Neural Mechanism Underlying Task-Specific Enhancement of Motor Learning by Concurrent Transcranial Direct Current Stimulation / 神经科学通报·英文版

The optimal protocol for neuromodulation by transcranial direct current stimulation (tDCS) remains unclear. Using the rotarod paradigm, we found that mouse motor learning was enhanced by anodal tDCS (3.2 mA/cm2) during but not before or after the performance of a task. Dual-task experiments showed that motor learning enhancement was specific to the task accompanied by anodal tDCS. Studies using a mouse model of stroke induced by middle cerebral artery occlusion showed that concurrent anodal tDCS restored motor learning capability in a task-specific manner. Transcranial in vivo Ca2+ imaging further showed that anodal tDCS elevated and cathodal tDCS suppressed neuronal activity in the primary motor cortex (M1). Anodal tDCS specifically promoted the activity of task-related M1 neurons during task performance, suggesting that elevated Hebbian synaptic potentiation in task-activated circuits accounts for the motor learning enhancement. Thus, application of tDCS concurrent with the targeted behavioral dysfunction could be an effective approach to treating brain disorders.

Revealing the Precise Role of Calretinin Neurons in Epilepsy: We Are on the Way / 神经科学通报·英文版

Epilepsy is a common neurological disorder characterized by hyperexcitability in the brain. Its pathogenesis is classically associated with an imbalance of excitatory and inhibitory neurons. Calretinin (CR) is one of the three major types of calcium-binding proteins present in inhibitory GABAergic neurons. The functions of CR and its role in neural excitability are still unknown. Recent data suggest that CR neurons have diverse neurotransmitters, morphologies, distributions, and functions in different brain regions across various species. Notably, CR neurons in the hippocampus, amygdala, neocortex, and thalamus are extremely susceptible to excitotoxicity in the epileptic brain, but the causal relationship is unknown. In this review, we focus on the heterogeneous functions of CR neurons in different brain regions and their relationship with neural excitability and epilepsy. Importantly, we provide perspectives on future investigations of the role of CR neurons in epilepsy.

At the crossroads of epilepsy and sleep: some issues / Na encruzilhada da epilepsia e do sono: algumas questões

There is a close association between sleep and epilepsy, and this literature review aims to raise issues regarding sleep time control, circadian and ultradian rhythms, epilepsy and its interaction with sleep and circadian rhythm, epilepsy and sleep disorders, and finally epilepsy management and medications. It is mentioned that sleep may provide a hypersynchronous state, as occurs in non-rapid eye movement sleep (NREM), and hyperexcitability, in cyclic alternating pattern (CAP), allowing more frequent interictal epileptiform abnormalities and seizures. In some epilepsy syndromes, seizures occur broadly / or entirely during sleep or on awakening, mainly in childhood, and maybe exacerbated in adults during the sleep or sleep-deprived, and there are the so-called Sleep-related epilepsies that are divided as sleep-associated, sleep-accentuated and arousal/awakening related. Sleep quality may be reduced in patients with epilepsy also due to nocturnal seizures or concomitant sleep disorders. Sleep disorders are common in patients with epilepsy and treatment of them mainly sleep-disordered breathing may improve seizure control. Besides, some parasomnias may mimic seizures, and also they can adversely affect the quality and quantity of sleep whereas antiepileptic therapy can have a negative or positive effect on sleep. Nocturnal epileptic seizures may be challenging to discern from parasomnias, in particular NREM parasomnias such as night terrors, sleepwalking and confusional arousals.

