Ventromedial Thalamus-Projecting DCN Neurons Modulate Associative Sensorimotor Responses in Mice / 神经科学通报·英文版

The deep cerebellar nuclei (DCN) integrate various inputs to the cerebellum and form the final cerebellar outputs critical for associative sensorimotor learning. However, the functional relevance of distinct neuronal subpopulations within the DCN remains poorly understood. Here, we examined a subpopulation of mouse DCN neurons whose axons specifically project to the ventromedial (Vm) thalamus (DCNVm neurons), and found that these neurons represent a specific subset of DCN units whose activity varies with trace eyeblink conditioning (tEBC), a classical associative sensorimotor learning task. Upon conditioning, the activity of DCNVm neurons signaled the performance of conditioned eyeblink responses (CRs). Optogenetic activation and inhibition of the DCNVm neurons in well-trained mice amplified and diminished the CRs, respectively. Chemogenetic manipulation of the DCNVm neurons had no effects on non-associative motor coordination. Furthermore, optogenetic activation of the DCNVm neurons caused rapid elevated firing activity in the cingulate cortex, a brain area critical for bridging the time gap between sensory stimuli and motor execution during tEBC. Together, our data highlights DCNVm neurons' function and delineates their kinematic parameters that modulate the strength of associative sensorimotor responses.

Neuronal Activity in the Cerebellum During the Sleep-Wakefulness Transition in Mice / 神经科学通报·英文版

Cerebellar malfunction can lead to sleep disturbance such as excessive daytime sleepiness, suggesting that the cerebellum may be involved in regulating sleep and/or wakefulness. However, understanding the features of cerebellar regulation in sleep and wakefulness states requires a detailed characterization of neuronal activity within this area. By performing multiple-unit recordings in mice, we showed that Purkinje cells (PCs) in the cerebellar cortex exhibited increased firing activity prior to the transition from sleep to wakefulness. Notably, the increased PC activity resulted from the inputs of low-frequency non-PC units in the cerebellar cortex. Moreover, the increased PC activity was accompanied by decreased activity in neurons of the deep cerebellar nuclei at the non-rapid eye-movement sleep-wakefulness transition. Our results provide in vivo electrophysiological evidence that the cerebellum has the potential to actively regulate the sleep-wakefulness transition.

Effects of polydatin on learning and memory and Cdk5 kinase activity in the hippocampus of rats with chronic alcoholism / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To observe the effects of polydatin on learning and memory and cyclin-dependent kinase 5 (Cdk5) kinase activity in the hippocampus of rats with chronic alcoholism.</p><p><b>METHODS</b>Forty rats were randomly divided into 4 groups: control group, chronic alcoholism group, low and high polydatin group. The rat chronic alcoholism model was established by ethanol 3.0 g/(kg · d) (intragastric administration). The abstinence scoring was used to evaluate the rats withdrawal symptoms; cognitive function was measured by Morris water maze experiment; Cdk5 protein expression in the hippocampus was detected by immunofluorescence; Cdk5 kinase activity in the hippocampus was detected by liquid scintillation counting method.</p><p><b>RESULTS</b>The abstinence score, escape latency, Cdk5 kinase activity in chronic alcoholism group rats were significantly higher than those of control group (P < 0.05). The abstinence score, escape latency in high polydatin group rats were significantly lower than those of chronic alcoholism group (P < 0.05); Cdk5 kinase activity in high and low polydatin group rats was significantly lower than that of chronic alcoholism group( P < 0.05); immunofluorescence showed that the Cdk5 positive cells of chronic alcoholism group were significantly increased compared with control group (P < 0.05), and the Cdk5 positive cells of polydatin groups were significantly decreased compared with chronic alcoholism group ( P < 0.05).</p><p><b>CONCLUSION</b>Polydatin-reduced the chronic alcoholism damage may interrelate with regulation of Cdk5 kinase activity.</p>

Effects of acute cooling/rewarming on membrane potential and K(+) currents in rat ventricular myocytes / 生理学报

The effects of acute cooling/rewarming on cardiac K(+) currents and membrane potential were investigated. Membrane potential and current were assessed with whole-cell patch-clamp technique in current- and voltage-clamp modes. When the temperature of bath solution was decreased from 25 °C; to 4 °C, the transient outward current (I(to)) was completely abolished, the sustained outward K(+) current (I(ss)) at +60 mV and the inward rectifier K(+) current (I(K1)) at -120 mV were depressed by (48.5±14.1)% and (35.7±18.2)%, respectively, and the membrane potential became more positive. After the temperature of bath solution was raised from 4 °C; to 36 °C;, the membrane potential exhibited a transient hyperpolarization and then was maintained at a stable level. In some myocytes (36 out of 58), activation of the ATP-sensitive K(+) (K(ATP)) channels after rewarming was observed. The rewarming-induced change in the membrane potential was inhibited by the Na(+)/K(+)-ATPase inhibitor ouabain (100 μmol/L), and the rewarming-elicited activation of K(ATP) channels was inhibited by the protein kinase A inhibitor H-89 (100 μmol/L). Moreover, decrease of the temperature from 25 °C; to 4 °C; did not induce any significant change in cell volume when the cell membrane potential was clamped at 0 mV. However, significant cell shrinkage with spots was observed soon after rewarming-induced activation of K(ATP) channels. These data demonstrate that acute cooling/rewarming has a profound influence on the membrane potential and K(+) currents of ventricular myocytes, and suggest that activation of K(ATP) channels may play a role in cardiac cooling/rewarming injury.

Inhibitory effect of melatonin on oxidative stress i n kidneys of diabetic rats / 中华内分泌代谢杂志

Objective To in ve stigate the effects of melatonin on oxidative stress and renal function in kidne ys of diabetic rats. Methods Diabetic model of rats was induced by streptozocin. Male diabetic SD rats were assigned to 3 group s: (1) Untreated (DMC); (2) DM+Mel 1, melatonin 0.2 mg?kg -1 ?d -1 b y gavage, and (3) DM+Mel 2, melatonin 5 mg?kg -1 ?d -1 by gavage, se ven rats were in each group. Seven normal rats were assigned to normal control ( NC) group. Eight weeks later, systemic and renal intrinsic anti-oxidant enzyme activities, lipid peroxide levels and urinary protein excretion, creatinine clea rance rate and kidney weight were evaluated. Results Glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities were lower and lipid peroxide levels were higher in renal cortex of diabetic ra ts than those in NC group. SOD and GSH-Px activities in renal cortex increased and plasma triglycerides level and urinary protein excretion decreased in DM+Mel 1 group. DM+Mel 2 group showed changes similar to DM+Mel 1 group. These dose s also reduced lipid peroxide levels in renal cortex and kidney weight/body weig ht ratio of diabetic rats. Moreover, larger dose melatonin reversed the lowered SODactivitiesine rythrocytesand the raised lipid peroxide levels in plasma of dia betic rats. Conclusion Melatonin may inhibit oxi dative stress in kidneys and improve renal function in diabetic rats. Overproduc tion of reactive oxygen free radicals and insufficieny in intrinsic anti-oxidan t enzymes may contribute to the development of diabetic nephropathy.