Browsing by Subject "Electrophysiological Phenomena"

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    Chemogenetics-mediated acute inhibition of excitatory neuronal activity improves stroke outcome.
    (Experimental neurology, 2020-04) Wang, Ya-Chao; Galeffi, Francesca; Wang, Wei; Li, Xuan; Lu, Liping; Sheng, Huaxin; Hoffmann, Ulrike; Turner, Dennis A; Yang, Wei

    Background and purpose

    Ischemic stroke significantly perturbs neuronal homeostasis leading to a cascade of pathologic events causing brain damage. In this study, we assessed acute stroke outcome after chemogenetic inhibition of forebrain excitatory neuronal activity.

    Methods

    We generated hM4Di-TG transgenic mice expressing the inhibitory hM4Di, a Designer Receptors Exclusively Activated by Designer Drugs (DREADD)-based chemogenetic receptor, in forebrain excitatory neurons. Clozapine-N-oxide (CNO) was used to activate hM4Di DREADD. Ischemic stroke was induced by transient occlusion of the middle cerebral artery. Neurologic function and infarct volumes were evaluated. Excitatory neuronal suppression in the hM4Di-TG mouse forebrain was assessed electrophysiologically in vitro and in vivo, based on evoked synaptic responses, and in vivo based on occurrence of potassium-induced cortical spreading depolarizations.

    Results

    Detailed characterization of hM4Di-TG mice confirmed that evoked synaptic responses in both in vitro hippocampal slices and in vivo motor cortex were significantly reduced after CNO-mediated activation of the inhibitory hM4Di DREADD. Further, CNO treatment had no obvious effects on physiology and motor function in either control or hM4Di-TG mice. Importantly, hM4Di-TG mice treated with CNO at either 10 min before ischemia or 30 min after reperfusion exhibited significantly improved neurologic function and smaller infarct volumes compared to CNO-treated control mice. Mechanistically, we showed that potassium-induced cortical spreading depression episodes were inhibited, including frequency and duration of DC shift, in CNO-treated hM4Di-TG mice.

