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Although gap junctions were first demonstrated in the mammalian brain about 30 years ago, the distribution and role of electrical synapses have remained elusive. A series of recent reports has demonstrated that inhibitory interneurons in the cerebral cortex, thalamus, striatum and cerebellum are extensively interconnected by electrical synapses. Investigators have used paired recordings to reveal directly the presence of electrical synapses among identified cell types. These studies indicate that electrical coupling is a fundamental feature of local inhibitory circuits and suggest that electrical synapses define functionally diverse networks of GABA-releasing interneurons. Here, we discuss these results, their possible functional significance and the insights into neuronal circuit organization that have emerged from them.

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The temporal pattern and relative timing of action potentials among neocortical neurons may carry important information. However, how cortical circuits detect or generate coherent activity remains unclear. Using paired recordings in rat neocortical slices, we found that the firing of fast-spiking cells can reflect the spiking pattern of single-axon pyramidal inputs. Moreover, this property allowed groups of fast-spiking cells interconnected by electrical and gamma-aminobutyric acid (GABA)-releasing (GABAergic) synapses to detect the relative timing of their excitatory inputs. These results indicate that networks of fast-spiking cells may play a role in the detection and promotion of synchronous activity within the neocortex.

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Taurine induces a long-lasting potentiation of excitatory synaptic potentials due to the enhancement of both synaptic efficacy and axon excitability in the CA1 area of rat hippocampal slices. In this study, we characterized the role of Ca2+ in the generation of these long-lasting taurine effects. Taurine perfusion in a free-Ca2+ medium did not induce changes in either field excitatory synaptic potentials (fEPSP) slope or fiber volley (FV) amplitude. Intracellular recordings with a micropipette filled with the Ca2+ chelator BAPTA, prevented the EPSP potentiation induced by taurine in the impaled cell, whereas a long-lasting potentiation of the simultaneously recorded fEPSP was obtained. The depletion of intracellular Ca2+ stores by thapsigargin (1 microM), an inhibitor of endosomal Ca2+-ATPase, transformed the taurine-induced potentiation into a transitory process that declined to basal values after taurine withdrawal. Taurine-induced potentiation was not significantly affected by kynurenate (glutamate receptor antagonist), or nifedipine (high-voltage-activated Ca2+ channel antagonist). But, the presence of nickel (50 microM), an antagonist of low-voltage-activated Ca2+ channel, inhibited the taurine-induced potentiation, indicating that Ca2+ influx through this type of Ca2+ channels could account for the Ca2+ requirement of the taurine-induced potentiation. Occlusion experiments between tetanus-induced long-term potentiation (LTP) and taurine-induced potentiation indicate that both processes share some common mechanisms during the maintenance period.

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High-frequency activity produces transient depression at many synapses but also, as recently demonstrated, may accelerate the recovery from use-dependent depression. We have examined the possible consequences of this synaptic mechanism in neocortical excitatory synapses by recording simultaneously from presynaptic pyramidal neurons and their postsynaptic targets. Brief bursts of high-frequency spikes produced a strong depression of the amplitude of unitary excitatory postsynaptic currents (uEPSCs). However, when burst firing was combined with low-frequency ongoing activity, we found that the strong synaptic depression was followed by a transient rebound of synaptic strength. This rebound overshot the low-frequency baseline values and lasted 1-2 s. These results suggest that in the presence of ongoing activity, neocortical synapses may functionally facilitate following burst firing.

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Encoding of information in the cortex is thought to depend on synchronous firing of cortical neurons. Inhibitory neurons are known to be critical in the coordination of cortical activity, but how interaction among inhibitory cells promotes synchrony is not well understood. To address this issue directly, we have recorded simultaneously from pairs of fast-spiking (FS) cells, a type of gamma-aminobutyric acid (GABA)-containing neocortical interneuron. Here we report a high occurrence of electrical coupling among FS cells. Electrical synapses were not found among pyramidal neurons or between FS cells and other cortical cells. Some FS cells were interconnected by both electrical and GABAergic synapses. We show that communication through electrical synapses allows excitatory signalling among inhibitory cells and promotes their synchronous spiking. These results indicate that electrical synapses establish a network of fast-spiking cells in the neocortex which may play a key role in coordinating cortical activity.

