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PubMed1997

Control of computational dynamics of coupled integrate-and-fire neurons.

Generation and control of different dynamical modes of computational processes in a net of interconnected integrate-and-fire neurons are demonstrated. A net architecture resembling a generic cortical structure is formed from pairs of excitatory and inhibitory units with excitatory connections between and inhibitory connections within pairs. Integrate-and-fire model neurons derived from detailed conductance-based models of neocortical pyramidal cells and fast-spiking interneurons are employed for the excitatory and inhibitory units, respectively. Firing-rate adaptation is incorporated into the excitatory units based on the regulation of the slow afterhyperpolarization phase of action potentials by intracellular calcium ions. Saturation of synaptic conductances is implemented for the interconnections between units. It is shown that neuronal adaptation of the excitatory units can generate richer net dynamics than relaxation to fixed-point attractors-in a pattern space. At strong adaptivity, i.e. when the neuronal excitability is strongly influenced by the preceding activity, complex dynamics of either aperiodic or limit-cycle character are generated in both the pattern space and the phase space of all dynamical variables. This regime corresponds to an exploratory mode of the system, in which the pattern space can be searched. At weak adaptivity, the dynamics are governed by fixed-point attractors in the pattern space, and this corresponds to a mode for retrieval of a particular pattern. In the brain, neuronal adaptivity can be regulated by various neuromodulators. The results are in accordance with those recently obtained by means of more abstract models formulated in terms of mean firing rates. The increased realism makes the present model reveal more detailed mechanisms and strengthens the relevance of the conclusions to biological systems. The simplicity and realism of the coupled integrate-and-fire neurons make the present model useful for studies of systems in which the temporal aspects of neural coding are important.

Animals↗

PubMed2005

Delayed postnatal settlement of cerebellar Purkinje cells in vermal lobules VI and VII of the mouse.

The postnatal development of the ganglionic (Purkinje) layer was studied in the mouse cerebellum from P0 to young adulthood with special emphasis to vermal lobules VI-VII (oculomotor vermis) in the mouse. In order to visualize Purkinje cells (PCs), toluidine blue staining of resin-embedded semithin sections and calbindin immunohistochemistry were utilized. The number of PCs in the whole cerebellum was 199,080+/-2966 at postnatal day eight (P8), 222,000+/-2979 at P20 and nearly the same, 225,800+/-7549 in young adults; i.e., there was an approximately 13.4% increase of PCs between P8 and adults. The number of PC somata aligned into a rostrocaudal stripe along the developing ganglionic layer increased by about 24% in vermal cerebellar lobule III but much more markedly (i.e., by 49%) in VI+VII between P6 and young adulthood. Between P6 and P16, the increase of the number of PCs in the ganglionic layer of lobules VI and VII resulted in the (delayed) completion of PC layer, caused by the (late) alignment of rostrocaudally dispersed PCs, although late postnatal migration of a smaller population of these cells cannot be excluded either. It is concluded that the oculomotor vermis belongs to the latest developing cerebellar cortical structures, which could be the reason for its frequent involvement in developmentally related disturbances and disorders.

Animals↗

PubMed1996

The dorsomedial and dorsolateral forebrain of the zebra finch, Taeniopygia guttata: a Golgi study.

Neurones in the zebra finch dorsal forebrain (hippocampal and lateral corticoid complexes) were described and located using Golgi methods. We distinguish two main classes of neurones, spinous with distant projecting axons, and aspinous with local axons. Spinous neurones are subclassified into bitufted pyramids, localised in the medial hippocampus, modified bitufted pyramids in the intermediate corticoid area, multipolar neurones in the parahippocampal area, lateral hippocampus and corticoid complex, and stellate neurones in the corticoid complex. Among the aspinous neurones, we distinguish neurones with basket axons, dense pericellular axons, radial axons, and net-like axons, and horizontal cells seen in the dorsolateral corticoid area. This group includes sparsely spinous neurones found in the intermediate corticoid area. On the basis of the neuronal characteristics, we divide the hippocampal complex into 5 fields: medial and lateral hippocampus, parahippocampal area, central field of the parahippocampal area, and crescent field. The lateral corticoid complex is subdivided into an intermediate corticoid area and a dorsolateral corticoid area. We conclude that the avian dorsal forebrain is an assembly of fields interconnected by axonal collaterals. The medial hippocampus and possibly the intermediate corticoid area display a primitive cortex-like organisation, whereas the other fields lack any sign of cortical structure.

