Neuroscience
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The mature neocortex is a unique six-layered mammalian brain region. It is composed of morphologically and functionally distinct subpopulations of primary projection neurons that form complex circuits across the central nervous system. The precisely-timed generation of projection neurons from neural stem cells governs their differentiation, postmitotic specification, and signaling, and is critical for cognitive and sensorimotor ability. ⋯ Indeed, mRNA transcripts undergo many post-transcriptional regulatory steps before the production of functional proteins, which specify neocortical neural stem cells and subpopulations of neocortical neurons. Therefore, particular attention is paid to the differential post-transcriptional regulation of key transcripts by RNA-binding proteins, including splicing, localization, stability, and translation. We also present a transcriptome screen of candidate molecules associated with post-transcriptional mRNA processing that are differentially expressed at key developmental time points across neocortical prenatal neurogenesis.
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The hippocampus, derived from medial regions of the telencephalon, constitutes a remarkable brain structure. It is part of the limbic system, and it plays important roles in information encoding, related to short-term and long-term memory, and spatial navigation. It has also attracted the attention of many clinicians and neuroscientists for its involvement in a wide spectrum of pathological conditions, including epilepsy, intellectual disability, Alzheimer disease and others. ⋯ As well as original landmark findings, modern techniques such as large-scale in situ hybridizations, in utero electroporation and the study of mouse mutants with hippocampal phenotypes, add further detail to our knowledge of the finely regulated processes which form this intricate structure. Molecular signatures are being revealed related to field, intra-field and laminar cell identity, as well as, cell compartments expressing surface proteins instrumental for connectivity. We summarize here old and new findings, and highlight elegant tools used to fine-study hippocampal development.
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Children with autism spectrum disorder (ASD) and age-matched typically-developing (TD) peers were tested on two forms of eyeblink conditioning (EBC), a Pavlovian associative learning paradigm where subjects learn to execute an appropriately-timed eyeblink in response to a previously neutral conditioning stimulus (CS). One version of the task, trace EBC, interposes a stimulus-free interval between the presentation of the CS and the unconditioned stimulus (US), a puff of air to the eye which causes the subjects to blink. In delay EBC, the CS overlaps in time with the delivery of the US, usually with both stimuli terminating simultaneously. ⋯ However, when subsequently tested on delay EBC, subjects with ASD displayed abnormally-timed conditioned eye blinks that began earlier and peaked sooner than those of TD subjects, consistent with previous findings. The results suggest an impaired ability of children with ASD to properly time conditioned eye blinks which appears to be specific to delay EBC. We suggest that this deficit may reflect a dysfunction of the cerebellar cortex in which increases in the intensity or duration of sensory input can temporarily disrupt the accuracy of motor timing over short temporal intervals.
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Estrogen receptors (ERs) α and β are involved in the regulation of the nitrergic system in the supraoptic (SON) and paraventricular (PVN) nuclei under basal conditions. In this study we have assessed whether ERs are also involved in the modulation of the nitrergic system in the SON and PVN under acute systemic hypertonic conditions. Adult ovariectomized rats received a single injection of either estradiol, a selective ERα agonist, a selective ERβ agonist, a selective ERα antagonist, a selective ERβ antagonist or vehicle. ⋯ In contrast, the inhibition of ERα enhanced the effect of NaCl, inducing a further decrease in the number of NADPH-diaphorase-positive cells. Moreover, the ERβ agonist enhanced and the ERβ antagonist blocked the effect of NaCl on the number of NADPH-diaphorase-positive neurons in the SON and in the medial magnocellular subdivision of the PVN. These findings indicate that estradiol regulates the nitrergic system in the SON and PVN under acute osmotic stress conditions, but the effects specifically depend on the anatomical subregions and different ERs.
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Nerve growth factor (NGF) is an important mediator in the initiation of the inflammatory response and NGF via activation of the p75 neurotrophin receptor (p75(NTR)) and downstream sphingomyelin signaling leads to significant enhancement of the excitability of small-diameter sensory neurons. Because of the interaction between sphingomyelin and cholesterol in creating membrane liquid-ordered domains known as membrane or lipid rafts, we examined whether neuronal NGF-induced sensitization via p75(NTR) was dependent on the integrity of membrane rafts. Here, we demonstrate that the capacity of NGF to enhance the excitability of sensory neurons may result from the interaction of p75(NTR) with its downstream signaling partner(s) in membrane rafts. ⋯ In addition, adding back MβCD with cholesterol restored the NGF-induced sensitization in previously cholesterol-depleted neurons, suggesting that cholesterol and the structural integrity of rafts are key to promoting NGF-mediated sensitization. Using established protocols to isolate detergent-resistant membranes, both p75(NTR) and the neuronal membrane raft marker, flotillin, localize to raft fractions. These results suggest that downstream signaling partners interacting with p75(NTR) in sensory neurons are associated with membrane raft signaling platforms.