mediated excitation during ictal periods is theoretically examined.

Animals↗

[From neuronal recovery to the reorganisation of neuronal circuits: a review of the functions of sleep].

AIM: To analyse the data and concepts that have been produced in relation to one of the functions that have been suggested for sleep, namely, neuronal recovery. DEVELOPMENT: Sleep is a state of consciousness that is different to that of arousal. Mammals devote an important part of their lives to sleeping; for example, as humans, we sleep for a third of our lives, but why do we spend so much time in a state where we lose contact with our surroundings? What would happen if we didn't sleep? Total sleep deprivation alters cognitive processes such as memory or attention, and if this deprivation is prolonged, the individual deteriorates and dies. It has been suggested that sleep provides the organism with time to recover from the wear and tear that occurs during the waking state and, given that the first effects of the absence of sleep are seen to affect processes that are directly dependent on the brain, it has been claimed that its main purpose is to allow neuronal recovery. In this work we analyse some of the studies on the effects of total sleep deprivation in humans and rats, as well as the relationship between sleep and the neurotrophin system, which promotes neuronal survival and recovery. Finally, the latest theories about the function of sleep are discussed. CONCLUSIONS: Neuron recovery is not the ultimate purpose of sleep; rather it is to allow for maintenance and reorganisation of neuronal circuits, including new synapse formation, which enables existing neuronal networks to be modified by the effect of experience, and all this makes it possible for the brain to work properly and to adapt itself to the environment.

Animals↗

Postnatal changes of local neuronal circuits involved in activation of jaw-closing muscles.

Feeding behaviour in mammals changes from suckling to mastication during postnatal development and the neuronal circuits controlling feeding behaviour should change in parallel to the development of orofacial structures. In this review we discuss the location of excitatory premotor neurons for jaw-closing motoneurons (JCMNs) and postnatal changes of excitatory synaptic transmission from the supratrigeminal region (SupV) to JCMNs. We show that neurons located in SupV and the reticular formation dorsal to the facial nucleus most likely excite JCMNs. Excitatory inputs from SupV to JCMNs are mediated by activation of glutamate and glycine receptors in neonatal rats, whereas glycinergic inputs from SupV to JCMNs become inhibitory with age. We also show that the incidence of post-spike afterdepolarization increases during postnatal development, whereas the amplitude and half-duration of the medium-duration afterhyperpolarization decrease with age. Such postnatal changes in synaptic transmission from SupV to JCMNs and membrane properties of JCMNs might be involved in the transition from suckling to mastication.

Animals↗

Differential expression of connexins during neocortical development and neuronal circuit formation.

Gap junctions are membrane channels that mediate the direct passage of ions and molecules between adjacent cells. Recent tracer coupling and optical recording studies have revealed the presence of gap junction-mediated communication between neurons during neocortical development. We have visualized gap junctions in the developing rat cerebral cortex with electron microscopy and studied the pattern of expression and cellular localization of connexins 26, 32, and 43 that take part in their formation. We found that these connexins (Cxs) are expressed differentially during development, and their patterns of expression are correlated with important developmental events such as cell proliferation, migration, and formation of cortical neuronal circuits. Specifically, we observed that the developmental profile of Cx 26 during the first 3 weeks of postnatal life matched closely the development of neuronal coupling, suggesting that coupled neurons use this gap junction protein during circuit formation in the cortex. The subsequent diminution of Cx 26 was mirrored by an increase in Cx 32 immunoreactivity, which became pronounced at the late stages of cortical maturation. In contrast, Cx 43 was localized in the cortex throughout the period of development. Its localization in radial glial fibers closely associated with migrating neurons suggests that this Cx may be involved in neuronal migration.

Animals↗

Schizophrenia and the parvalbumin-containing class of cortical local circuit neurons.

OBJECTIVE: The purpose of this study was to test the hypothesis that abnormalities in the parvalbumin-containing subclass of local circuit neurons contribute to altered gamma-aminobutyric acid (GABA) neurotransmission in the prefrontal cortex of schizophrenic subjects. METHOD: Profile counts and somal size measures were made of parvalbumin-immunoreactive neurons in areas 9, 46, and 17 from 15 matched pairs of schizophrenic and normal comparison subjects. RESULTS: No differences in relative density, laminar distribution, or somal size of labeled neurons were found in any region. CONCLUSIONS: These findings suggest that altered GABA neurotransmission in schizophrenia is due to either abnormalities in other sub-populations of prefrontal cortical GABA neurons or abnormalities in the parvalbumin-containing subclass that could not be detected in the present study.

Cell Count↗

Optical probing of neuronal circuit dynamics: genetically encoded versus classical fluorescent sensors.

During the past few decades, optical methods for imaging activity in networks composed of thousands of neurons have been developed. These techniques rely mainly on organic-chemistry-based dyes as indicators of Ca(2+) and membrane potential. However, recently a new generation of probes, genetically encoded fluorescent protein sensors, has emerged for use by physiologists studying the operation of neuronal circuits. We critically review the development of these new probes, and analyze objectives and experimental conditions in which classical probes are likely to prevail and where the fluorescent protein sensors will open paths to previously unexplored territories of functional neuroimaging.

Animals↗