Neuroscience
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Delta opioid receptors participate to the control of chronic pain and emotional responses. Recent data also identified their implication in spatial memory and drug-context associations pointing to a critical role of hippocampal delta receptors. We examined the distribution of delta receptor-expressing cells in the hippocampus using fluorescent knock-in mice that express a functional delta receptor fused at its carboxyterminus with the green fluorescent protein in place of the native receptor. ⋯ Fine mapping in the dorsal hippocampus confirmed that delta opioid receptors are mainly present in GABAergic neurons. Indeed, they are mostly expressed in parvalbumin-immunopositive neurons both in the Ammon's horn and dentate gyrus. These receptors, therefore, most likely participate in the dynamic regulation of hippocampal activity.
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Kainate receptors containing the GluK1 subunit (GluK1Rs; previously known as GluR5 kainate receptors) are concentrated in certain brain regions, where they play a prominent role in the regulation of neuronal excitability, by modulating GABAergic and/or glutamatergic synaptic transmission. In the basolateral nucleus of the amygdala (BLA), which plays a central role in anxiety as well as in seizure generation, GluK1Rs modulate GABAergic inhibition via postsynaptic and presynaptic mechanisms. However, the role of these receptors in the regulation of glutamate release, and the net effect of their activation on the excitability of the BLA network are not well understood. ⋯ Similar intra-BLA injections of UBP302 (20 nmol) had anxiolytic effects in the open field and the acoustic startle response tests, without affecting pre-pulse inhibition. These results suggest that although GluK1Rs in the rat BLA facilitate both GABA and glutamate release, the facilitation of glutamate release prevails, and these receptors can have an anxiogenic and seizurogenic net function. Presynaptic facilitation of glutamate release may, in part, underlie the hyperexcitability-promoting effects of GluK1R activation in the rat BLA.
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To reveal the fundamental processes underlying the different stages of visual object perception, most studies have manipulated relatively complex images, such as photographs, line drawings of natural objects, or perceptual illusions. Here, rather than starting from complex images and working backward to infer simpler processes, we investigated how the visual system parses and integrates information contained in stimuli of the most basic variety. Simple scatterings of a few points of light were manipulated in terms of their numerosity, spatial extent, and organization, and high-density electrophysiological recordings were made from healthy adults engaged in an unrelated task. ⋯ We were guided in our predictions by the "frame-and-fill" model for object perception, whereby fast inputs to the dorsal stream of the visual "where" system first frame the spatial extent of visual objects, which are subsequently "filled-in" by the slower activation of the ventral stream of the visual "what" system. Our findings were consistent with this view, showing a rapidly-onsetting effect of spatial extent in dorsal stream sources, and later-onsetting effects due to dot number and symmetry, which were deemed to be more closely tied to the details of object identity, from ventral stream sources. This collection of observations provides an important baseline from which to understand the spatio-temporal properties of basic visual object perception, and from which to test dysfunction of this system in clinical populations.
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Thiamine deficiency during embryonic or early postnatal development causes deficits in cerebellum-dependent activities including motor control and procedural memory. Here, we give a detailed description of the changes to A-type current in cultured cerebellar granule neurons exposed to thiamine deficiency in vitro. A-type current in treated neurons was reduced to 51% of that in controls. ⋯ These effects were selective because the delayed-rectifier potassium current density and kinetics were unchanged in thiamine-deficient neurons. A computational model of the cerebellar granule neuron was used to test the impact of these alterations and predicts an increase in excitability that is especially pronounced for synaptic activation. Our results suggest that the loss of A-type potassium conductance leads to hyperactivity in cerebellar granule neurons and may contribute to cell death observed in the granule layer of cerebellum during thiamine-deficiency in vivo.
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Accumulating evidence supports the hypothesis of ecstasy and amphetamine exhibiting neurotoxic properties in human recreational users. The extent and exact location of neuronal degeneration might also be associated with a specific profile of cognitive deterioration described in polydrug users. Voxel-based morphometry and cortical thickness analyses constantly gain attention for answering the question of associated neurological sequelae. ⋯ Our data support the hypothesis that massive recreational amphetamine-type stimulant polydrug use is associated with a thinning of cortical grey matter. Disrupted neuronal integrity in frontal regions does fit well into models of addiction and the cognitive deterioration in amphetamine-type stimulant polydrug users. The exact neurotoxic mechanisms of polydrug ecstasy and amphetamine use, however, remain speculative.