Pengfei Wei

Processing of visually evoked innate fear by a non-canonical thalamic pathway

The ability of animals to respond to life-threatening stimuli is essential for survival. Although vision provides one of the major sensory inputs for detecting threats across animal species, the circuitry underlying defensive responses to visual stimuli remains poorly defined. Here, we investigate the circuitry underlying innate defensive behaviours elicited by predator-like visual stimuli in mice. Our results demonstrate that neurons in the superior colliculus (SC) are essential for a variety of acute and persistent defensive responses to overhead looming stimuli. Optogenetic mapping revealed that SC projections to the lateral posterior nucleus (LP) of the thalamus, a non-canonical polymodal sensory relay, are sufficient to mimic visually evoked fear responses. In vivo electrophysiology experiments identified a di-synaptic circuit from SC through LP to the lateral amygdale (Amg), and lesions of the Amg blocked the full range of visually evoked defensive responses. Our results reveal a novel collicular–thalamic–Amg circuit important for innate defensive responses to visual threats.

Poly(3,4-ethylenedioxythiophene)/poly(styrenesulfonate)-poly(vinyl alcohol)/ poly(acrylic acid) interpenetrating polymer networks for improving optrode-neural tissue interface in optogenetics

The field of optogenetics has been successfully used to understand the mechanisms of neuropsychiatric diseases through the precise spatial and temporal control of specific groups of neurons in a neural circuitry. However, it remains a great challenge to integrate optogenetic modulation with electrophysiological and behavioral read out methods as a means to explore the causal, temporally precise, and behaviorally relevant interactions of neurons in the specific circuits of freely behaving animals. In this study, an eight-channel chronically implantable optrode array was fabricated and modified with poly(3,4-ethylenedioxythiophene)/poly(styrenesulfonate)-poly(vinyl alcohol)/poly(acrylic acid) interpenetrating polymer networks (PEDOT/PSS-PVA/PAA IPNs) for improving the optrode-neural tissue interface. The conducting polymer-hydrogel IPN films exhibited a significantly higher capacitance and lower electrochemical impedance at 1 kHz as compared to unmodified optrode sites and showed significantly improved mechanical and electrochemical stability as compared to pure conducting polymer films. The cell attachment and neurite outgrowth of rat pheochromocytoma (PC12) cells on the IPN films were clearly observed through calcein-AM staining. Furthermore, the optrode arrays were chronically implanted into the hippocampus of SD rats after the lentiviral expression of synapsin-ChR2-EYFP, and light-evoked, frequency-dependant action potentials were obtained in freely moving animals. The electrical recording results suggested that the modified optrode arrays showed significantly reduced impedance and RMS noise and an improved SNR as compared to unmodified sites, which may have benefited from the improved electrochemical performance and biocompatibility of the deposited IPN films. All these characteristics are greatly desired in optogenetic applications, and the fabrication method of conducting polymer-hydrogel IPNs can be easily integrated with other modification methods to build a more advanced optrode-neural tissue interface.

Performance of Motor Imagery Brain-Computer Interface Based on Anodal Transcranial Direct Current Stimulation Modulation

Voluntarily modulating neural activity plays a key role in brain-computer interface (BCI). In general, the self-regulated neural activation patterns are used in the current BCI systems involving the repetitive trainings with feedback for an attempt to achieve a high-quality control performance. With the limitation posed by the training procedure in most BCI studies, the present work aims to investigate whether directly modulating the neural activity by using an external method could facilitate the BCI control. We designed an experimental paradigm that combines anodal transcranial direct current stimulation (tDCS) with a motor imagery (MI)-based feedback EEG BCI system. Thirty-two young and healthy human subjects were randomly assigned to the real and sham stimulation groups to evaluate the effect of tDCS-induced EEG pattern changes on BCI classification accuracy. Results showed that the anodal tDCS obviously induces sensorimotor rhythm (SMR)-related event-related desynchronization (ERD) pattern changes in the upper-mu (10-14 Hz) and beta (14-26 Hz) rhythm components. Both the online and offline BCI classification results demonstrate that the enhancing ERD patterns could conditionally improve BCI performance. This pilot study suggests that the tDCS is a promising method to help the users to develop reliable BCI control strategy in a relatively short time.

