Neuroscience
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The notion of functional interactions between the alpha7 nicotinic acetylcholine (alpha7 nACh) and the cannabinoid systems is emerging from recent in vitro and in vivo studies. Both the alpha7 nACh receptor and the cannabinoid receptor 1 (CB1) are highly expressed in the hippocampus. To begin addressing possible anatomical interactions between the alpha7 nACh and the cannabinoid systems in the rat hippocampus, we investigated the distribution of neurons expressing alpha7 nACh mRNA in relation to those containing CB1 mRNA. ⋯ We found that these alpha7 nACh/CB1 interneurons are the major subpopulation of hippocampal interneurons expressing CB1 mRNA. The alpha7 nACh expressing interneurons represent half of the detected population of CCK containing neurons in the hippocampus. Since it is well established that the vast majority of hippocampal interneurons expressing CB1 mRNA have 5-HT type 3 (5-HT3) receptors, we conclude that these hippocampal alpha7 nACh/5HT3/CB1/CCK interneurons correspond to those previously postulated to relay inputs from diverse cortical and subcortical regions about emotional, motivational, and physiological states.
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Pontine noradrenergic neurons of the locus coeruleus (LC) and sub-coeruleus (SubC) region cease firing during rapid eye movement sleep (REMS). This plays a permissive role in the generation of REMS and may contribute to state-dependent modulation of transmission in the CNS. Whether all pontomedullary catecholaminergic neurons, including those in the A1/C1, A2/C2 and A7 groups, have REMS-related suppression of activity has not been tested. ⋯ In contrast, neither of these correlations was significant for A1 /C1 or caudal A5 neurons. These findings suggest that, similar to the prototypic LC neurons, neurons of the A7, rostral A5 and A2/C2 groups have reduced or abolished activity during REMS, whereas A1 /IC1 and caudal A5 neurons do not have this feature. The reduced activity of A2/C2, A5 and A7 neurons during REMS, and the associated decrements in norepinephrine release, may cause state-dependent modulation of.transmission in brain somato- and viscerosensory, somatomotor, and cardiorespiratory pathways.
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The anesthetic gas nitrous oxide (N2O) and the volatile anesthetic isoflurane (ISO) are commonly used in surgical procedures for human infants and in veterinary and laboratory animal practice to produce loss of consciousness and analgesia. Recent reports indicate that exposure of the developing brain to general anesthetics that block N-methyl-D-aspartate (NMDA) glutamate receptors or potentiate GABA(A) receptors can trigger widespread apoptotic neurodegeneration. In the present study, the question arises whether a relatively low dose of ISO alone or its combination with N2O entails significant risk of inducing enhanced apoptosis. ⋯ However, enhanced apoptotic cell death was apparent when N2O was combined with ISO at exposure durations of 6 h or more. Co-administration of L-carnitine (300 or 500 mg/kg, i.p.) effectively protected neurons from the anesthetic-induced damage. These data indicate that 6 h or more of inhaled anesthetic exposure consisting of a combination of N2O and ISO results in enhanced neuronal apoptosis, and L-carnitine effectively blocks the neuronal apoptosis caused by inhalation anesthetics in the developing rat brain.
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Members of the regulator of G protein signaling 7 (RGS7) (R7) family and Gbeta5 form obligate heterodimers that are expressed predominantly in the nervous system. R7-Gbeta5 heterodimers are GTPase-activating proteins (GAPs) specific for Gi/o-class Galpha subunits, which mediate phototransduction in retina and the action of many modulatory G protein-coupled receptors (GPCRs) in brain. ⋯ Furthermore, R7BP and R7 protein accumulation in vivo requires Gbeta5. 2) Expression of R7BP in Neuro2A cells at levels approximating those in brain recruits endogenous RGS7-Gbeta5 complexes to the plasma membrane. 3) R7BP immunoreactivity in brain concentrates in neuronal soma, dendrites, spines or unmyelinated axons, and is absent or low in glia, myelinated axons, or axon terminals. 4) RGS7-Gbeta5-R7BP complexes in brain extracts associate inefficiently with detergent-resistant lipid raft fractions with or without G protein activation. 5) R7BP and Gbeta5 protein levels are upregulated strikingly during the first 2-3 weeks of postnatal brain development. Accordingly, we suggest that R7-Gbeta5-R7BP complexes in the mouse or rat could regulate signaling by modulatory Gi/o-coupled GPCRs in the developing and adult nervous systems.
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Cannabinoids have long been associated with mnemonic deficits. However, existing evidence has generally focused on the effect of cannabinoids when they are delivered prior to task-training, and such findings are confounded by possible drug effects on sensory, motor, and/or motivational systems that support the acquisition and the expression of learning. The present study investigated the effects of the CB1-receptor agonist WIN 55,212-2 (WIN) on memory consolidation in the Morris water maze. ⋯ Rats bilaterally infused with WIN at 2.5 microg and 5 microg (per side) during training spent significantly less time in the target quadrant than vehicle controls on probe trial 4 weeks later, while no difference was seen at 1-week retention. Taken together, our results showed that post-training activation of CB1 receptors in the hippocampus disrupts long-term memory consolidation but has no effect on acquisition and short-term retention. Plausible pharmacological interactions between cannabinoids and other neurotransmitter systems and associated plasticity mechanisms are discussed.