    Conclusions

    Our data demonstrate that acute inhibition of a subset of excitatory neurons after ischemic stroke can prevent brain injury and improve functional outcome. This study, together with the previous work in optogenetic neuronal modulation during the chronic phase of stroke, supports the notion that targeting neuronal activity is a promising strategy in stroke therapy.
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    Differences in mismatch responses to vowels and musical intervals: MEG evidence.
    (PLoS One, 2013) Bergelson, Elika; Shvartsman, Michael; Idsardi, William J
    We investigated the electrophysiological response to matched two-formant vowels and two-note musical intervals, with the goal of examining whether music is processed differently from language in early cortical responses. Using magnetoencephalography (MEG), we compared the mismatch-response (MMN/MMF, an early, pre-attentive difference-detector occurring approximately 200 ms post-onset) to musical intervals and vowels composed of matched frequencies. Participants heard blocks of two stimuli in a passive oddball paradigm in one of three conditions: sine waves, piano tones and vowels. In each condition, participants heard two-formant vowels or musical intervals whose frequencies were 11, 12, or 24 semitones apart. In music, 12 semitones and 24 semitones are perceived as highly similar intervals (one and two octaves, respectively), while in speech 12 semitones and 11 semitones formant separations are perceived as highly similar (both variants of the vowel in 'cut'). Our results indicate that the MMN response mirrors the perceptual one: larger MMNs were elicited for the 12-11 pairing in the music conditions than in the language condition; conversely, larger MMNs were elicited to the 12-24 pairing in the language condition that in the music conditions, suggesting that within 250 ms of hearing complex auditory stimuli, the neural computation of similarity, just as the behavioral one, differs significantly depending on whether the context is music or speech.
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    Electrophysiological Biomarkers Predict Clinical Improvement in an Open-Label Trial Assessing Efficacy of Autologous Umbilical Cord Blood for Treatment of Autism.
    (Stem cells translational medicine, 2018-11) Murias, Michael; Major, Samantha; Compton, Scott; Buttinger, Jessica; Sun, Jessica M; Kurtzberg, Joanne; Dawson, Geraldine
    This study was a phase I, single-center, and open-label trial of a single intravenous infusion of autologous umbilical cord blood in young children with autism spectrum disorder (ASD). Twenty-five children between the ages of 2 and 6 with a confirmed diagnosis of ASD and a qualified banked autologous umbilical cord blood unit were enrolled. Safety results and clinical outcomes measured at 6 and 12 months post-infusion have been previously published. The purpose of the present analysis was to explore whether measures of electroencephalography (EEG) theta, alpha, and beta power showed evidence of change after treatment and whether baseline EEG characteristics were predictive of clinical improvement. The primary endpoint was the parent-reported Vineland adaptive behavior scales-II socialization subscale score, collected at baseline, 6- and 12-month visits. In addition, the expressive one word picture vocabulary test 4 and the clinical global impression-improvement scale were administered. Electrophysiological recordings were taken during viewing of dynamic social and nonsocial stimuli at 6 and 12 months post-treatment. Significant changes in EEG spectral characteristics were found by 12 months post-infusion, which were characterized by increased alpha and beta power and decreased EEG theta power. Furthermore, higher baseline posterior EEG beta power was associated with a greater degree of improvement in social communication symptoms, highlighting the potential for an EEG biomarker to predict variation in outcome. Taken together, the results suggest that EEG measures may be useful endpoints for future ASD clinical trials. Stem Cells Translational Medicine 2018;7:783-791.
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    Freezing behaviour facilitates bioelectric crypsis in cuttlefish faced with predation risk.
    (Proc Biol Sci, 2015-12-07) Bedore, Christine N; Kajiura, Stephen M; Johnsen, Sönke
    Cephalopods, and in particular the cuttlefish Sepia officinalis, are common models for studies of camouflage and predator avoidance behaviour. Preventing detection by predators is especially important to this group of animals, most of which are soft-bodied, lack physical defences, and are subject to both visually and non-visually mediated detection. Here, we report a novel cryptic mechanism in S. officinalis in which bioelectric cues are reduced via a behavioural freeze response to a predator stimulus. The reduction of bioelectric fields created by the freeze-simulating stimulus resulted in a possible decrease in shark predation risk by reducing detectability. The freeze response may also facilitate other non-visual cryptic mechanisms to lower predation risk from a wide range of predator types.
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    Identification of a Retinal Circuit for Recurrent Suppression Using Indirect Electrical Imaging.
    (Current biology : CB, 2016-08) Greschner, Martin; Heitman, Alexander K; Field, Greg D; Li, Peter H; Ahn, Daniel; Sher, Alexander; Litke, Alan M; Chichilnisky, EJ
    Understanding the function of modulatory interneuron networks is a major challenge, because such networks typically operate over long spatial scales and involve many neurons of different types. Here, we use an indirect electrical imaging method to reveal the function of a spatially extended, recurrent retinal circuit composed of two cell types. This recurrent circuit produces peripheral response suppression of early visual signals in the primate magnocellular visual pathway. We identify a type of polyaxonal amacrine cell physiologically via its distinctive electrical signature, revealed by electrical coupling with ON parasol retinal ganglion cells recorded using a large-scale multi-electrode array. Coupling causes the amacrine cells to fire spikes that propagate radially over long distances, producing GABA-ergic inhibition of other ON parasol cells recorded near the amacrine cell axonal projections. We propose and test a model for the function of this amacrine cell type, in which the extra-classical receptive field of ON parasol cells is formed by reciprocal inhibition from other ON parasol cells in the periphery, via the electrically coupled amacrine cell network.
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    Monte Carlo methods for localization of cones given multielectrode retinal ganglion cell recordings.
    (Network (Bristol, England), 2013-01) Sadeghi, K; Gauthier, JL; Field, GD; Greschner, M; Agne, M; Chichilnisky, EJ; Paninski, L
    It has recently become possible to identify cone photoreceptors in primate retina from multi-electrode recordings of ganglion cell spiking driven by visual stimuli of sufficiently high spatial resolution. In this paper we present a statistical approach to the problem of identifying the number, locations, and color types of the cones observed in this type of experiment. We develop an adaptive Markov Chain Monte Carlo (MCMC) method that explores the space of cone configurations, using a Linear-Nonlinear-Poisson (LNP) encoding model of ganglion cell spiking output, while analytically integrating out the functional weights between cones and ganglion cells. This method provides information about our posterior certainty about the inferred cone properties, and additionally leads to improvements in both the speed and quality of the inferred cone maps, compared to earlier "greedy" computational approaches.
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    Single neuron dynamics and computation.
    (Current opinion in neurobiology, 2014-04) Brunel, Nicolas; Hakim, Vincent; Richardson, Magnus JE
    At the single neuron level, information processing involves the transformation of input spike trains into an appropriate output spike train. Building upon the classical view of a neuron as a threshold device, models have been developed in recent years that take into account the diverse electrophysiological make-up of neurons and accurately describe their input-output relations. Here, we review these recent advances and survey the computational roles that they have uncovered for various electrophysiological properties, for dendritic arbor anatomy as well as for short-term synaptic plasticity.
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    Transcription factors MYOCD, SRF, Mesp1 and SMARCD3 enhance the cardio-inducing effect of GATA4, TBX5, and MEF2C during direct cellular reprogramming.
    (PLoS One, 2013) Christoforou, Nicolas; Chellappan, Malathi; Adler, Andrew F; Kirkton, Robert D; Kirkton, Robert D; Wu, Tianyi; Addis, Russell C; Bursac, Nenad; Leong, Kam W
    Transient overexpression of defined combinations of master regulator genes can effectively induce cellular reprogramming: the acquisition of an alternative predicted phenotype from a differentiated cell lineage. This can be of particular importance in cardiac regenerative medicine wherein the heart lacks the capacity to heal itself, but simultaneously contains a large pool of fibroblasts. In this study we determined the cardio-inducing capacity of ten transcription factors to actuate cellular reprogramming of mouse embryonic fibroblasts into cardiomyocyte-like cells. Overexpression of transcription factors MYOCD and SRF alone or in conjunction with Mesp1 and SMARCD3 enhanced the basal but necessary cardio-inducing effect of the previously reported GATA4, TBX5, and MEF2C. In particular, combinations of five or seven transcription factors enhanced the activation of cardiac reporter vectors, and induced an upregulation of cardiac-specific genes. Global gene expression analysis also demonstrated a significantly greater cardio-inducing effect when the transcription factors MYOCD and SRF were used. Detection of cross-striated cells was highly dependent on the cell culture conditions and was enhanced by the addition of valproic acid and JAK inhibitor. Although we detected Ca(2+) transient oscillations in the reprogrammed cells, we did not detect significant changes in resting membrane potential or spontaneously contracting cells. This study further elucidates the cardio-inducing effect of the transcriptional networks involved in cardiac cellular reprogramming, contributing to the ongoing rational design of a robust protocol required for cardiac regenerative therapies.