Neuroscience
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The subplate is a transient layer between the cortical plate and intermediate zone in the developing cortex. Thalamo-cortical axons form temporary synapses on subplate neurons (SPns) before invading the cortical plate. Neuronal activity within the subplate is of critical importance for the development of neocortical circuits and architecture. ⋯ In the presence of SNAP-5114 CGP55845 did not influence GABAergic transmission, indicating that GABABRs are not activated any longer. We conclude that in the subplate GAT-2/3 operates in reverse mode. GABA released via GAT-2/3 activates presynaptic GABABRs on GABAergic synapses and tonically inhibits GABAergic inputs on SPns.
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Complete spinal transection in adult rats results in poor recovery of hind limb function, whereas significant spontaneous recovery can occur following spinal cord transection in rat neonates. The mechanisms underlying the recovery, however, are poorly understood. Recent studies in rodents suggested that the recovery is not due to axonal regeneration, but rather due to reorganization of the neural circuits in the spinal cord below the injury site, including central pattern generators. ⋯ BDA-positive axons in the rat spinal cord following neonatal spinal transection (neo ST) were longer than those in sham-operated or normal rats. The number of terminal buttons was also higher in spinal cords of neo ST rats compared with sham-operated or normal rats. These findings suggest that sensory fibers project more strongly and make more synapses following neo ST to compensate for the lack of supraspinal projections.
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The potential of non-invasive brain stimulation (NIBS) for studying, and inducing, functionally relevant neuroplasticity is dependent on protocols that can induce lasting, robust and reliable effects. A current limiting factor is the large inter- and intra-subject variability in NIBS-induced neuroplastic responses. There has been some study of inter-subject response variability and factors that contribute to it; however, intra-subject response variability has, so far, received little investigation. ⋯ The most reliable TMS intensity to probe cTBS-induced long-term depression (LTD)-like neuroplastic responses is 150% RMT. This is unlikely to simply be a ceiling effect and, we suggest, may be due to changes in the descending volley evoked at higher stimulus intensities. The perceived stress scale appears to be sufficiently sensitive to measure the influence of subject stress on LTD-like neuroplastic responses.
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Comparative Study
Differential cerebellar GABAA receptor expression in mice with mutations in CaV2.1 (P/Q-type) calcium channels.
Ataxia is the predominant clinical manifestation of cerebellar dysfunction. Mutations in the human CACNA1A gene, encoding the pore-forming α1 subunit of CaV2.1 (P/Q-type) calcium channels, underlie several neurological disorders, including Episodic Ataxia type 2 and Familial Hemiplegic Migraine type 1 (FHM1). Several mouse mutants exist that harbor mutations in the orthologous Cacna1a gene. ⋯ We did not identify differences in the expression of GABAA receptor subunits or in the number of functional GABAA receptors in the non-ataxic R192Q KI strain. In contrast, tg(rol) mice had a ∼15% decrease in the number of functional GABAA receptors, whereas S218L KI mice showed a ∼29% increase. Our data suggest that differential changes in cerebellar GABAA receptor expression profile may contribute to the neurological phenotype of cerebellar ataxia and that targeting GABAA receptors might represent a feasible complementary strategy to treat cerebellar ataxia.
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Acetylcholine (ACh) acts through nicotinic and muscarinic ACh receptors in the ventral midbrain and striatal areas to influence dopamine (DA) transmission. This cholinergic control of DA transmission is important for processes such as attention and motivated behavior, and is manipulated by nicotine in tobacco products. Identifying and characterizing the key ACh receptors involved in cholinergic control of DA transmission could lead to small molecule therapeutics for treating disorders involving attention, addiction, Parkinson's disease, and schizophrenia. α6-Containing nicotinic acetylcholine receptors (nAChRs) are highly and specifically expressed in midbrain DA neurons, making them an attractive drug target. ⋯ To complement these behavioral studies, we studied the ability of in vivo α6(∗) nAChR activation to support plasticity changes in midbrain DA neurons that are relevant to behavioral sensitization and addiction. By coupling local infusion of drugs and brain slice patch-clamp electrophysiology, we show that activating α6(∗) nAChRs in midbrain DA areas is sufficient to enhance glutamatergic transmission in ventral tegmental area (VTA) DA neurons. Together, these results from in vivo studies strongly suggest that α6(∗) nAChRs expressed by VTA DA neurons are positioned to strongly influence both DA-mediated behaviors and the induction of synaptic plasticity by nicotine.