Neuroscience
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The present study was designed to investigate possible involvement of the central amygdala (CeA) nicotinic acetylcholine (nACh) and 5-hydroxytryptamine 1A (5-HT1A) receptors in the reversal effect of nicotine and 3,4-methylenedioxy-N-methylamphetamine (MDMA or ecstasy) on morphine-induced amnesia. Two guide cannulas were stereotaxically implanted in the CeA regions and a step-through passive avoidance task was used for the assessment of memory retrieval in adult male Wistar rats. Our results indicated that post-training s.c. administration of morphine (3-7-mg/kg) impaired memory retrieval. ⋯ Moreover, pre-test injection of the same doses of mecamylamine or (S)-WAY 100135 into the CeA alone could not change memory retrieval. Taken together, it can be concluded that there is a functional interaction between morphine, nicotine and MDMA via the CeA nicotinic and serotonergic receptor mechanisms in passive avoidance memory retrieval. Moreover, cross state-dependent memory retrieval may have been induced between the drugs and this probably depends on the rewarding effects of the drugs.
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Homeostatic plasticity is engaged when neurons need to stabilize their synaptic strength and excitability in response to acute or prolonged destabilizing changes in global activity. Compared to the extensive studies investigating the molecular mechanisms for homeostatic synaptic plasticity, the mechanism underlying homeostatic intrinsic plasticity is largely unknown. Through whole-cell patch-clamp recording in low-density cultures of dissociated hippocampal neurons, we demonstrate here that prolonged activity blockade induced by the sodium channel blocker tetrodotoxin (TTX) leads to increased action potential firing rates. ⋯ Prolonged activity enhancement also enhanced potassium (K(+)) current through Kv1 channels, suggesting that changes in K(+) current, in part, mediate stabilization of hippocampal neuronal excitability upon prolonged activity elevation. In contrast to the previous reports showing that L-type voltage-gated calcium (Ca(2+)) channels solely mediate homeostatic regulation of excitatory synaptic strength (Ibata et al., 2008; Goold and Nicoll, 2010), inhibition of N-Methyl-d-aspartate (NMDA) receptors alone mimics the elevation in firing frequency driven by prolonged TTX application, while the decrease in firing rates induced by prolonged BC treatment involves the activity of NMDA receptors and L-type voltage-gated Ca(2+) channels. These results collectively provide strong evidence that alterations in Ca(2+) influx through NMDA receptors and L-type voltage-gated Ca(2+) channels mediate homeostatic intrinsic plasticity in hippocampal neurons in response to prolonged activity changes.
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MicroRNAs (miRNAs) have emerged as a major regulator in neurological diseases, and understanding their molecular mechanism in modulating cerebral ischemic injury may provide potential therapeutic targets for ischemic stroke. However, as one of 19 differentially expressed miRNAs in mouse brain with middle cerebral artery occlusion (MCAO), the role of miR-134 in ischemic injury is not well understood. In this study, the miR-134 expression level was manipulated both in oxygen-glucose deprivation (OGD)-treated N2A neuroblastoma cells in vitro and mouse brain with MCAO-induced ischemic stroke in vivo, and its possible targets of heat shock protein A5 (HSPA5) and HSPA12B were determined by bioinformatics analysis and dual luciferase assay. ⋯ It could attenuate brain infarction size and neural cell damage, and improve neurological outcomes in mice with ischemic stroke, whereas upregulation of miR-134 had the opposite effect. In addition, HSPA12B was validated to be a target of miR-134 and its short interfering RNAs (siRNAs) could block miR-134 inhibitor-induced neuroprotection in OGD-treated N2A cells. In conclusion, downregulation of miR-134 could induce neuroprotection against ischemic injury in vitro and in vivo by negatively upregulating HSPA12B protein expression.
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The neural pathways of the auditory system underlie our ability to detect sounds and to transform amplitude and frequency information into rich and meaningful perception. While it shares some organizational features with other sensory systems, the auditory system has some unique functions that impose special demands on precision in circuit assembly. In particular, the cochlear epithelium creates a frequency map rather than a space map, and specialized pathways extract information on interaural time and intensity differences to permit sound source localization. ⋯ These proteins provide graded cues used in establishing tonotopically ordered connections between auditory areas, as well as discrete cues that enable axons to form connections with appropriate postsynaptic partners within a target area. Throughout the auditory system, Eph proteins help to establish patterning in neural pathways during early development. This early targeting, which is further refined with neuronal activity, establishes the precision needed for auditory perception.
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Birdsong offers a unique model system to understand how a developing brain - once given a set of purely acoustic targets - teaches itself the vocal-tract gestures necessary to imitate those sounds. Like human infants, to juvenile male zebra finches (Taeniopygia guttata) falls the burden of initiating the vocal-motor learning of adult sounds. ⋯ Distinct forebrain pathways for structured (theme) and unstructured (variation) singing not only raise new questions about mechanisms of sensory-motor integration, but also provide a fascinating new research opportunity. A cortical locus for a motor memory of the learned song is now firmly established, meaning that anatomical, physiological, and computational approaches are poised to reveal the neural mechanisms used by the brain to compose the songs of birds.