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Objective To explore the different effects of rapid hypothermia on the electrophysiological characteristics of pyramidal neurons and interneurons in epileptic patients. Methods A total of 13 brain tissue samples were selected from patients with focal drug ⁃ resistant epilepsy who underwent epileptogenic lesion resection in Department of Functional Neurosurgery, Xuanwu Hospital, Capital Medical University from June to December 2016. Using perfusion method, the brain tissue slice temperature was quickly reduced to 20 ℃ in a step manner, then rewarmed to 30 ℃, and maintained at 30 ℃ for 10 min (the target temperature was changed by 5 ℃ every 10 min). Patch clamping technique was used to record the resting membrane potential, synaptic activity and action potential of pyramidal neurons (n=18) and interneurons (n=6) in epileptic cerebral cortex. Results 1) Resting membrane potential: when the temperature dropped to 20 ℃, the resting membrane potential of the two kinds of neurons showed slight depolarization, but there was no statistical significance in the changes of resting membrane potential at different temperatures and the changes of resting membrane potential of the two kinds of neurons at the same temperature (P＞0.05, for all). 2) Synaptic activity: after cooling, the amplitude of excitatory postsynaptic current (EPSC) of interneuron was smaller (F=5.332, P=0.034). The normalized percentages of EPSC (F=8.811, P=0.000) and inhibitory postsynaptic current (IPSC; F=9.843, P=0.000) amplitude, EPSC event interval (F=7.065, P=0.001), EPSC (F=6.281, P=0.002) and IPSC (F=8.266, P=0.000) peak area were statistically significant. 3) Action potential: there were no significant differences in the effects of temperature change on the normalized percentages of the threshold, frequency, amplitude and half⁃width time of the action potential of the two kinds of neurons (P＞0.05, for all). However, the differences of normalized percentages of action potential frequency (F=4.801, P=0.008), amplitude (F=3.680, P=0.015) and half⁃width time (F=28.951, P=0.000) of neuronal action potentials at different temperatures were statistically significant. Conclusions When the temperature was reduced to 20 ℃, the electrophysiological activities of the two kinds of neurons were significantly inhibited. The inhibition of EPSC amplitude of synaptic activity in interneurons was stronger than that in pyramidal neurons. Inhibition of interneuron activity may be one of the reasons for hypothermia prevention and termination of epilepsy.

Objective: To explore the changes in the excitatory/inhibitory (E/I) balance of pyramidal neurons in prefrontal cortex and hippocampus in mice with anxiety disorder induced by chronic unpredictable mild stress (CUMS). Methods: Twenty-four C57/BL6 male mice were randomly divided into control group (CTRL) and model group (CUMS), with 12 mice in each group. The mice in CUMS group were subjected to 21 days of stress, including restraint for 1 h, reversed day/night cycle for 24 h, forced warm water bath for 5 min, water/food deprivation for 24 h, housing in wet sawdust for 18 h, shaking the cage for 30 min, noise for 1 h, and social stress for 10 min. CTRL group mice were fed normally. Anxiety-related behavioral tests and whole-cell recording tests were performed after modeling. Results: Compared with CTRL group, the time of spent in the central arena of CUMS group was reduced significantly in open field test ( P ＜0.01), the time and number of entering the open arms were decreased significantly in elevated plus maze test ( P ＜0.01), and the time of staying in the closed arms was increased significantly in CUMS group ( P ＜0.01). The sEPSC frequency, capacitance and E/I ratio of dlPFC, mPFC and vCA1 pyramidal neurons of mice in CUMS group were increased significantly ( P ＜0.01), while sEPSC amplitude, sIPSC frequency, amplitude and capacitance were not significantly changed ( P ＞0.05). The frequency, amplitude, capacitance and E/I ratio of sEPSC and sIPSC of dCA1 pyramidal neurons were not significantly changed ( P ＞0.05). Conclusion: The anxiety-like behavior of CUMS-induced mice may be the result of the participation of multiple brain regions, which is mainly related to the increase of the excitability of pyramidal neurons in dlPFC, mPFC and vCA1 brain regions, but seems to have little relationship with dCA1 brain regions.

