Neuroscience
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Activity-dependent and sustained alterations in synaptic efficacy are widely regarded as the cellular correlates underlying learning and memory. Metabotropic glutamate receptors (mGluRs) are intrinsically involved in both hippocampal synaptic plasticity and spatial learning. Group II mGluRs are required for persistent hippocampal long-term depression (LTD), but are not required for long-term potentiation (LTP) in the hippocampal CA1 region in vivo. ⋯ Following six daily applications of EGLU a clear impairment of LTD but not LTP was apparent however. These data support that prolonged antagonism of group II mGluRs results in an impairment of LTD that parallels the appearance of spatial memory deficits arising from group II mGluR antagonism. These findings support the importance of group II mGluRs for spatial memory formation and offer a further link between LTD and the encoding of spatial information in the hippocampus.
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AMPA receptors have been identified in different populations of presynaptic terminals and found to be involved in the modulation of neurotransmitter release. The mechanisms that govern the expression of presynaptic AMPA receptors are not known. One possibility is that pre- and postsynaptic AMPA receptors are regulated according to the same principles. ⋯ Subfractionation and high-resolution immunogold analyses of the rat hippocampus revealed that GluR2 and PICK1 are enriched postsynaptically, but also in presynaptic membrane compartments, including the active zone and vesicular membranes. PICK1 and GluR2 are associated with the same vesicles, which are immunopositive also for synaptophysin and vesicle-associated membrane protein 2. Based on what is known about the function of PICK1 postsynaptically, the present data suggest that PICK1 is involved in the regulation of presynaptic AMPA receptor trafficking and in determining the size of the AMPA receptor pool that modulates presynaptic glutamate release.
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Attention-deficit/hyperactivity disorder (ADHD) is the most common neurobehavioural disorder among children. ADHD children are hyperactive, impulsive and have problems with sustained attention. These cardinal features are also present in the best validated animal model of ADHD, the spontaneously hypertensive rat (SHR), which is derived from the Wistar Kyoto rat (WKY). ⋯ This indicates that the SHR has a functional predominance of NR2B, a feature characteristic of early developmental stages in these synapses. Quantitative immunofluorescence and electron microscopic postembedding immunogold cytochemistry of the three major NMDAR subunits (NR1, NR2A; and NR2B) in stratum radiatum spine synapses revealed no differences between SHR and WKY. The results indicate that functional impairments in glutamatergic synaptic transmission may be one of the underlying mechanisms leading to the abnormal behavior in SHR, and possibly in human ADHD.
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Activity regulated cytoskeletal protein (Arc), c-fos and zif268 are immediate early genes (IEGs) important for adult brain plasticity. We examined developmental expression of these IEGs and the effect of neonatal noradrenergic lesion on their expression in developing and mature brain. N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP-4), a specific noradrenergic neurotoxin, was administered to rats on postnatal day (PND) 3 and in situ hybridization was used to assay Arc, c-fos and zif268 mRNA on PND 13, 25 and 60. ⋯ These data indicate that norepinephrine regulation of IEG expression differs in developing and mature brain and that loss of developmental norepinephrine leads to abnormally high postnatal IEG expression. Previous studies have shown an important role for norepinephrine in brain development. Our data support the idea that norepinephrine plays an important role during CNS development and that changes in noradrenergic signaling during development may have long lasting effects, potentially on learning and memory.
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Serotonergic systems in the dorsal raphe nucleus are thought to play an important role in the regulation of anxiety states. To investigate responses of neurons in the dorsal raphe nucleus to a mild anxiety-related stimulus, we exposed rats to an open-field, under low-light or high-light conditions. Treatment effects on c-Fos expression in serotonergic and non-serotonergic cells in the midbrain raphe nuclei were determined 2 h following open-field exposure or home cage control (CO) conditions. ⋯ Dual immunostaining for c-Fos and CTb revealed an increase in the percentage of c-Fos-immunoreactive BL-projecting neurons in open-field-exposed rats compared with handled and control rats. Dual immunostaining for tryptophan hydroxylase and CTb revealed that a majority (65%) of BL-projecting neurons were serotonergic, leaving open the possibility that activated neurons were serotonergic, non-serotonergic, or both. These data are consistent with the hypothesis that exposure to anxiogenic stimuli activates a subset of neurons in the midbrain raphe complex projecting to amygdala anxiety circuits.