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Seizures, particularly multiple episodes and/or status epilepticus (SE) are prevalent in pediatric patients. Pediatric SE is associated with brain changes that have been hypothesized to contribute to the onset of temporal lobe epi...
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Seizures, particularly multiple episodes and/or status epilepticus (SE) are prevalent in pediatric patients. Pediatric SE is associated with brain changes that have been hypothesized to contribute to the onset of temporal lobe epilepsy (TLE). In order to gain insight into the effects of seizures on the immature brain and the risk for later TLE, we have developed a model of limbic SE in the pigtailed macaque monkey. In separate studies, bicuculline methiodide or a bicuculline 'cocktail' was infused into three regions of the brain (area tempestas, hippocampus, entorhinal cortex) to induce seizures. Measures included MRI, electrophysiology, behavior and morphology. Our results suggest that monkey models of SE may provide useful tools for understanding the effects of prolonged seizures during infancy and the origins of TLE in humans. Copyright Copyright 1999 S. Karger AG, Basel
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Compared with control rats, SST-IR and SS mRNA-positive neurons in hypothalamic periventricular nucleus(PeV), paraventricular nucleus(PVN), and ar- cuate nucleus(ARC)increased after acute hypobaric hy- poxia for 6 h(P < 0.01), and these effects were markedly inhibited by AP-V (10μg, icv), a highly se- lective N-methyl-D-aspartate(NMDA)receptro antago- nist, whereas were strongly enhanced by bicuculine(1.5 mg.kg~-1, ip)a gamma-aminobutyric acid(GABA_A) receptor antagonist. SST possibly Participates in acute hypoxic reaction in hypothalamus, Furthermore, glutamate and GABA can affect somatostatin Release and synthesis in hypothalamus through NMDA and GABA_A receptors respectively....
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Compared with control rats, SST-IR and SS mRNA-positive neurons in hypothalamic periventricular nucleus(PeV), paraventricular nucleus(PVN), and ar- cuate nucleus(ARC)increased after acute hypobaric hy- poxia for 6 h(P < 0.01), and these effects were markedly inhibited by AP-V (10μg, icv), a highly se- lective N-methyl-D-aspartate(NMDA)receptro antago- nist, whereas were strongly enhanced by bicuculine(1.5 mg.kg~-1, ip)a gamma-aminobutyric acid(GABA_A) receptor antagonist. SST possibly Participates in acute hypoxic reaction in hypothalamus, Furthermore, glutamate and GABA can affect somatostatin Release and synthesis in hypothalamus through NMDA and GABA_A receptors respectively.
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Intrinsic signal optical imaging was used to record the changes in light transmittance evoked by electrical stimulation in slices prepared from sensorimotor cortex of young adult rats. The spatial characteristics of the optical si...
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Intrinsic signal optical imaging was used to record the changes in light transmittance evoked by electrical stimulation in slices prepared from sensorimotor cortex of young adult rats. The spatial characteristics of the optical signal evoked by stimulation of layer II/III, IV, V, or VI were clearly different. Layer IV and V stimulation elicited a radially-oriented region of increased light transmittance which was "hourglass" shaped: its tangential extent was greatest in layers II/III and layer V, and least in layer IV. Layer VI stimulation also elicited a radially-oriented signal but the tangential extent of this signal was the same across layers II-VI--that is, it was column-shaped. Upper layer stimulation produced a signal whose tangential extent was much greater in the upper layers than its radial extent to the deeper layers. The spatial form of the stimulus-evoked intrinsic signal was not dependent on the cytoarchitectonic area in which it was elicited. The tangential and radial distribution of the signal evoked by stimulation of different layers appears to reflect the connectivity of cortex, particularly the horizontal connectivity present in layers II/III, V, and VI, and the interlaminar connections that exist between layers II/III and V and from layers VI to IV. The spatial characteristics of the intrinsic signal were independent of the strength of stimulation used. The idea that inhibitory mechanisms restrict the tangential extent of the signal was evaluated in experiments in which the intrinsic signal was recorded before and after the addition of 10 microM bicuculline methiodide. In all slices studied in this way (n = 12), bicuculline methiodide drastically increased the tangential extent of the signal. In 4/12 slices, the tangential spread of the signal was asymmetric with respect to the stimulus site. Asymmetric spread of the signal occurred for both layer V and layer VI stimulation and, in 2/4 of those cases, could be attributed to a cytoarchitectonic border whose presence appeared to restrict the spread of the signal across the border. Although increasing stimulation strength did not change the spatial characteristics of the radially-oriented signal evoked by layer V or VI stimulation, at maximal stimulus intensity the signal evoked from these layers was often accompanied by a band of decreased light transmittance in the most superficial layers (layers I and II). It is concluded that in vitro intrinsic optical signal imaging allows one to image a response attributable to activation of local subsets of cortical connections. In addition, the opposite effects of high-intensity deep layer stimulation on the superficial layers vs layers III-VI of the same column raise the possibility that the most superficial layers may respond differently to repetitive input drive than the rest of the cortical column.
