Neuroscience
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Patients with post-traumatic stress disorder (PTSD) present hippocampal (HPC) dysfunction, which may facilitate fear-related phenomena such as fear learning sensitization (i.e. potentiation of fear acquisition by initial fear conditioning (FC1)) and fear return (i.e. reactivation of extinguished fear). Fear return is sensitive to HPC high-frequency stimulation (HFS) in rats. The goal of the present study was to examine whether fear learning sensitization is also sensitive to HPC HFS in rats. ⋯ We also found that the effect of HPC HFS on fear learning sensitization required initial extinction. These findings suggest a pivotal role of the HPC in preventing proactive and retroactive effects of successive fear conditionings. These data also support the concept that HPC deactivation may be involved in fear learning sensitization and fear return in PTSD patients.
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The visceral insular cortex (VIC) has previously been shown to play a critical role during acute nausea-induced conditioned gaping in rats. Specifically, localized administration of the conventional anti-emetic, ondansetron or the synthetic cannabinoid, HU210, interferes with the establishment of conditioned gaping, likely by reducing the effects of an illness-inducing treatment. However the precise role of the VIC in endocannabinoid-suppression of nausea remains unknown; thus we investigated the potential of localized intra-VIC endocannabinoid administration to interfere with acute nausea-induced conditioned gaping behavior in male Sprague-Dawley rats. ⋯ Bilateral intra-VIC infusions of 2-AG (1 μg, but not 0.5 μg) dose-dependently suppressed conditioned gaping, whereas exogenous AEA was without effect. Interestingly, 2-AG reduced conditioned gaping despite additional pretreatment with the selective cannabinoid receptor type 1 (CB1) antagonist, AM-251; however, concomitant pretreatment with the cyclooxygenase inhibitor, indomethacin (0.5 μg), blocked the suppressive effects of intra-VIC 2-AG. These findings suggest that the modulatory role of the endocannabinoid system during nausea is driven largely by the endocannabinoid, 2-AG, and that its anti-nausea effects may be partly independent of CB1-receptor signaling through metabolic products of the endocannabinoid system.
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Mice do not require the brain in order to maintain constricted pupils. However, little is known about this intrinsic pupillary light reflex (iPLR) beyond a requirement for melanopsin in the iris and an intact retinal ciliary marginal zone (CMZ). Here, we study the mouse iPLR in vitro and examine a potential role for outer retina (rods and cones) in this response. ⋯ We also identify an important role for pigmentation in the development of the mouse iPLR, with only a weak and transient response present in albino animals. Our results show that the iPLR in mice develops unexpectedly late and are consistent with a role for rods and pigmentation in the development of this response in mice. The enhancement of the iPLR in aged degenerate mice was extremely surprising but may have relevance to behavioral observations in mice and patients with retinitis pigmentosa.
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Reports suggest that silent information regulation 2 homolog 3 (SIRT3) protects cardiomyocytes from oxidative stress-mediated death. SIRT3, a mitochondrial protein, is an essential regulator of mitochondrial function, and this regulation is important in many cerebrovascular diseases, especially stroke. Here, we investigated the role of SIRT3 in ischemia-induced neuronal death due to oxygen-glucose deprivation (OGD) using an in vitro model of cerebral ischemia. ⋯ Both SIRT3 and PGC-1α knockdown led to reduced mitochondrial membrane potential (Δψ) and Ca(2+) transients, especially under OGD conditions. Thus, our data suggest that SIRT3 protects PC12 cells from hypoxic injury via a mechanism that may involve PGC-1α and MnSOD. SIRT3 and PGC-1α regulate each other under physiologic and OGD conditions, thereby partially protecting against hypoxia or ischemia.
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Norepinephrine acting via β-adrenergic receptors (β-ARs) plays an important role in hippocampal plasticity including the subiculum which is the principal target of CA1 pyramidal cells and which controls information transfer from the hippocampus to other brain regions including the neighboring presubiculum and the entorhinal cortex (EC). Subicular pyramidal cells are classified as regular- (RS) and burst-spiking (BS) cells. Activation of β-ARs at CA1-subiculum synapses induces long-term potentiation (LTP) in burst- but not in RS cells (Wójtowicz et al., 2010). ⋯ In pilocarpine-treated animals, β-AR-mediated LTP was strongly reduced in the distal subiculum. The attenuated LTP was associated with a disturbed polysynaptic transmission from the CA1, via the subiculum to the presubiculum, but with a preserved transmission to the medial EC. Our findings suggest that synaptic plasticity may influence target-related information flow and that such regulation is disturbed in pilocarpine-treated epileptic rats.