Animals↗

PubMed1996

Immunohistochemical mapping of perineuronal nets containing chondroitin unsulfated proteoglycan in the rat central nervous system.

Subsets of neurons ensheathed by perineuronal nets containing chondroitin unsulfated proteoglycan have been immunohistochemically mapped throughout the rat central nervous system from the olfactory bulb to the spinal cord. A variable proportion of neurons were outlined by immunoreactivity for the monoclonal antibody (Mab 1B5), but only after chondroitinase ABC digestion. In forebrain cortical structures the only immunoreactive nets were around interneurons; in contrast, throughout the brainstem and spinal cord a large proportion of projection neurons were surrounded by intense immunoreactivity. Immunoreactivity was ordinarily found in the neuropil between neurons surrounded by an immunopositive net. By contrast, within the pyriform cortex the neuropil of the plexiform layer was intensely immunoreactive even though no perineuronal net could be found. The presence of perineuronal nets could not be correlated with any single class of neurons; however a few functionally related groups (e.g., motor and motor-related structures: motor neurons both in the spinal cord and in the efferent somatic nuclei of the brainstem, deep cerebellar nuclei, vestibular nuclei; red nucleus, reticular formation; central auditory pathway: ventral cochlear nucleus, trapezoid body, superior olive, nucleus of the lateral lemniscus, inferior colliculus, medial geniculate body) were the main components of the neuronal subpopulation displaying chondroitin unsulfated proteoglycans in the surrounding extracellular matrix. The immunodecorated neurons found in the present study and those shown by different monoclonal antibodies or by lectin cytochemistry, revealed consistent overlapping of their distribution patterns.

Animals↗

PubMed2003

Activation of cerebellum and basal ganglia on volitional swallowing detected by functional magnetic resonance imaging.

Although regions of the sensorimotor cortex, insula, and anterior cingulate gyrus are reported to be activated during swallowing, findings concerning contributions of the cerebellum and basal ganglia have been contradictory. We investigated cerebellar and basal ganglionic activation using functional magnetic resonance imaging (fMRI). In 11 subjects, single-shot gradient-echo echoplanar image volumes sensitive to BOLD contrast were acquired in block design fashion using an oblique orientation covering both cerebrum and cerebellum. Using statistical parametric mapping, regional activation upon swallowing was observed in the sensorimotor cortex, insula, cerebellum, putamen, globus pallidus, thalamus, anterior cingulate gyrus, supplementary motor area, superior temporal gyrus, and substancia nigra. The cerebellum was activated bilaterally, especially on the left; activation of the putamen and globus pallidus was also found bilaterally. Thus, volitional swallowing involves the cerebellum and basal ganglia as well as cortical structures. The method used was well tolerated by normal subjects and should also be applicable to patients with dysphagia.

Adult↗

PubMed2005

Oculomotor inhibition in children with and without attention-deficit hyperactivity disorder (ADHD).

The aim of the present study was to distinguish between a general deficit in oculomotor control and a deficit restricted to inhibitory functions in children with attention deficit hyperactivity disorder (ADHD). In addition, we were interested in differentiating between a general inhibition deficit and deficient subfunctions of inhibition. We used a prosaccade task to measure general oculomotor abilities in 22 children with ADHD and in age- and gender-matched healthy controls. A fixation, an antisaccade and a countermanding saccade task were used to measure specific aspects of oculomotor inhibition. Two major results were obtained: First, our prosaccade task suggests similar saccadic response preparation and saccadic accuracy in the ADHD compared to the control children. Secondly, the fixation and the countermanding saccade task indicate deficits on measures of oculomotor inhibition in the ADHD group. While patients were specifically impaired in stopping an already initiated response or in suppressing exploratory saccades in a novel situation, inhibition of a prepotent response was not deficient. Our data thus indicate an underlying impairment in cognitive inhibition in ADHD that has been associated with prefrontal lobe functions. More specifically, as the anterior cingulate gyrus has been associated with the countermanding saccade task and group differences were most pronounced in this paradigm our data are in line with imaging data stressing the importance of this cortical structure in the pathophysiology of ADHD.

Adolescent↗

PubMed2006

Cerebrogenic cardiac arrhythmias: cortical lateralization and clinical significance.

