L-type Ca2+ channels and charybdotoxin-sensitive Ca2+-activated K+ channels are required for reduction of GABAergic activity induced by ß2-adrenoceptor in the prefrontal cortex.

Whereas ß2-adrenoceptor (ß2-AR) has been reported to reduce GABAergic activity in the prefrontal cortex (PFC), the underlying cellular and molecular mechanisms have not been completely determined. Here, we showed that ß2-AR agonist Clenbuterol (Clen) decreased GABAergic transmission onto PFC layer V/VI pyramidal neurons via a presynaptic mechanism without altering postsynaptic GABA receptors. Clen decreased the action potential firing rate but increased the burst afterhyperpolarization (AHP) amplitude in PFC interneurons. Application of L-type Ca2+ channel or charybdotoxin-sensitive Ca2+-activated K+ channel inhibitors blocked Clen-induced decreases in action potential firing rate, spontaneous inhibitory postsynaptic current (sIPSC) frequency and Clen-induced enhancement of AHP amplitude, suggesting that the effects of Clen involves L-type Ca2+ Channels and charybdotoxin-sensitive Ca2+-activated K+ channels. Our results provide a potential cellular mechanism by which Clen controls GABAergic neuronal activity in PFC.

NRG1-ErbB4 signaling promotes functional recovery in a murine model of traumatic brain injury via regulation of GABA release.

Traumatic brain injury (TBI) is a serious health problem in the world. However, little is known about the pathogenesis and molecular mechanisms of TBI. Here, we show that TBI activates neuregulin 1 (NRG1)-ErbB4 signaling, with an increased expression of NRG1 and ErbB4 in the traumatic region. Specifically knocking out ErbB4 in parvalbumin-positive (PV+) interneurons exacerbates motor function deficits in mice after TBI. Consistently, PV-ErbB4-/- mice showed larger necrotic area and more edema when compared with PV-ErbB4+/+ mice. Replenishment of NRG1 through intranasal application of the recombinant protein in PV-ErbB4+/+ mice enhanced neurological function. Moreover, using an in vitro neuronal culture system, we found that NRG1-ErbB4 signaling protects neurons from glutamate-induced death, and such protective effects could be diminished by GABA receptor antagonist. These results indicate that NRG-ErbB4 signaling protects cortical neurons from TBI-induced damage, and such effect is probably mediated by promoting GABA activity. Taken together, these findings unveil a previously unappreciated role for NRG1-ErB4 signaling in preventing neuronal cell death during functional recovery after TBI.

Phenylephrine enhances glutamate release in the medial prefrontal cortex through interaction with N-type Ca2+ channels and release machinery.

α1 -adrenoceptors (α1 -ARs) stimulation has been found to enhance excitatory processes in many brain regions. A recent study in our laboratory showed that α1 -ARs stimulation enhances glutamatergic transmission via both pre- and post-synaptic mechanisms in layer V/VI pyramidal cells of the rat medial prefrontal cortex (mPFC). However, a number of pre-synaptic mechanisms may contribute to α1 -ARs-induced enhancement of glutamate release. In this study, we blocked the possible post-synaptic action mediated by α1 -ARs to investigate how α1 -ARs activation regulates pre-synaptic glutamate release in layer V/VI pyramidal neurons of mPFC. We found that the α1 -ARs agonist phenylephrine (Phe) induced a significant enhancement of glutamatergic transmission. The Phe-induced potentiation was mediated by enhancing pre-synaptic glutamate release probability and increasing the number of release vesicles via a protein kinase C-dependent pathway. The mechanisms of Phe-induced potentiation included interaction with both glutamate release machinery and N-type Ca(2+) channels, probably via a pre-synaptic Gq /phospholipase C/protein kinase C pathway. Our results may provide a cellular and molecular mechanism that helps explain α1 -ARs-mediated influence on PFC cognitive functions. Alpha1 -adrenoceptor (α1 -ARs) stimulation has been reported to enhance glutamatergic transmission in layer V/VI pyramidal neurons of the rat medial prefrontal cortex (mPFC). We found that α1 -ARs agonist phenylephrine (Phe) increases pre-synaptic glutamate release probability and the number of released vesicles via interaction with both glutamate release machinery and N-type Ca(2+) channels. Our results may provide a cellular and molecular mechanism that helps explain α1 -ARs-mediated influence on PFC cognitive functions. Gq, Gq protein; PLC, phospholipase C; PKC, protein kinase C; AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; NMDA, N-methyl-d-aspartate; Glu, glutamate; Phe, phenylephrine.

Nystagmus patterns classification framework based on deep learning and optical flow.

Benign paroxysmal positional vertigo (BPPV) is the most common vestibular peripheral vertigo disease characterized by brief recurrent vertigo with positional nystagmus. Clinically, it is common to recognize the patterns of nystagmus by analyzing infrared nystagmus videos of patients. However, the existing approaches cannot effectively recognize different patterns of nystagmus, especially the torsional nystagmus. To improve the performance of recognizing different nystagmus patterns, this paper contributes an automatic recognizing method of BPPV nystagmus patterns based on deep learning and optical flow to assist doctors in analyzing the types of BPPV. Firstly, we present an adaptive method for eliminating invalid frames that caused by eyelid occlusion or blinking in nystagmus videos and an adaptive method for segmenting the iris and pupil area from video frames quickly and efficiently. Then, we use a deep learning-based optical flow method to extract nystagmus information. Finally, we propose a nystagmus video classification network (NVCN) to categorize the patterns of nystagmus. We use ConvNeXt to extract eye movement features and then use LSTM to extract temporal features. Experiments conducted on the clinically collected datasets of infrared nystagmus videos show that the NVCN model achieves an accuracy of 94.91% and an F1 score of 93.70% on nystagmus patterns classification task as well as an accuracy of 97.75% and an F1 score of 97.48% on torsional nystagmus recognition task. The experimental results prove that the framework we propose can effectively recognize different patterns of nystagmus.

Prelimbic cortex extracellular signal-regulated kinase 1/2 activation is required for memory retrieval of long-term inhibitory avoidance.

Neural mechanism underlying memory retrieval has been extensively studied in the hippocampus and amygdala. However, little is known about the role of medial prefrontal cortex in long-term memory retrieval. We evaluate this issue in one-trial step-through inhibitory avoidance (IA) paradigm. Our results showed that, 1) inactivation of mPFC by local infusion of GABAA-receptor agonist muscimol caused severe deficits in retrieval of 1-day and 7-day but had no effects on 2-h inhibitory avoidance memory; 2) the protein level of phosphorylated-ERK1/2 in mPFC were significantly increased following retrieval of 1-day and 7-day IA memory, so did the numbers of phosphorylated-ERK (pERK) and phosphorylated-CREB (pCREB) labeled neurons; 3) intra-mPFC infusion of ERK kinase inhibitor PD98095 significantly reduced phosphorylated ERK1/2 levels and phosphorylated-ERK1/2 and phosphorylated-CREB labeled cells, and severely impaired retrieval of 7-day IA memory when the drugs were administrated 30min prior to test. The present study provides evidence that retrieval of long-lasting memory for inhibitory avoidance requires mPFC and involves the ERK-CREB signaling cascade.