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Oxytocin (OT) and vasopressin (VP) hormone release from neurohypophysial terminals is controlled by the firing pattern of neurosecretory cells located in the hypothalamic supraoptic (SON) and paraventricular nuclei. Although glutamate is a key modulator of the electrical activity of both OT and VP neurons, a differential contribution of AMPA receptors (AMPARs) and NMDA receptors (NMDARs) has been proposed to mediate glutamatergic influences on these neurons. In the present study we examined the distribution and functional properties of synaptic currents mediated by AMPARs and NMDARs in immunoidentified SON neurons. Our results suggest that the properties of AMPA-mediated currents in SON neurons are controlled in a cell type-specific manner. OT neurons displayed AMPA-mediated miniature EPSCs (mEPSCs) with larger amplitude and faster decay kinetics than VP neurons. Furthermore, a peak-scaled nonstationary noise analysis of mEPSCs revealed a larger estimated single-channel conductance of AMPARs expressed in OT neurons. High-frequency summation of AMPA-mediated excitatory postsynaptic potentials was smaller in OT neurons. In both cell types, AMPA-mediated synaptic currents showed inward rectification, which was more pronounced in OT neurons, and displayed Ca2+ permeability. On the other hand, NMDA-mediated mEPSCs of both cell types had similar amplitude and kinetic properties. The cell type-specific expression of functionally different AMPARs can contribute to the adoption of different firing patterns by these neuroendocrine neurons in response to physiological stimuli.

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The stability of cortical neuron activity in vivo suggests that the firing rates of both excitatory and inhibitory neurons are dynamically adjusted. Using dual recordings from excitatory pyramidal neurons and inhibitory fast-spiking neurons in neocortical slices, we report that sustained activation by trains of several hundred presynaptic spikes resulted in much stronger depression of synaptic currents at excitatory synapses than at inhibitory ones. The steady-state synaptic depression was frequency dependent and reflected presynaptic function. These results suggest that inhibitory terminals of fast-spiking cells are better equipped to support prolonged transmitter release at a high frequency compared with excitatory ones. This difference in frequency-dependent depression could produce a relative increase in the impact of inhibition during periods of high global activity and promote the stability of cortical circuits.

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Rapid applications of GABA (from 10 microM to 10 mM) to outside-out patches were used to study the role that the kinetic properties of GABAA receptors play in determining the time course of IPSCs in neocortical pyramidal neurons. Currents induced by rapid applications of brief (1 msec) pulses of GABA (1 mM) showed a biexponential decay phase that seems to involve the entry of GABAA receptors into desensitized states. This conclusion is based on the similar fast decay kinetics of the response to brief and prolonged pulses of GABA and on the correlation between the degree of paired-pulse depression and the decay rate of the currents induced by brief pulses. Under nonequilibrium conditions we found that the concentration-response curve of pyramidal GABAA receptors has an EC50 of 185 microM (GABA pulse of 1 msec). The decay time course of the patch currents in response to brief applications of GABA was insensitive to agonist concentrations at the range from 50 microM to 10 mM. Faster decay rates were observed only in response to pulses of 10 microM GABA. These data are compatible with the suggestion that briefer openings derive from a monoliganded state and that these are negligible when receptor activation is >2%. Assuming that GABA transients at neocortical synapses are fast, a several millimolar GABA concentration would be needed to saturate the postsynaptic GABAA receptors.