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Rationale Tiagabine is an anticonvulsant drug which may also have sleep-enhancing properties. It acts by inhibiting reuptake at the gamma-aminobutyric acid (GABA) transporter (GAT-1).
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Key points ? Initiation of pathological synchronous events such as epileptic spikes and seizures is linked to the hyperexcitability of the neuronal network in both humans and animals. ? In the present study, we show that epileptif...
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Key points ? Initiation of pathological synchronous events such as epileptic spikes and seizures is linked to the hyperexcitability of the neuronal network in both humans and animals. ? In the present study, we show that epileptiform interictal‐like spikes and seizures emerged in human neocortical slices by blocking GABA A receptors, following the disappearance of the spontaneously occurring synchronous population activity. ? Large variability of temporally and spatially simple and complex spikes was generated by tissue from epileptic patients, whereas only simple events appeared in samples from non‐epileptic patients. ? Physiological population activity was associated with a moderate level of principal cell and interneuron firing, with a slight dominance of excitatory neuronal activity, whereas epileptiform events were mainly initiated by the synchronous and intense discharge of inhibitory cells. ? These results help us to understand the role of excitatory and inhibitory neurons in synchrony‐generating mechanisms, in both epileptic and non‐epileptic conditions. Abstract Understanding the role of different neuron types in synchrony generation is crucial for developing new therapies aiming to prevent hypersynchronous events such as epileptic seizures. Paroxysmal activity was linked to hyperexcitability and to bursting behaviour of pyramidal cells in animals. Human data suggested a leading role of either principal cells or interneurons, depending on the seizure morphology. In the present study, we aimed to uncover the role of excitatory and inhibitory processes in synchrony generation by analysing the activity of clustered single neurons during physiological and epileptiform synchronies in human neocortical slices. Spontaneous population activity was detected with a 24‐channel laminar microelectrode in tissue derived from patients with or without preoperative clinical manifestations of epilepsy. This population activity disappeared by blocking GABA A receptors, and several variations of spatially and temporally simple or complex interictal‐like spikes emerged in epileptic tissue, whereas peritumoural slices generated only simple spikes. Around one‐half of the clustered neurons participated with an elevated firing rate in physiological synchronies with a slight dominance of excitatory cells. By contrast, more than 90% of the neurons contributed to interictal‐like spikes and seizures, and an intense and synchronous discharge of inhibitory neurons was associated with the start of these events. Intrinsically bursting principal cells fired later than other neurons. Our data suggest that a balanced excitation and inhibition characterized physiological synchronies, whereas disinhibition‐induced epileptiform events were initiated mainly by non‐synaptically synchronized inhibitory neurons. Our results further highlight the differences between humans and animal models, and between in vivo and (pharmacologically manipulated) in vitro conditions.
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It is widely appreciated that neuronal networks exhibit patterns of bursting and synchrony that are not captured by simple measures such as average spike rate. These patterns can encode information or represent pathological behavi...
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It is widely appreciated that neuronal networks exhibit patterns of bursting and synchrony that are not captured by simple measures such as average spike rate. These patterns can encode information or represent pathological behavior such as seizures. However, methods for quantifying bursting and synchrony are not agreed upon and can be confounded with spike rate measures. Previous validation has largely relied on in silico networks and single experimental conditions. How published measures of bursting and synchrony perform when applied to biological networks of varied average spike rate and subjected to varied experimental challenges is unclear. In multielectrode array recordings of network activity, we found that two mechanistically distinct drugs, cyclothiazide and bicuculline, produced equivalent increases in average spike rate but differed in bursting and synchrony. We applied several measures of bursting to the recordings (2 threshold interval methods and a surprise-based method) and found that a measure based on an average critical interval, adjusted for the array-wide spike rate, performed best in quantifying differential drug effects. To quantify synchrony, we compared a coefficient of variation-based measure, the recently proposed spike time tiling coefficient, the SPIKE-distance measure, and a global synchrony index. The spike time tiling coefficient, the SPIKE-distance measure, and the global synchrony index all captured a difference between drugs with the best performance exhibited by the global synchrony index. In summary, our exploration should aid other investigators by highlighting strengths and limitations of current methods.
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Both hypoactivity and hyperactivity in the amygdala are associated with perturbations in social behavior. While >60 years of experimental manipulations of the amygdala in animal models have shown that amygdala is critical for soci...
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Both hypoactivity and hyperactivity in the amygdala are associated with perturbations in social behavior. While >60 years of experimental manipulations of the amygdala in animal models have shown that amygdala is critical for social behavior, many of these studies contradict one another. Moreover, several questions remain unaddressed. (1) What effect does activation of amygdala have on social behavior? (2) What is the effect of transient silencing, rather than permanent damage? (3) Is there a dissociation between the roles of the central (CeA) and basolateral amygdala (BLA) in regulating social behavior? (4) Can the prosocial effects of amygdala manipulations be explained by anxiolytic effects? We focally manipulated activity within the CeA or BLA in macaques by intracerebral microinjection of muscimol (to inactivate) or bicuculline (to activate) to these amygdaloid subregions. Social interactions were observed in pairs of highly familiar monkeys. We compared these effects to those achieved with systemic diazepam. Activation of the BLA but not CeA suppressed social behavior. Inhibition of either structure increased social behavior, although the effect was greater following inhibition of the BLA. Systemic diazepam was without effect. These studies, which are the first to bidirectionally manipulate the primate amygdala for effects on social behavior, revealed that (1) the amygdala, as a critical regulator of the social network, is bidirectionally sensitive to perturbations in activity, and (2) increased sociability after amygdala inactivation cannot be solely explained by decreased fear.
