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Tarcsay, G.

Publications and source records attributed to Tarcsay, G..

5 recordsLinked to original sources

UNIQUE DEFICITS IN PLACE CODING ACROSS SUBFIELDS OF THE HIPPOCAMPUS IN A MOUSE MODEL OF TEMPORAL LOBE EPILEPSY.

Structured AbstractO_ST_ABSObjectiveC_ST_ABSMemory problems are comorbid with Temporal Lobe Epilepsy (TLE). Animal models of TLE reveal impairments in spatial firing fields of hippocampal place cells, providing a potential neural substrate for memory problems. Each subfield of the hippocampus carries out unique aspects of spatial memory, yet little is known about how individual subfields are perturbed. Here, we investigated the spatial coding properties of the three major subfields of the hippocampus. MethodsSingle unit recordings were made from CA1, CA3 and the dentate gyrus (DG) of mice (N = 10, 6M/4F) induced with epilepsy using the supra-hippocampal kainate model and in control mice injected with saline (N = 6, 3M/3F). Place cell activity was measured while mice foraged in highly familiar environments to assess basic place cell properties and in novel environments to assess remapping. ResultsA lower percentage of cells were classified as place cells in CA1 of epileptic mice, whereas percentages were similar in CA3 and DG compared to control. Place fields of CA1 were less coherent, place fields of CA3 were less stable, and place fields in DG has smaller differences between in-field and out of field firing. All regions constructed new distinct maps within the first session of exposure to a novel environment, however new maps in CA3 trended toward instability. SignificanceThese results point to specific deficits within subfields of the hippocampus, which may indicate that there are different cellular and network mechanisms at play. Such heterogeneity would be predicted to contribute differently to memory deficits. Key PointsO_LICA1 exhibits place map quality problems; CA1 has fewer place cells and those remaining have reduced spatial coherence C_LIO_LICA3 exhibits place map stability problems; CA3 has lower spatial correlation within sessions and trends toward not forming stable new maps in a novel environment. C_LIO_LIDG exhibits reduced signal to noise; DG has smaller differences between in-field and out of field firing rates. C_LI

neuroscience↗

Dentate spikes comprise a continuum of relative input strength from the lateral and medial entorhinal cortex.

Hippocampal dentate spikes (DS) are synchronous population events generated in the dentate gyrus thought to support memory processing. DS are classified into type 1 (DS1) and type 2 (DS2) based on current sinks in the outer or middle molecular layer, where the axons of the lateral or medial entorhinal cortex terminate, respectively. This widely used classification method constrains DS into a bimodal distribution without properly testing whether such constraint is appropriate. Here we utilized silicon probe recordings with high spatial resolution spanning all layers of the dentate gyrus and discovered that the contribution of LEC/MEC inputs to DS follows a continuous distribution. We introduce a third type (DS3) that captures a previously unreported component of the distribution: simultaneous current sinks in the outer/middle molecular layer, suggestive of synchronized activation from the LEC/MEC which could facilitate binding. We verify DS3 in several data sets from independent laboratories and characterize their brain state dependence and neural recruitment.

neuroscience↗

Interictal spikes during spatial working memory carry helpful or distracting representations of space and have opposing impacts on performance.

In temporal lobe epilepsy, interictal spikes (IS) - hypersynchronous bursts of network activity - occur at high rates in between seizures. We sought to understand the influence of IS on working memory by recording hippocampal local field potentials from epileptic mice while they performed a delayed alternation task. We found that IS disrupted performance when they were spatially non-restricted and occurred during running. In contrast, when IS were clustered at reward locations, animals performed well. A machine learning decoding approach revealed that IS at reward sites were larger than IS elsewhere on the maze, and could be classified as occurring at specific reward locations - suggesting they carry informative content for the memory task. Finally, a spiking model revealed that spatially clustered IS preserved hippocampal replay, while spatially dispersed IS disrupted replay by causing over-generalization. Together, these results show that IS can have opposing outcomes on memory.

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Low-cost platform for multi-animal chronic local field potential video monitoring with graphical user interface (GUI) for seizure detection and behavioral scoring

Experiments employing chronic monitoring of neurophysiological signals and video are commonly used in studies of epilepsy to characterize behavioral correlates of seizures. Our objective was to design a low-cost platform that enables chronic monitoring of several animals simultaneously, synchronizes bilateral local field potential and video streams in real-time, and parses recorded data into manageable file sizes. We present a hardware solution leveraging Intan and Open Ephys acquisition systems and a software solution implemented in Bonsai. The platform was tested in 48-hour continuous recordings simultaneously from multiple mice (male and female) with chronic epilepsy. To enable seizure detection and scoring, we developed a graphical user interface (GUI) that reads the data produced by our workflow and allows a user with no coding expertise to analyze events. Our Bonsai workflow was designed to maximize flexibility for a wide variety of experimental applications, and our use of the Open Ephys acquisition board would allow for scaling recordings up to 128 channels per animal. SIGNIFICANCE STATEMENTWe present a low-cost hardware and software solution intended for multi-animal chronic seizure monitoring, that prioritizes experimental freedom, and requires no coding expertise of the user. We provide details for using an Intan adapter board to enable user freedom regarding the type of electrodes used. Video and local field potential data streams are synchronized and parsed in Bonsai - an open-source visual programming language that has pre-written libraries that allow our workflow to be adapted to other data types or to integrate with open-source toolboxes. Finally, for those intending to use our platform for seizure monitoring, we provide an accessible GUI to aid in seizure detection and behavioral scoring.

neuroscience↗

Small size of recorded neuronal structures confines the accuracy in direct axonal voltage measurements

Patch-clamp instruments including amplifier circuits and pipettes affect the recorded voltage signals. We hypothesized that realistic and complete in silico representation of recording instruments together with detailed morphology and biophysics of small recorded structures will precisely reveal signal distortions and provides a tool that predicts native signals from distorted voltage recordings. Therefore, we built a model that was verified by small axonal recordings. The model accurately recreated actual action potential measurements with typical recording artefacts and predicted the native electrical behavior. The simulations verified that recording instruments substantially filter voltage recordings. Moreover, we revealed that instrumentation directly interferes with local signal generation depending on the size of the recorded structures, which complicates the interpretation of recordings from smaller structures, such as axons. However, our model offers a straightforward approach that predicts the native waveforms of fast voltage signals and the underlying conductances even from the smallest neuronal structures.

neuroscience↗