Neuroscience
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Pituitary adenylate cyclase-activating polypeptide (PACAP) binds to PACAP-specific (PAC1) receptors in multiple hypothalamic areas, especially those regulating energy balance. PACAP neurons in the ventromedial nucleus (VMN) exert anorexigenic effects within the homeostatic energy balance circuitry. Since PACAP can also reduce the consumption of palatable food, we tested the hypothesis that VMN PACAP neurons project to the ventral tegmental area (VTA) to inhibit A10 dopamine neurons via PAC1 receptors and KATP channels, and thereby suppress binge-like consumption. ⋯ This response was again completely blocked by tolbutamide and PACAP6-38, and associated with a hyperpolarization and decrease in firing. These findings demonstrate that PACAP activates PAC1 receptors and KATP channels to inhibit A10 dopamine neurons and sex-dependently suppress binge-like consumption. Accordingly, they advance our understanding of how PACAP regulates energy homeostasis via the hedonic energy balance circuitry.
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In human, myosin VI (MYO6) haploinsufficiency causes postlingual progressive hearing loss. Because the usefulness of mouse models remains unclear, we produced novel Myo6 null (-/-) mutant mice and analyzed the hearing phenotypes of Myo6+/- (+/-) heterozygous mutants. We first recorded and compared the auditory brainstem responses and distortion product otoacoustic emissions in control Myo6+/+ (+/+) wild-type and +/- mice. ⋯ In particular, the OHCs at the basal area of the cochlea were decreased in +/- mice. IHC ribbon synapses from the area at the base of the cochlea were significantly reduced in +/- mice. Thus, our study indicated that MYO6 haploinsufficiency affected the detection of sounds in mice, and we suggest that +/- mice with Myo6 null alleles are useful animal models for gene therapy and drug treatment in patients with progressive hearing loss due to MYO6 haploinsufficiency.
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We previously observed in rodents that during the 2nd postnatal week corticospinal axons make monosynaptic connections with motoneurons. Prior to that finding, it had been believed that such contacts only occur in higher primates. Although an in vitro electrophysiological study is prerequisite for studying the developmental time course of synaptic connections, the technical difficulty of reliably recording synaptic responses from spinal motoneurons in animals over 2 weeks old hampered the study. ⋯ Thereafter, the monosynaptic connections declined until P21, at which time they were no longer detected. The time course of the falling phase and elimination was confirmed by experiments using optogenetic stimulation. The timing of the elimination fell within the same range (P18-22) estimated in our earlier study using retrograde transsynaptic labeling.
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Distinguishing multiple coding levels in theta band activity during working memory gating processes.
Cognitive control and working memory (WM) processes are essential for goal-directed behaviour. Cognitive control and WM are probably based on overlapping neurophysiological mechanisms. For example, theta-band activity (TBA) plays an important role in both functions. ⋯ The data suggest that the identified processes are implemented in specific neuroanatomical structures. In particular, the medial frontal cortex, temporal cortical regions and insular cortex are involved in these dynamics. The study shows that principles of information coding relevant to cognitive control processes are also crucial for understanding WM gating.
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Glutamate excitotoxicity is one of the important pathophysiological culprits in retinal ganglion cells (RGCs) damage after acute optic nerve injury such as traumatic optic neuropathies and glaucoma. It is necessary to elucidate the mechanism of glutamate injury to RGCs in order to find the relevant neuroprotector. In this study, it was observed that the expression of Parkin increased and peaked at 24 h after glutamate injury to RGCs. ⋯ Moreover, the genetic and pharmacological downregulation of NLRP3 improved survival of RGCs against glutamate excitotoxicity. In the end, knockdown of Parkin exacerbated glutamate induced RGCs damage via triggering NLRP3 inflammasome activation. Taken together, these results shed light on the promising molecular targets for the prevention and treatment of acute optic nerve injury.