That the brain may be involved in cardiovascular regulation has been acknowledged for over a century. That cardiac arrhythmias may result from cortical derangement has been less well recognized. That cortical cardiac representation may be lateralized is even more controversial. Recent evidence implicates several cortical structures, especially the insula, in cardiac rate and rhythm control. Experimental models indicate that insular lesions may be arrhythmogenic. Accumulating data show similar lesion effects in humans. In the rat, monkey and man sympathetic cardiovascular control is generally represented in the right insula, although pronounced insulo-insular connectivity has been demonstrated. Proarrhythmic shifts in cardiac sympathovagal balance occur after human stroke, including left insular lesions. This evidence implicates the cortex in the promotion and even generation of cardiovascular dysfunction under appropriate circumstances.

Animals↗

PubMed2001

Post-stroke epilepsy.

Seizures occur in about 10% of stroke patients. Hence, stroke is the most common cause of seizures and epilepsy in the elderly population. Five percent are early-onset seizures (peak onset within the first day after the stroke) and another 5% are late-onset seizures (peak onset within 6 to 12 months after the stroke). Epilepsy (i.e., recurrent seizures) develops in 3% to 4% of the stroke patients (in about one third of the patients with early-onset seizures and about one half of the patients with late-onset seizures). There is a strong positive correlation between stroke severity and the risk of post-stroke seizures; the risk is very low in mild strokes. Seizures are more common in hemorrhagic stroke and in stroke with cortical involvement. Whether this is due to the hemorrhagic component or the cortical involvement per se, or a reflection of more severe strokes among patients with hemorrhagic strokes and lesions involving cortical structures, is not clear. The influence of seizures on outcome is still a matter of controversy. Although epileptic seizures are considered easy to control, this is not supported by evidence from randomized controlled trials.

Aged↗

PubMed2004

Management of seizures in critically ill patients.

For many neurologists, seizures in critically ill patients represent a difficult problem. Etiology can be elusive because of the complexity of the environment, and treatment decisions can be compromised by the paucity of evidence-based guidelines. Emerging data support a higher than previously thought incidence of nonconvulsive epileptic activity in this patient population, which is another important consideration. Although a seizure in the intensive care unit should be treated aggressively, prophylactic antiepileptic drug administration is dependent on the specific etiology, time of onset, and ensuing complications. After ischemic stroke, prophylactic treatment is not generally recommended, and after intracerebral hemorrhage treatment is recommended only after a few weeks. After subarachnoid hemorrhage, prophylactic treatment beyond discharge is also not recommended. Although there is no reason to believe that late seizures after severe head trauma cannot be prevented with prophylactic treatment, such an approach may be useful during the first week after the injury. Physicians, however, have to individualize the treatment to the critical patient after stroke or trauma based on the presence of additional factors that increase the risk for seizures, including structural cortical injuries and medications used in critical illness with epileptogenic potential. A general therapeutic scheme for seizures in the intensive care unit and the role newer antiepileptic drugs can play are also presented in this review.

Brain Injuries↗

PubMed1987

Asymmetric rotational (circling) behavior, a dopamine-related asymmetry: preliminary findings in unmedicated and never-medicated schizophrenic patients.

Circling behavior is one of the best understood behaviors in animals. It is, for the most part, dopaminergically mediated and related to asymmetry in dopaminergic activity between the left and right basal ganglia or left and right frontal cortex. As a rule, animals rotate toward the hemisphere with lower striatal dopaminergic activity. A direct technique to find human analogs of circling behavior was not available. We have developed an automated rotometer with which we can apply the circling rodent model to humans. Left-prone circling behavior (neglect of right-sided turning) was found in 10 unmedicated schizophrenic patients, whereas 85 normal controls demonstrated almost equal right and left turning. These preliminary results may suggest the presence of a dopaminergic asymmetry in some unmedicated schizophrenic patients; that is, right anterior subcortical or cortical structures of the brain may manifest a relative dopaminergic overactivity compared to left anterior structures in at least some unmedicated patients with schizophrenia.

Adult↗

PubMed1991

Limbic/mesolimbic connections and the pathogenesis of schizophrenia.

The development of models of the pathogenesis of neuropsychiatric diseases that build on recent advances in chemical neuroanatomy will help to guide future research. The interconnections among limbic, basal ganglia, and cortical structures are used to form the basis of a hypothesis of the pathogenesis of schizophrenia. The adaptive capacity of subcortical dopamine systems is advanced as an explanation of the many states of the disease.

Humans↗

PubMed1983

Non-random distribution of blood vessels in the posterior region of the rat somatosensory cortex.

