Neuroscience
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Activity-regulated, cytoskeletal-associated protein (Arc) is an immediate early gene induced in excitatory circuits following behavioral episodes. Arc mRNA is targeted to activated regions of the dendrite after long-term potentiation (LTP) of the dentate gyrus, a process dependent on NMDA receptor activation. We used post-embedding immunogold electron microscopy (EM) to test whether synaptic Arc expression patterns are selectively modified by plasticity. ⋯ Post-embedding EM revealed Arc immunogold labeling in three times as many spines in the middle molecular layer of the stimulated dentate gyrus than in either the ipsilateral outer molecular layer or the contralateral middle and outer molecular layers. This upregulation did not occur with low frequency stimulation of the perforant path. Therefore Arc protein localization may be a powerful tool to isolate recently activated dendritic spines.
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A selective GABA(B) receptor agonist, baclofen, is known to suppress neuropathic pain. In the present study, we investigated the effect of baclofen on the excitability of trigeminal root ganglion (TRG) neurons by using the whole cell and perforated patch-clamp recording techniques. Under voltage-clamp (V(h)=-60 mV), voltage-dependent K(+) currents were recorded in the small diameter TRG neurons (<30 microm) and isolated by blocking Na(+) and Ca(2+) currents with appropriate ion replacement. ⋯ Application of baclofen reduced action potential duration evoked by a depolarization current pulse. These results indicated that activation of GABA(B) receptors inhibits the excitability of rat small diameter TRG neurons and this inhibitory action is mediated by potentiation of voltage-dependent K(+) currents. We therefore concluded that modification of nociceptive transmission in the trigeminal system by activation of GABA(B) receptors occurs at the level of small TRG neuron cell bodies and/or their primary afferent terminals, which are potential targets of analgesia by baclofen.
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Glycinergic membrane responses have been described in cortical plate neurons (CPn) and Cajal-Retzius cells (CRc) during early neocortical development. In order to elucidate the functional properties and molecular identity of glycine receptors in these two neuronal cell types, we performed whole-cell patch-clamp recordings and subsequent single-cell multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) analyses on visually identified neurons in tangential and coronal slices as well as in situ hybridizations of coronal slices from neonatal rat cerebral cortex (postnatal days 0-4). In both CPn and CRc the glycinergic agonists glycine, beta-alanine and taurine induced inward currents with larger current densities in CRc. ⋯ In situ hybridization histochemistry showed the expression of mRNAs for alpha(2) and beta subunits within the cortical plate and in large neurons of the marginal zone, while there were no signals for alpha(1) and alpha(3) subunits. In summary, these results suggest that CPn and CRc express glycine receptors with similar functional and pharmacological properties. The correlation of pharmacological properties and mRNA expression suggests that the glycine receptors in both cell types may consist of alpha(2)/beta heteromeric receptors.
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Comparative Study
Individual responses to novelty predict qualitative differences in d-amphetamine-induced open field but not reward-related behaviors in rats.
Differences in the locomotor response of rats to a novel environment (high responders [HR] versus low responders [LR]) have been associated with differences in vulnerability to psychostimulants. In the present study we profiled extensively the behavioral repertoire of HR and LR rats (differentiated on the basis of vertical activity) during exposure to a novel environment and in response to d-amphetamine (d-amp; 1.5 mg/kg, i.p.). Moreover, we ascertained whether HR and LR rats differ in the rewarding effects of medial forebrain bundle electrical self-stimulation and in the ability of d-amp to increase the reinforcing efficacy of self-stimulation. ⋯ Additionally, brain stimulation reward thresholds for the two groups were not differentially affected by d-amp. The above results suggest that HR and LR can be further differentiated upon exposure to a novel environment and in response to d-amp. This differentiation is primarily based on qualitative cohorts of their behavioral structure, but not on deviations in the reward processes as assessed by intracranial self-stimulation.
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Comparative Study
Accumulation of Ym1/2 protein in the mouse olfactory epithelium during regeneration and aging.
A unique feature of the olfactory system is its efficiency to produce new neurons in the adult. Thus, destruction of the olfactory receptor neurons (ORNs) using chemical (intranasal perfusion with ZnSO4) or surgical (axotomy or bulbectomy) methods, leads to an enhanced rate of proliferation of their progenitors and to complete ORNs regeneration. The aim of our study was to identify new factors implied in this regenerative process. ⋯ In the olfactory mucosa of control mice, Ym1/2 was hardly detectable in young animals and became more and more abundant with increasing age. In injured and aged mice, Ym1/2 mainly accumulates in the cytoplasm of supporting cells as well as in other cells located throughout the olfactory epithelium. Our results suggest that Ym1/2 is involved in olfactory epithelium remodeling following several kinds of lesions of the adult olfactory mucosa and support the view of a critical role of inflammatory cues in neurodegeneration and aging.