Há uma estreita associação entre sono e epilepsia, e esta revisão de literatura tem como objetivo levantar questões relacionadas ao controle do tempo do sono, ritmos circadianos e ultradianos, epilepsia e sua interação com sono e ritmo circadiano, epilepsia e transtornos do sono e, finalmente, o tratamento e medicamentos para epilepsia. Menciona-se que o sono pode proporcionar um estado hipersincrônico, como ocorre no sono "non-rapid eye movement" (NREM), e hiperexcitabilidade, no "cyclic alternating pattern" (CAP), permitindo anormalidades epileptiformes interictais e crises epilépticas mais frequentes. Em algumas síndromes epilépticas, as crises ocorrem ampla / ou inteiramente durante o sono ou despertar, principalmente na infância, e podem ser exacerbadas em adultos durante o sono ou privação de sono, e as chamadas epilepsias relacionadas ao sono se dividem em sono associadas, sono acentuadas e relacionadas com o despertar. A qualidade do sono pode ser reduzida em pacientes com epilepsia também devido a crises epilépticas noturnas ou transtornos do sono concomitantes. Esses são comuns em pacientes com epilepsia e o seu tratamento, principalmente dos transtornos respiratórios do sono, pode melhorar o controle das crises epilépticas. Além disso, algumas parassonias podem mimetizar crises epilépticas, e também elas podem afetar adversamente a qualidade e a quantidade do sono, enquanto a terapia antiepiléptica pode ter um efeito negativo ou positivo sobre o sono. Pode ser difícil discernir as crises epilépticas noturnas das parassonias, em particular das parassonias NREM, como terrores noturnos, crises de sonambulismo e despertares confusionais.

Recent advances in understanding the roles and molecular mechanisms of cannabidiol in neuropsychiatric disorders / 药学学报

italic>Cannabis sativa, one of the ancient medicinal plants, has been used to alleviate pain and seizures. However, cannabinoids are often addictive, which limits their clinical use. Cannabidiol (CBD) as a non-psychoactive component of Cannabis sativa, has much weaker adverse effects than Δ9-tetrahydrocannabinol (THC) and therefore has received widespread attention. CBD has been found to ameliorate a variety of neuropsychiatric diseases, but the precise mechanism(s) of action are still unclear. Due to its low affinity for classical cannabinoid receptors current studies are focusing on other targets outside the endocannabinoid system. In the present review we mainly summarize the effects and molecular mechanisms of CBD in neuropsychiatric disorders, including epilepsy, neuropathic pain, anxiety, and depression.

Cyproheptadine Regulates Pyramidal Neuron Excitability in Mouse Medial Prefrontal Cortex / 神经科学通报·英文版

Cyproheptadine (CPH), a first-generation antihistamine, enhances the delayed rectifier outward K current (I) in mouse cortical neurons through a sigma-1 receptor-mediated protein kinase A pathway. In this study, we aimed to determine the effects of CPH on neuronal excitability in current-clamped pyramidal neurons in mouse medial prefrontal cortex slices. CPH (10 µmol/L) significantly reduced the current density required to generate action potentials (APs) and increased the instantaneous frequency evoked by a depolarizing current. CPH also depolarized the resting membrane potential (RMP), decreased the delay time to elicit an AP, and reduced the spike threshold potential. This effect of CPH was mimicked by a sigma-1 receptor agonist and eliminated by an antagonist. Application of tetraethylammonium (TEA) to block I channels hyperpolarized the RMP and reduced the instantaneous frequency of APs. TEA eliminated the effects of CPH on AP frequency and delay time, but had no effect on spike threshold or RMP. The current-voltage relationship showed that CPH increased the membrane depolarization in response to positive current pulses and hyperpolarization in response to negative current pulses, suggesting that other types of membrane ion channels might also be affected by CPH. These results suggest that CPH increases the excitability of medial prefrontal cortex neurons by regulating TEA-sensitive I channels as well as other TEA-insensitive K channels, probably I and inward-rectifier Kir channels. This effect of CPH may explain its apparent clinical efficacy as an antidepressant and antipsychotic.