The quantitative distribution of blood vessels in the barrel region of somatosensory cortex of the rat was studied to determine the relationship of the vascular pattern to a functionally specialized cortical structure. Blood vessels were found to arborize in layers III and IV and to decrease in number toward layers I and VI, creating a spindle-shaped pattern through the cortex. The density of blood vessels was greater in the barrel core versus septal regions of layer IV. The distribution pattern of blood vessels within the barrel region was remarkably non-random and constant even between animals. The pattern was consistent enough to form a reliable set of landmarks with which to identify a specific barrel from light- to electron-microscopy transition.

Animals↗

PubMed1984

Distribution of immunoreactive dynorphin B in discrete areas of the rat brain and spinal cord.

The distribution of immunoreactive (ir)-dynorphin B in 101 microdissected rat brain and spinal cord regions was determined using a specific radioimmunoassay. The highest concentration of dynorphin B in brain was found in the substantia nigra (1106.2 fmol/mg protein). Very high concentrations of ir-dynorphin B (greater than 400 fmol/mg protein) were also found in the lateral preoptic area, parabrachial nuclei and globus pallidus. Relatively high concentrations of ir-dynorphin B (250-400 fmol/mg protein) were found in 19 nuclei, including the periaqueductal gray matter, anterior hypothalamic nucleus, median eminence, nucleus accumbens and hippocampus. Moderate levels of the peptide (between 100 and 250 fmol/mg protein) were found in 42 brain nuclei such as the perifornical nucleus, nucleus of the diagonal band, medial forebrain bundle, and dorsal premamillary nucleus. Low concentrations of ir-dynorphin B (less than 100 fmol/mg protein) were found in 28 brain areas, e.g. cerebral cortical structures (parietal, cingulate, frontal), claustrum, olfactory bulb, lateral and periventricular thalamic nuclei. The cerebellar cortex has the lowest dynorphin B concentration (53.7 fmol/mg protein). Spinal cord segments exhibit low or moderate (cervical segment) levels of the peptide. The neurointermediate lobe of the pituitary gland is extremely rich in ir-dynorphin B (11,047.1 fmol/mg protein).

Animals↗

PubMed1985

Distribution of immunoreactive metorphamide (adrenorphin) in discrete regions of the rat brain: comparison with Met-enkephalin-Arg6-Gly7-Leu8.

The distribution of immunoreactive (ir)-metorphamide (adrenorphin) in 101 microdissected rat brain and spinal cord regions was determined using a highly specific radioimmunoassay. The highest concentration of metorphamide in brain was found in globus pallidus (280.1 fmol/mg protein). High concentrations of ir-metorphamide (greater than 120 fmol/mg protein) were found in 9 nuclei, including central amygdaloid nucleus, lateral preoptic area, anterior hypothalamic nucleus, hypothalamic paraventricular nucleus, interpeduncular nucleus, periaqueductal grey matter and nucleus of the solitary tract. Moderate concentrations of the peptide (between 60 and 120 fmol/mg protein) were found in 47 brain nuclei such as nucleus accumbens, bed nucleus of stria terminalis, several septal and amygdaloid nuclei, most of the hypothalamic nuclei, ventral tegmental area, red nucleus, raphe nuclei, lateral reticular nucleus, area postrema and others. Low concentrations or ir-metorphamide (less than 60 fmol/mg protein) were measured in 41 nuclei, e.g., cortical structures, hippocampus, caudate nucleus, thalamic nuclei, supraoptic nucleus, substantia nigra, vestibular nuclei, cerebellum (nuclei and cortex). The olfactory bulb has the lowest metorphamide concentration (5.8 fmol/mg protein). Spinal cord segments exhibit very low peptide concentrations.

Animals↗

PubMed1986

The effect of limbic and extralimbic electrical stimulations upon prolactin secretion in humans.

The effect that extra-hypothalamic regions of the brain have upon prolactin secretion in humans was evaluated by performing electrical stimulations. Thirty-nine stimulations were performed, 22 to basolateral amygdala, 12 to hippocampus and 5 to orbitofrontal, supplementary motor and cingulate cortex. Only two stimulations causing high-frequency widespread limbic afterdischarges were followed by significant prolactin elevation. Four low-frequency afterdischarges involving amygdala and anterior hippocampus, one amygdala stimulus-dependent discharge and 19 amygdala, 8 hippocampal and 5 frontal sub-afterdischarge threshold stimulations had no prolactin elevation. These results fail to replicate earlier studies. We suggest that there is no evidence that the amygdala regulates serum prolactin within physiologic ranges, but that the regulation of prolactin may depend primarily upon other sub-cortical structures.

