Journal of neurophysiology
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Hypocretin (orexin)-containing neurons in the hypothalamus, which have been implicated in the pathology of narcolepsy, project to nuclei in the brain stem reticular formation that are involved in the control of the behavioral states of sleep and wakefulness. Among these nuclei is the nucleus pontis oralis (NPO). Consequently, the present study was undertaken to determine if the hypocretinergic system provides regulatory input to neurons in the NPO with respect to the generation of the states of sleep and wakefulness. ⋯ In this preparation, the application of hypocretin-1 resulted in the depolarization of NPO neurons, an increase in the frequency of their discharge and an increase in their excitability. These latter data represent the first description of the in vivo action of hypocretin on intracellularly recorded neuronal activity and provide evidence that the active sleep-inducing effects of hypocretin are due to a direct excitatory action on NPO neurons. Therefore we suggest that hypocretinergic processes in the NPO may play a role in the generation of active sleep, particularly muscle atonia and therefore are likely to be involved in the pathology of narcolepsy.
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Spaced training is generally more effective than massed training for learning and memory, but the molecular mechanisms underlying this trial spacing effect remain poorly characterized. One potential molecular basis for the trial spacing effect is the differential modulation, by distinct temporal patterns of neuronal activity, of protein synthesis-dependent processes that contribute to the expression of specific forms of synaptic plasticity in the mammalian brain. Long-term potentiation (LTP) is a type of synaptic modification that may be important for certain forms of memory storage in the mammalian brain. ⋯ Temporally spaced behavioral training improved long-term memory for contextual but not for cued fear conditioning, and this enhancement of memory for contextual fear was also protein synthesis dependent. Our data reveal that altering the temporal spacing of synaptic stimulation and behavioral training improved hippocampal LTP and enhanced contextual long-term memory. From a broad perspective, these results suggest that the recruitment of protein synthesis-dependent processes important for long-term memory and for long-lasting forms of LTP can be modulated by the temporal profiles of behavioral training and synaptic stimulation.
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Changes in the biophysical properties of AMPA-type glutamate receptors have been proposed to mediate the expression of long-term potentiation (LTP). The present study tested if, as predicted from this hypothesis, AMPA receptor modulators differentially affect potentiated versus control synaptic currents. Whole cell recordings were collected from CA1 pyramidal neurons in hippocampal slices from adult rats. ⋯ Additionally, there was no significant change in paired-pulse facilitation in the presence of CTZ, indicating that presynaptic effects of the drug were negligible. These findings provide new evidence that LTP modifies AMPA receptor kinetics. Candidates for the changes responsible for the observed effects of LTP were evaluated using a model of AMPA receptor kinetics; a simple increase in the channel opening rate provided the most satisfactory match with the LTP data.
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We investigated neural coding of sinusoidally modulated tones (sAM and sFM) in the primary auditory cortex (A1) of awake marmoset monkeys, demonstrating that there are systematic cortical representations of embedded temporal features that are based on both average discharge rate and stimulus-synchronized discharge patterns. The rate-representation appears to be coded alongside the stimulus-synchronized discharges, such that the auditory cortex has access to both rate and temporal representations of the stimulus at high and low frequencies, respectively. Furthermore, we showed that individual auditory cortical neurons, as well as populations of neurons, have common features in their responses to both sAM and sFM stimuli. ⋯ The discharge synchrony-based best modulation frequency (tBMF) was typically lower than the rBMF measured from the same neuron. The distribution of rBMF over the population of neurons was approximately one octave higher than the distribution of tBMF. 4) There was a high degree of similarity between cortical responses to sAM and sFM stimuli that was reflected in both discharge rate- or synchrony-based response measures. 5) Inhibition appeared to be a contributing factor in limiting responses at modulation frequencies above the rBMF of a neuron. And 6) neurons with shorter response latencies tended to have higher tBMF and maximum discharge synchrony frequency than those with longer response latencies. rBMF was not significantly correlated with the minimum response latency.
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Descending inhibitory and facilitatory influences from the rostroventral medulla (RVM) on responses of lumbosacral spinal neurons to noxious colorectal distension (CRD, 80 mmHg, 20 s) were studied. At 25 sites in the RVM, electrical stimulation produced biphasic effects, facilitating responses of spinal neurons to CRD at lesser intensities of stimulation (5-25 microA) and inhibiting responses of the same neurons at greater intensities of stimulation (50-100 microA). At 38 other sites in the RVM, electrical stimulation produced only intensity-dependent inhibition of neuron responses to CRD. ⋯ Microinjection of glutamate into the RVM at a low dose (5 nmoles) facilitated responses of spinal neurons to CRD and inhibited responses of the same neurons at a greater dose (50 nmoles). In some experiments, microinjection of lidocaine (0.5 microl of 4% solution) or the neurotoxin ibotenic acid (0.5 microl, 10 microg) into the RVM produced reversible or long-lasting, respectively, decreases in spontaneous activity and responses of spinal neurons to CRD. These results reveal that spinal visceral nociceptive transmission is subject to a tonic descending excitatory influence from the RVM and that descending modulatory effects from the RVM on visceral nociceptive transmission are qualitatively similar to modulation of cutaneous nociceptive transmission.