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The physiological role of taurine, one of the most abundant free amino acids in the mammalian brain, is still poorly understood. We have found that bath application of the amino acid taurine induces two opposite actions on field excitatory synaptic potentials (fEPSP) recorded in the CA1 area of hippocampal slices: a decrease in fEPSP slope prevented by GABAA antagonists, and a long-lasting potentiation of fEPSP independent of GABAA or NMDA receptor activation. Two long-lasting processes account for this taurine-induced potentiation: (1) an increase in synaptic efficacy that is accompanied neither by modifications in the basic postsynaptic membrane electrical properties nor by those presynaptic changes involved in fEPSP paired-pulse facilitation; and (2) an increase in the axon excitability revealed by a reduction on the threshold for antidromic action potential activation. In addition, taurine perfusion also induces a long-lasting increase in intracellularly recorded EPSPs and monosynaptically activated IPSPs. A number of experimental observations such as temperature dependence, extracellular Na+ concentration dependence, and saturation studies, although they are not unequivocally conclusive, suggest that the taurine uptake system is required for the taurine-induced fEPSP potentiation. Our data describe a new taurine action defined as a potentiation of synaptic transmission due in part to an increment in presynaptic axon excitability and in synaptic efficacy.

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It is known that the activation of N-methyl-D-aspartate (NMDA) receptors leads to an increase in extracellular taurine concentration in different brain regions. The mechanism that mediates this effect is not totally understood. In this study, rat hippocampal slices were used to determine the dependence of NMDA-induced taurine release on extracellular calcium and/or on calcium mobilization from intracellular stores. NMDA was administered through a microdialysis probe inserted into the slice, at the level of CA1 stratum radiatum, which was also used to collect amino acids from the extracellular space. Field potentials evoked by stimulation of the Schaffer collaterals and recorded in the stratum pyramidale of CA1 were used as a control of NMDA receptor activation. NMDA induced a marked increase in extracellular taurine levels and a decrease in field potential amplitude, and both effects were suppressed in the presence of MK-801, a blocker of the NMDA receptor-linked channel. Dantrolene, an inhibitor of calcium release from intracellular stores, partially inhibited the extracellular taurine increase, while 2-nitro-4-carboxyphenyl-N,N-diphenyl carbamate (NCDC), an inhibitor of phosphatidylinositol-specific phospholipase C activation, had no effect. Removal of extracellular calcium diminished, but did not abolish, the extracellular taurine increase caused by NMDA. The remaining taurine response was totally suppressed by dantrolene, and also by NCDC. These results demonstrate that the release of taurine induced by NMDA receptor activation is triggered by the increase in cytoplasmic calcium concentration. We suggest that, under physiological conditions, calcium influx provides the signal for NMDA-induced taurine release, which is amplified by calcium-dependent calcium mobilization from intracellular stores.(ABSTRACT TRUNCATED AT 250 WORDS)

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To assess the possible inhibitory action of nicotinamide adenine dinucleotides on the synaptic release of glutamate, electrophysiological and biochemical experiments were performed on rat hippocampal slices. Perfusion of adenosine, beta-nicotinamide adenine dinucleotide (NAD) or beta-nicotinamide adenine dinucleotide phosphate (NADP), reversibly inhibited the field excitatory postsynaptic potentials (fEPSP). Dose-response curves for their inhibitory action showed that these three substances had a similar potency in the range of concentrations from 0.1 microM to 100 microM. NADP and adenosine (100 microM) halved the K(+)-induced release of endogenous glutamate and aspartate, leaving gamma-amino-butyric acid (GABA) levels unchanged. 3-Isobutyl-1-methylxanthine (IBMX) 200 microM, an antagonist of the P1-purinoreceptors, antagonized the depressant effects of these coenzymes on both fEPSP and also on amino acid release. Based on these results we propose that nicotinamide adenine dinucleotides, similar to adenosine, inhibit excitatory synaptic transmission in the rat hippocampus by decreasing glutamate release from synaptic terminals.

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Isolated continuous lingual myoclonus is an exceptional entity, poorly documented and understood. A patient with a nonepileptic continuous rhythmical myoclonus, affecting the anterior portion of the tongue, as an independent involuntary disorder, is reported. Electromyography showed low frequency (2-4 Hz) bursts of genioglossus muscles activity. The EEG, visual, auditory and somatosensory evoked responses were normal. Imaging techniques like CT and MRI failed to reveal any brainstem or cerebellar lesion. Lingual myoclonus showed a very good response to sodium valproate.

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