Amygdala↗

PubMed1992

Changes in neurotransmitter parameters in the brain induced by L-cysteine injections in the young rat.

A single subcutaneous injection of L-cysteine (1.2 mg/g body wt.) to 4-day-old rats leads to atrophy of the brains examined 27-31 days later. The brains could be separated into two groups (type 1 and 2) on account of the degree of atrophy. Type-1 lesion, with a brain weight reduction of 20%, was dominated by a severe reduction in high-affinity uptake of L-glutamate in CNS regions receiving corticofugal fibers such as thalamus and striatum. Glutamate decarboxylase was only reduced in cortical structures. In type-2 lesion, with a severe brain atrophy of about 50%, high-affinity glutamate uptake was further reduced and there was a more pronounced reduction in glutamate decarboxylase activity in several brain regions. Cholinergic neurons were less affected by the lesion and the levels of choline acetyltransferase showed a relative increase in brain regions which partly compensated for their reduction in size.

Acetylcholine↗

PubMed1993

Immunohistochemical detection of raf protein kinase in cerebral cortical areas of adult guinea pigs and rats.

The raf protooncogenes are the cellular counterparts of the v-raf oncogene expressed by a murine sarcoma virus. The raf protooncogenes encode cytoplasmic serine/threonine-specific protein kinases which can be activated from different growth factor receptors by phosphorylation. The mRNAs of raf protooncogenes are found in a large variety of normal adult tissues, including the central nervous system. As concerns the distribution and localization of their protein products (the raf kinases), very few data are to be found in the literature. This is the first detailed description of their light microscopic localization in neocortical and allocortical areas of rodents. Preembedding immunohistochemical studies were performed on vibratome sections from the brains of adult guinea pigs and albino rats. The localizations of two isoenzymes, raf-1 kinase and B-raf kinase, were studied with the help of isoenzyme-specific polyclonal antibodies. Both of the antibodies detected raf protein-like immunoreactivity in many neurons and scattered glial cells of the sensory neocortex, and the cingular, pyriform, perirhinal and entorhinal allocortical areas. Pyramidal and non-pyramidal cells of Ammon's horn, granule cells of the dentate fascia and the large neurons in the hilar region were immunoreactive, too. The findings indicated that B-raf protein kinase and raf-1 kinase are present almost ubiquitously in the neurons of the investigated cortical structures. The intensity of staining obtained with serial dilutions of the antibodies indicated that the cytoplasmic concentration of B-raf kinase is tended to be higher than that of raf-1 kinase. The present findings suggested that the raf kinases are localized in postsynaptic structures, mainly in dendrites and cell bodies. Their cytosolic localization and their ability to undergo intracellular translocation during activation and phosphorylation raise the possibility that they play a pivotal role in the intracellular signaling of neurons.

Amino Acid Sequence↗

PubMed1994

Polysensory evoked potentials in rat parietotemporal cortex: combined auditory and somatosensory responses.

A 64 channel microelectrode array was used to map auditory evoked potentials (AEP), somatosensory evoked potentials (SEP) as well as combined auditory and somatosensory evoked potentials (ASEP) from a 7 x 7 mm2 area in rat parietotemporal neocortex. Cytochrome oxidase (CO) stained sections of layer IV were obtained in the same animals to provide anatomical information underlying epicortical field potentials. Epicortical responses evoked by click or vibrissa stimuli replicated earlier findings from our laboratory, and appeared as a family of waveforms centered on primary auditory (AI) or somatosensory (SI) cortical areas as determined from CO histology. Selective microinjections of HRP to AI and SI further confirmed their specific sensory relay nuclei in the thalamus. A small polysensory area between AI and SI, responded uniquely with an enhanced negative sharp wave to combined auditory and somatosensory stimuli. HRP retrograde labeling revealed that the thalamocortical projections to this area were from the posterior nuclear group (Po) and medial division of the medial geniculate (MGm). These data establish close relationships between epicortical AEP, SEP, and especially ASEP and corresponding cortical structures and thalamocortical projections. The neurogenesis of unimodal and polysensory evoked potentials is discussed in terms of specific and non-specific systems.

Acoustic Stimulation↗