Objective: To investigate the effects of acid-sensing ion channels (ASICs) on electrophysiological epileptic activities of mouse hippocampal pyramidal neurons in the extracellular acidotic condition., Methods: We investigated effects of extracellular acidosis on epileptic activities induced by elevated extracellular K + concentration or the application of an antagonist of GABA A receptors in perfusate of mouse hippocampal slices under field potential recordings. We also tested the effects of extracellular acidosis on neuronal excitability under field potential recording and evaluated the changes in epileptic activities of the neurons in response to pharmacological inhibition of ASICs using a specific inhibitor of ASICs., Results: Extracellular acidosis significantly suppressed epileptic activities of the hippocampal neurons by converting ictal-like epileptic activities to non-ictal-like epileptic activities in both high [K + ]o and disinhibition models, and also suppressed the intrinsic excitability of the neurons. ASICs inhibitor did not antagonize the inhibitory effect of extracellular acidosis on ictal epileptic activities and intrinsic neuronal excitability, but exacerbated non-ictal epileptic activities of the neurons in extracellular acidotic condition in both high [K + ]o and disinhibition models., Conclusions: ASICs can differentially modulate ictal-like and non-ictallike epileptic activities via its direct actions on excitatory neurons.

GABAergic interneurons are neurons that mainly release the neurotransmitter of γ-aminobutyric acid (GABA), accounting for approximately 20% of the total number of neurons in the cerebral cortex. They form wide synaptic connections with the pyramidal cells and regulate the pyramidal activity, playing an important role in maintenance of excitation/inhibition balance in cortical circuits. Recently, studies have shown that GABAergic interneurons dysfunction is the key mechanism underlying neuropsychiatric disorders such as schizophrenia, depression, and autism. N-methyl- D -aspartic acid (NMDA) receptors are the main receptors in GABAergic interneurons, and its dysfunction and different subunit deletions can mediate GABAergic interneuron dysfunction.

The etiology of attention-deficit hyperactivity disorder (ADHD) has been generally linked to the decrease in cortex activity, as well as to the reduction in dopamine (DA) and norepinephrine (NE) levels. Methylphenidate (MPH; Ritalin) is the most commonly prescribed medication for ADHD. It has been determined that MPH acts primarily on the dopaminergic and noradrenergic systems through blockade of DA and NE transporters, thereby increasing the concentrations of these neurotransmitters in the brain to correct the attention deficits and hyperactivity. In addition, MPH has been proposed to increase the excitability of pyramidal neurons and the overall activity of cortex. However, the effect of MPH on the activity of interneurons is lack of investigation. Here, by using immunohistochemistry technique, we examined c-Fos expression in parvalbumin (PV)-expressing interneurons of frontal cortex of rats (28-day-old) at 1 h after a single MPH infusion (1 or 8 mg/kg; s.c.). We analyzed the c-Fos expression in the medial orbitofrontal cortex (MO), ventral orbitofrontal cortex (VO), and lateral orbitofrontal cortex (LO) subregions of orbitofrontal cortex (OFC), as well as the prelimbic cortex (PrL) and infralimbic cortex (IL) subregions of the prefrontal cortex (PFC) and anterior cingulate cortex (ACC) after MPH infusion. Our data showed that MPH increased c-Fos expression in MO, VO and LO, and the c-Fos expression in PV-expressing interneurons elevated significantly in MO, VO, but not in LO. Meanwhile, the increases of c-Fos expression in PrL and IL, as well as in PV-expressing interneurons of these two regions, were only induced by 1 mg/kg MPH, but not 8 mg/kg. Both 1 and 8 mg/kg MPH dramatically increased c-Fos expression in ACC, especially, in PV-expressing interneurons of ACC as well. In conclusion, acute systemic injection of MPH significantly increases the c-Fos expression in PV-expressing interneurons of the OFC, PFC and ACC.