Optogenetic dissection of ictal propagation in the hippocampal–entorhinal cortex structures

Temporal lobe epilepsy (TLE) is one of the most common drug-resistant forms of epilepsy in adults and usually originates in the hippocampal formations. However, both the network mechanisms that support the seizure spread and the exact directions of ictal propagation remain largely unknown. Here we report the dissection of ictal propagation in the hippocampal–entorhinal cortex (HP–EC) structures using optogenetic methods in multiple brain regions of a kainic acid-induced model of TLE in VGAT-ChR2 transgenic mice. We perform highly temporally precise cross-area analyses of epileptic neuronal networks and find a feed-forward propagation pathway of ictal discharges from the dentate gyrus/hilus (DGH) to the medial entorhinal cortex, instead of a re-entrant loop. We also demonstrate that activating DGH GABAergic interneurons can significantly inhibit the spread of ictal seizures and largely rescue behavioural deficits in kainate-exposed animals. These findings may shed light on future therapeutic treatments of TLE.

Opposite monosynaptic scaling of BLP–vCA1 inputs governs hopefulness- and helplessness-modulated spatial learning and memory

Different emotional states lead to distinct behavioural consequences even when faced with the same challenging events. Emotions affect learning and memory capacities, but the underlying neurobiological mechanisms remain elusive. Here we establish models of learned helplessness (LHL) and learned hopefulness (LHF) by exposing animals to inescapable foot shocks or with anticipated avoidance trainings. The LHF animals show spatial memory potentiation with excitatory monosynaptic upscaling between posterior basolateral amygdale (BLP) and ventral hippocampal CA1 (vCA1), whereas the LHL show memory deficits with an attenuated BLP–vCA1 connection. Optogenetic disruption of BLP–vCA1 inputs abolishes the effects of LHF and impairs synaptic plasticity. By contrast, targeted BLP–vCA1 stimulation rescues the LHL-induced memory deficits and mimics the effects of LHF. BLP–vCA1 stimulation increases synaptic transmission and dendritic plasticity with the upregulation of CREB and intrasynaptic AMPA receptors in CA1. These findings indicate that opposite excitatory monosynaptic scaling of BLP–vCA1 controls LHF- and LHL-modulated spatial memory, revealing circuit-specific mechanisms linking emotions to memory.

Expression of Bcl-2 and Bax in rhesus monkey testis during germ cell apoptosis induced by testosterone undecanoate.

Apoptosis occurs spontaneously during spermatogenesis and can be induced by androgen withdrawal. However, the molecular events governing apoptosis have not been characterized. To study the molecular mechanism of apoptosis induced by a high dose of testosterone undecanoate (TU), the authors examined the temporal changes in proapoptotic Bax and antiapoptotic Bcl-2 in TU-treated monkey testes. Apoptotic cells were identified in tissue sections by in situ end labeling of fragmented DNA. The results showed that a great deal of the apoptotic cells occurred in the testes on day 30 after TU injection and that the dominant apoptotic germ cells are spermatocytes and spermatids. The expression of Bcl-2 and Bax was assessed by immunohistochemical method and Western blot. As compared with that of normal testes, the levels of Bcl-2 protein increased significantly from 7 to day 14 while that of Bax protein was almost unchanged in the testes from day 7 up to day 60 after TU treatment. Bcl-2 was localized to the spermatids in the normal testes and temporarily distributed in both the cytoplasm and nucleus of those cell types susceptible to TU-induced apoptosis on day 14 after TU injection. Therefore, it is suggested that Bax may not play a role in initiating germ cell apoptosis induced by TU injection and that the evaluation in Bcl-2 expression may represent a survival mechanism for the remaining germ cell.

A novel EMD-based Common Spatial Pattern for motor imagery brain-computer interface

Common Spatial Pattern (CSP) algorithm is a commonly used effective feature extraction method in motor imagery (MI) electroencephalogram (EEG) based brain computer interface (BCI). The motor imagery patterns extracted by CSP are associated with variations in subject-specific frequency bands power. Therefore, optimizing frequency band carrying MI intention is required by the CSP method. However, the frequency band is usually divided manually and evaluated which does make use of the EEG signal property and also with low efficiency. In this paper, we propose a novel Empirical Mode Decomposition (EMD) based CSP method to realize the data-related and adaptive frequency band selection. Specifically, the intrinsic mode functions (IMFs) decomposed from the EMD and the amplitude modulated signal by instantaneous amplitude (IA) calculated from Hilbert Transform have been fully explored and employed. Moreover, the intensive experiments have been conducted to evaluate the proposed method. From the experiment results, we observed that the EMD based CSP method enhances the classification accuracy in BCI competition IV dataset I for all subjects and a paired t-test shows a significant difference level.

