Neuroscience
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Cerebral ischemia causes blood flow derangements characterized by hyperemia (increased cerebral blood flow, CBF) and subsequent hypoperfusion (decreased CBF). We previously demonstrated that protein kinase C delta (δPKC) plays an important role in hippocampal neuronal death after ischemia. However, whether part of this protection is due to the role of δPKC on CBF following cerebral ischemia remains poorly understood. ⋯ Sprague-Dawley (SD) rats pretreated with a δPKC specific inhibitor (δV1-1, 0.5 mg/kg) exhibited attenuation of hyperemia and latent hypoperfusion characterized by vasoconstriction followed by vasodilation of microvessels after 2-vessel occlusion plus hypotension measured by 2-photon microscopy. In an asphyxial cardiac arrest model (ACA), SD rats treated with δV1-1 (pre- and post-ischemia) exhibited improved perfusion after 24 h and less hippocampal CA1 neuronal death 7 days after ACA. These results suggest possible therapeutic potential of δPKC in modulating CBF and neuronal damage after cerebral ischemia.
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Spinal nerves and their associated dorsal root ganglion (DRG) cells can be subject to mechanical deformation and hypoxia associated with pathology such as disc herniation, spinal stenosis and spine trauma. There is very limited information on the response of adult DRG neurons to such stressors. In this study we used an in vitro approach to examine the response of adult DRG cells to (a) mechanical, hypoxic, and combined injuries; and (b) to compare the effects on injury on nociceptive and non-nociceptive neurons, as well as on non-neuronal cells. ⋯ Total cell death in response to mechanical injury or hypoxia was similar in both non-nociceptive (neurofilament, NF-200 immunoreactive) and nociceptive (calcitonin gene-related peptide, CGRP immunoreactive) neurons, but apoptosis (assessed by activated caspase-3 immunostaining) was significantly higher in CGRP than NF-200 neurons. Surprisingly, cell death of non-peptidergic nociceptors (identified by Griffonia simplicifolia IB4 lectin binding) was already high in control cultures, and was not increased further by either mechanical stretch or hypoxia. These results provide detailed information on the response of adult DRG subpopulations to hypoxia and mechanical strain, and describe in vitro models that could be useful for screening potential neuroprotective agents.
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Impairments in executive function and cognitive control are a common feature of neuropsychiatric and neurodegenerative disorders. A promising behavioral paradigm for elucidating the neural mechanisms of executive function is extradimensional/intradimensional (ED/ID) shifting, which places demands on executive function by requiring the adjustment of behavioral responses based on affective or attentional information. ⋯ However, increased Fos-LI was also present in rats that performed a yoked number of additional control discrimination trials, without affective or attentional shifting. These observations suggest that cortical networks required for affective and attentional shifting are also activated during comparable discrimination tasks that do not require shifting, consistent with a role for these networks in monitoring ongoing behavior even in situations in which adaptation to changing behavioral demands is not required.
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Intersegmental interneurons with relatively short axons perform an important role in the coordination of limb movement but surprisingly little is known about their organization and how they contribute to neuronal networks in the adult rat. We undertook a series of anatomical tract-tracing studies to label cell bodies and axons of intersegmental neurons in the lumbar cord and characterized their neurochemical properties by using immunocytochemistry. The b-subunit of cholera toxin was injected into L1 or L3 segments of seven rats in the vicinity of lateral or medial motor nuclei. ⋯ In contrast, 19% of all intra-segmental axons in the L3 contralateral lateral motor nucleus were found to be purely glycinergic and 17% contained a mixture of GABA and glycine. This study shows that short range interneurons form extensive ipsi- and contralateral projections within the lumbar enlargement and that many of them contain calcium binding proteins. Those projecting contralaterally to motor nuclei are predominantly excitatory.
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The hippocampus plays a central role in memory formation in the mammalian brain. The subiculum is the principal target of CA1 pyramidal cells and thus serves as the major relay station for the outgoing hippocampal information. Pyramidal cells in the subiculum have been classified as burst-spiking (BS) and regular-spiking (RS) cells. ⋯ The isoproterenol-induced LTP in (BS) cells does not depend on postsynaptic Ca(2+)-signaling, as 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) does not prevent its induction. Furthermore, paired-pulse facilitation (PPF) and coefficient of variation (CV) analysis indicate the site of the LTP expression to be presynaptic. Our findings show that activation of β-adrenergic receptors (β-ARs) at CA1-subiculum synapses induces a cell-type-specific form of chemical LTP in subicular (BS) cells that may allow a target-specific trafficking of hippocampal output.