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The role of GABAergic inhibition in orientation and direction selectivity has been investigated with the GABAA-Blocker bicuculline in the cat visual cortex, and results indicated a region specific difference of functional contribu...
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The role of GABAergic inhibition in orientation and direction selectivity has been investigated with the GABAA-Blocker bicuculline in the cat visual cortex, and results indicated a region specific difference of functional contributions of GABAergic inhibition in areas 17 and 18. In area 17 inhibition appeared mainly involved in sculpturing orientation and direction tuning, while in area 18 inhibition seemed more closely associated with temporal receptive field properties. However, different types of stimuli were used to test areas 17 and 18 and further studies performed in area 17 suggested an important influence of the stimulus type (single light bars vs. moving gratings) on the evoked responses (transient vs. sustained) and inhibitory mechanisms (GABAA vs. GABAB) which in turn might be more decisive for the specific results than the cortical region. To insert the missing link in this chain of arguments it was necessary to study GABAergic inhibition in area 18 with moving light bars, which has not been done so far. Therefore, in the present study we investigated area 18 cells responding to oriented moving light bars with extracellular recordings and reversible microiontophoretic blockade of GABAergig inhibition with bicuculline methiodide. The majority of neurons was characterized by a pronounced orientation specificity and variable degrees of direction selectivity. GABAAergic inhibition significantly influenced preferred orientation and preferred direction in area 18. During the action of bicuculline orientation tuning width increased and orientation and direction selectivity indices decreased. Our results obtained in area 18 with moving bar stimuli, although in the proportion of affected cells similar to those described in area 17, quantitatively matched the findings for direction and orientation specificity obtained with moving gratings in area 18. Accordingly, stimulus type is not decisive in area 18 and the GABAA dependent, inhibitory intracortical computations involved in orientation specificity are indeed region-specific and in comparison to area 17 less effective in area 18. Keywords Visual system - Inhibition - Bicuculline - Microiontophoresis
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Previous studies have shown that infusion of a GABA(A) receptor antagonist, such as bicuculline (bic), into the ventral (pallidum VP) of rats elicits vigorous ingestion in sated subjects and abnormal pivoting movements. Here, we a...
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Previous studies have shown that infusion of a GABA(A) receptor antagonist, such as bicuculline (bic), into the ventral (pallidum VP) of rats elicits vigorous ingestion in sated subjects and abnormal pivoting movements. Here, we assessed if the ingestive effects generalize to the lateral preoptic area (LPO) and tested both effects for modulation by dopamine receptor signaling. Groups of rats received injections of the dopamine D2 receptor antagonist, haloperidol (hal), the D1 antagonist, SCH-23390 (SCH), or vehicle (veh) followed by infusions of bic or veh into the VP or LPO. Ingestion effects were not observed following LPO bic infusions. Compulsive ingestion associated with VP activation was attenuated by hal, but not SCH. VP bic-elicited pivoting was attenuated by neither hal, nor SCH.
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Highlights ? Stress before fear learning prevents reconsolidation interference in canulated rats. ? MDZ intra-BLA before stress prevents the resistance to memory interference. ? BIC intra-BLA before fear learning prevents the inte...
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Highlights ? Stress before fear learning prevents reconsolidation interference in canulated rats. ? MDZ intra-BLA before stress prevents the resistance to memory interference. ? BIC intra-BLA before fear learning prevents the interfering effect of MDZ. ? DCS before retrieval restores the vulnerability in BIC-induced resistant memory. Abstract It is well known that stress can affect mnemonic processes. In particular, stress before contextual fear conditioning induces a memory which exhibits resistance to being interfered with by Midazolam (MDZ) when applied after memory retrieval. Moreover, stress exposure strongly affects GABAergic transmission within the Basolateral Amygdala Complex (BLA), a brain structure critically involved in fear memory processing. The present study evaluated the involvement of GABAergic signaling within the BLA on the induction of resistance to memory reconsolidation interference. Results showed that MDZ administered intra-BLA before stress prevented the induction of resistance to the interfering effect of systemic administration of both MDZ and Propranolol on fear memory reconsolidation, when both applied after memory retrieval. The blockade of amygdala GABA-A receptors by the antagonist Bicuculline (BIC) before memory encoding induced resistance to interference by post-recall MDZ administration, similarly to that observed with stress exposure. Additionally, the systemic administration of d -cycloserine, a positive allosteric modulator of NMDA receptor, reverted the BIC-induced resistance to the MDZ interfering effect, in the same manner as that reported with stress-induced resistance. In summary, these results suggest that the GABAergic signaling in the BLA at the moment of memory encoding is determinant for the induction of fear memory resistance to the onset of the labilization/reconsolidation process.
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