The Journal of neuroscience : the official journal of the Society for Neuroscience
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The subventricular zone (SVZ) of the postnatal brain continuously generates olfactory bulb (OB) interneurons. We show that calretinin+, calbindin+, and dopaminergic (TH+) periglomerular OB interneurons correspond to distinct subtypes of GABAergic cells; all were produced in the postnatal mouse brain, but they matured and were eliminated at different rates. The embryonic lateral ganglionic eminence (LGE) is thought to be the site of origin of postnatal SVZ neural progenitors. ⋯ Emx1 lineage-derived cells contributed a substantial portion of GABAergic cells in the OB, including calretinin+ interneurons. This is in contrast to cortex, in which Emx1 lineage-derived cells do not differentiate into GABAergic neurons. Our results suggest that some OB interneurons are derived from progenitors outside the LGE and that precursors expressing what has classically been considered a pallial transcription factor generate GABAergic interneurons.
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A single administration of cocaine or D-amphetamine produces acute hyperlocomotion and long-lasting increased sensitivity to subsequent injections. This locomotor sensitization reveals the powerful ability of psychostimulants to induce brain plasticity and may participate in the alterations that underlie addiction. We investigated the role of cannabinoid receptor type 1 (CB1-R) in the effects of a single injection of psychostimulants. ⋯ In contrast, cocaine-induced phosphorylation of extracellular signal-regulated kinase (ERK) was blocked in both CB1-R mutant and antagonist-pretreated mice. Conditional deletion of CB1-R in forebrain principal neurons or GABAergic neurons prevented cocaine-induced ERK activation in dorsal striatum and nucleus accumbens. Our results provide strong evidence for the role of the endocannabinoid system in regulating neuronal circuits critical for long-lasting effects of cocaine, presumably by acting on CB1-R located on terminals of striatal medium spiny neurons.
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Randomized Controlled Trial Comparative Study
Activation of prefrontal cortex by transcranial direct current stimulation reduces appetite for risk during ambiguous decision making.
As adult humans, we are continuously faced with decisions in which proper weighing of the risk involved is critical. Excessively risky or overly cautious decision making can both have disastrous real-world consequences. Weighing of risks and benefits toward decision making involves a complex neural network that includes the dorsolateral prefrontal cortex (DLPFC), but its role remains unclear. ⋯ Anodal tDCS over DLPFC by itself did not significantly change risk-taking behaviors; however, when the contralateral DLPFC was modulated with cathodal tCDS, an important decrease in risk taking was observed. Also, the induced cautious decision-making behavior was observed only when activity of both DLPFCs was modulated. The ability to modify risk-taking behavior may be translated into therapeutic interventions for disorders such as drug abuse, overeating, or pathological gambling.
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Activity-dependent changes in neurons of the rat superficial dorsal horn are crucial for the induction and maintenance of neuropathic and inflammatory pain states. To identify the molecular mechanisms underlying this sensitization of superficial dorsal horn neurons, we undertook a genome-wide microarray profiling of dorsal horn gene transcripts at various times after induction of peripheral inflammation of the rat ankle joint. At early time points, upregulation of gene expression dominated, but by 7 d, downregulation was predominant. ⋯ SGK1 protein was also localized, in part, to lamina I projection neurons, and its expression in the superficial dorsal horn increased after inflammation. Furthermore, antisense knock-down of SGK1 delayed the onset of inflammatory hyperalgesia by 24 h at least. Our results uncover an unexpected complexity in the regulation of gene expression, including the modulation of transcriptional repression, that accompanies development and maintenance of an inflammatory pain state.