Effect of Neuronal Excitability in Hippocampal CA1 Area on Auditory Pathway in a Rat Model of Tinnitus / 中华医学杂志(英文版)

Background@#Tinnitus is a common disorder that causes significant morbidity; however, the neurophysiological mechanism is not yet fully understood. A relationship between tinnitus and limbic system has been reported. As a significant component of the limbic system, the hippocampus plays an important role in various pathological processes, such as emotional disturbance, decreased learning ability, and deterioration of memory. This study was aimed to explore the role of the hippocampus in the generation of tinnitus by electrophysiological technology.@*Methods@#A tinnitus model was established in rats through intraperitoneal injection of salicylate (SA). Subsequently, the spontaneous firing rate (SFR) of neurons in the hippocampal CA1 area was recorded with in vivo multichannel recording technology to assess changes in excitability induced by SA. To investigate the effect of excitability changes of hippocampus on the auditory pathway, the hippocampus was electrically stimulated and neural excitability in the auditory cortex (AC) was monitored.@*Results@#Totally 65 neurons in the hippocampal CA1 area were recorded, 45 from the SA group (n = 5), and 20 from the saline group (n = 5). Two hours after treatment, mean SFR of neurons in the hippocampal CA1 area had significantly increased from 3.06 ± 0.36 Hz to 9.18 ± 1.30 Hz in the SA group (t = -4.521, P 0.05). In the AC, 79.3% (157/198) of recorded neurons showed responses to electrical stimulation of the hippocampal CA1 area. Presumed pyramidal neurons were excited, while intermediate neurons were inhibited after electrical stimulation of the hippocampus.@*Conclusions@#The study shows that the hippocampus is excited in SA-induced tinnitus, and stimulation of hippocampus could modulate neuronal excitability of the AC. The hippocampus is involved in tinnitus and may also have a regulatory effect on the neural center.

Cognitive impairment and neural electrophysiological studies in early stage of transgenic Alzheimer's disease mice / 中华行为医学与脑科学杂志

Objective To investigate the early onset of learning and memory function of 4-month-old APP/PS1/Tau Alzheimer' s disease (3×Tg-AD) model mice and explore the pathogenesis of AD in early stage through evaluating neuron excitability and BKCa channel activity in cingulate cortex pyramidal cells.Methods Ten 4-month-old male 3×Tg-AD mice and matched ten wild type (WT) mice.Behavior was tested with the novel object recognition task to observe the ability of learning and memory.Whole-cell patch-clamp recordings were performed to assess the excitability of cingulate cortex pyramidal cells in terms of resting membrane potential and frequencies of spikes evoked by current injection.A train of five pulses of depolarizing currents were injected at 100 Hz to assess the spike width,which was used as an index for BKCa channel activity.Results Compared with the WT group (0.72±0.03),the novel object recognition index significantly decreased in 3 × Tg-AD group (0.55 ± 0.04) (P =0.004).Compared to the WT group((-66.03±0.43) mV),the resting membrane potential in cingulate cortex neurons of 3×Tg-AD group((-62.31±0.54)mV) was significantly depolarized(P=0.000).In contrast to WT group,the action potential firing frequencies evoked by depolarizing current injections were higher in neurons from 3×Tg-AD group(P=0.000),demonstrating that excitability of cingulate cortex neurons was elevated by intracellular Aβ.Spikes were broader in the 3×Tg-AD group than those in the WT group(P＜0.01).Suppression of BKCa channels in cingulate cortex neurons from the 3×Tg-AD group was confirmed on the basis of the spike half-width,since BKCa channels affect the descending phase of spikes.Conclusion Compared to WT mice,4-month-old 3×Tg-AD mice are impaired in learning and memory.The suppression of BKCa channels by intracellular Aβ leads to increase of excitability in cingulate cortex pyramidal cells.

Remembering Obaid Siddiqi, a pioneer in the study of temperature-sensitive paralytic mutants in Drosophila.

Although Obaid Siddiqi’s major research focus in neurogenetics was on chemosensation and olfaction in Drosophila, he made seminal contributions to the study of temperature-sensitive paralytic mutants that paved the way for research that we and many other investigators have continued to pursue. Here we recount Siddiqi’s investigation and the impact it had on our own studies especially at a formative stage of our careers. We acknowledge our debt to Obaid Siddiqi and remember him fondly as an inspired and inspiring scientist, mentor, role model and human being.