Light-controlled inhibition of malignant glioma by opsin gene transfer

Glioblastomas are aggressive cancers with low survival rates and poor prognosis because of their highly proliferative and invasive capacity. In the current study, we describe a new optogenetic strategy that selectively inhibits glioma cells through light-controlled membrane depolarization and cell death. Transfer of the engineered opsin ChETA (engineered Channelrhodopsin-2 variant) gene into primary human glioma cells or cell lines, but not normal astrocytes, unexpectedly decreased cell proliferation and increased mitochondria-dependent apoptosis, upon light stimulation. These optogenetic effects were mediated by membrane depolarization-induced reductions in cyclin expression and mitochondrial transmembrane potential. Importantly, the ChETA gene transfer and light illumination in mice significantly inhibited subcutaneous and intracranial glioma growth and increased the survival of the animals bearing the glioma. These results uncover an unexpected effect of opsin ion channels on glioma cells and offer the opportunity for the first time to treat glioma using a light-controllable optogenetic approach.

Multi-unit recording with iridium oxide modified stereotrodes in Drosophila melanogaster

BACKGROUND Drosophila is a very favorable animal model for the studies of neuroscience. However, it remains a great challenge to employ electrophysiological approaches in Drosophila to study the neuronal assembly dynamics in vivo, partially due to the small size of the Drosophila brain. Small and sensitive microelectrodes for multi-unit recordings are greatly desired. NEW METHOD We fabricated micro-scale stereotrodes for electrical recordings in Drosophila melanogaster. The stereotrodes were modified with iridium oxide (IrO2) under a highly controllable deposition procedure to improve their electrochemical properties. Electrical recordings were carried out using the IrO2 stereotrodes to detect spontaneous action potentials and LFPs in vivo. RESULTS The IrO2 electrodes exhibited significantly higher capacitance and lower impedance at 1 kHz. Electrical recording with the IrO2 stereotrodes in vivo demonstrated an average signal-to-noise ratio (SNR) of 7.3 and a significantly improved LFP sensitivity. 5 types of different neurons recorded were clearly separated. Electrophysiological responses to visual and odor stimulation were also detected, respectively. COMPARISON WITH EXISTING METHOD(S) The most widely used electrodes for electrical recording in Drosophila are glass microelectrode and sharpened tungsten microelectrode, which are typically used for single-unit recordings. Although tetrode technology has been used to record multi-neuronal activities from Drosophila, the fabricated IrO2 stereotrodes possess smaller geometry size but exhibited comparable recording signal-to noise ration and better sorting quality. CONCLUSIONS The IrO2 stereotrodes are capable to meet the requirements of multi-unit recording and spike sorting, which will be a useful tool for the electrophysiology-based researches especially in Drosophila and other small animals.

Modulation effect of transcranial direct current stimulation on phase synchronization in motor imagery brain-computer interface.

Transcranial direct current stimulation (tDCS) has been demonstrated that it can enhance the cortex excitability and modulate the event-related desynchronization (ERD) in motor imagery (MI). Phase synchronization is an important signature in the brain that reflects the neural interaction and integration, which has been adopted as an important EEG pattern for Brian-Computer Interface (BCI) control. In this study, we designed an experiment paradigm and investigated whether the tDCS can modulate the phase synchronization between the primary motor cortex (M1) and the supplementary motor area (SMA) in MI. Ten healthy subjects were selected and separated into two groups randomly. They performed the left and right hand MI task in two successive sessions. According to the different groups, anodal or sham stimulation were administrated to the right side of the M1. The phase locking value (PLV), which is a reliable measurement of phase synchronization in MI, was calculated. The pre and post-stimulation normalized PLV in the left hand MI task were compared. The result manifests that the normalized PLV of the entire subjects in anodal stimulation group increases after the stimulation, which shows a statistically significant difference (paired t-test p = 0.0371, n = 5). Our study reveals that the tDCS can impact the neural coupling between different brain regions and modulate phase synchronization in MI. Moreover, intervention of phase synchronization by tDCS might contribute to the rehabilitation of people with motor disorder and neurological disorders.