Biology subjects

Taxidis, J.

Publications and source records attributed to Taxidis, J..

10 recordsLinked to original sources

bioRxiv2026

Time Cells in the Human Brain Support Working Memory Maintenance

Working memory (WM), the active retention of information over short periods, is a fundamental cognitive function, yet its underlying neural mechanisms remain unclear. In rodents, cue-selective "time cells" fire at specific timepoints after a WM memory cue, collectively forming sequences that encode cue-memory and elapsed time, providing a temporal code for maintaining information across time intervals. Whether similar dynamics support WM in the human brain is unknown. Here, we analyzed intracranial single-neuron recordings from medial frontal and medial temporal regions of patients performing a WM task. We found time cells with temporally tuned activation during WM maintenance, collectively forming robust sequences that tiled a delay period. Time-cell coordination in the hippocampus predicted successful WM maintenance, whereas in the pre-supplementary motor area it reflected memory load. Furthermore, we identified distributed cue-selective time cells that encoded both the identity of a memorandum and elapsed maintenance time, providing a temporally structured mnemonic code that complements persistent firing of concept cells. Together, these findings establish time-cell sequences as a conserved neural mechanism supporting human working memory.

neuroscience↗

bioRxiv2025

Hippocampal sequences represent working memory and implicit timing

Working memory (WM) and timing are considered distinct cognitive functions, yet the neural signatures underlying both can be similar. To address the hypothesis that WM and timing may be multiplexed we developed a novel rodent task where 1st odor identity predicts the delay duration. We found that WM performance decreased when delay expectations were violated. Performance was worse for unexpected long delays than for unexpected short delays, suggesting that WM may be tuned to expire in a delay-dependent manner. Calcium imaging of dorsal CA1 neurons revealed odor-specific sequential activity tiling the short and long delays. Neural sequence structure also reflected expectation of the timing of the 2nd odor--i.e., of the expected delay. Consistent with the hypothesis that WM and timing may be multiplexed, our findings suggest that neural sequences in dorsal CA1 may encode cues and cue-specific elapsed time during the delay period of a WM task.

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bioRxiv2024

Non-spatial hippocampal behavioral timescale synaptic plasticity during working memory is gated by entorhinal inputs

Behavioral timescale synaptic plasticity (BTSP) is a form of synaptic potentiation where a single plateau potential in hippocampal neurons forms a place field during spatial learning. We asked whether BTSP can also form non-spatial responses in the hippocampus and what roles the medial and lateral entorhinal cortex (MEC and LEC) play in driving non-spatial BTSP. Two-photon calcium imaging of dorsal CA1 neurons while mice performed an odor-cued working memory task revealed plateau-like events which formed stable odor-specific responses. These BTSP-like events were much more frequent during the first day of task learning, suggesting that BTSP may be important for early learning. Strong single-neuron stimulation through holographic optogenetics induced plateau-like events and subsequent odor-fields, causally linking BTSP with non-spatial representations. MEC chemogenetic inhibition reduced the frequency of plateau-like events, whereas LEC inhibition reduced potentiation and field-induction probability. Calcium imaging of LEC and MEC temporammonic CA1 projections revealed that MEC axons were more strongly activated by odor presentations, while LEC axons were more odor-selective, further confirming the role of MEC in driving plateau-like events and LEC in relaying odor-specific information. Altogether, odor-specific information from LEC and strong odor-timed activity from MEC are crucial for driving BTSP in CA1, which is a synaptic plasticity mechanism for generation of both spatial and non-spatial responses in the hippocampus.

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bioRxiv2023

Voltage imaging reveals that hippocampal interneurons tune memory-encoding pyramidal sequences

Hippocampal spiking sequences encode and link behavioral information across time. How inhibition sculpts these sequences remains unknown. We performed longitudinal voltage imaging of CA1 parvalbumin- and somatostatin-expressing interneurons in mice during an odor-cued working memory task, before and after training. During this task, pyramidal odor-specific sequences encode the cue throughout a delay period. In contrast, most interneurons encoded odor delivery, but not odor identity, nor delay time. Population inhibition was stable across days, with constant field turnover, though some cells retained odor-responses for days. At odor onset, a brief, synchronous burst of parvalbumin cells was followed by widespread membrane hyperpolarization and then rebound theta-paced spiking, synchronized across cells. Two-photon calcium imaging revealed that most pyramidal cells were suppressed throughout the odor. Positive pyramidal odor-responses coincided with interneuronal rebound spiking; otherwise, they had weak odor-selectivity. Therefore, inhibition increases the signal-to-noise ratio of cue representations, which is crucial for entraining downstream targets.

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bioRxiv2022

Multiplexing working memory and time: encoding retrospective and prospective information in neural trajectories

Working memory (WM) and timing are generally considered distinct cognitive functions, but similar neural signatures have been implicated in both. To explore the hypothesis that WM and timing may rely on shared neural mechanisms, we used psychophysical tasks that contained either task-irrelevant timing or WM components. In both cases the task-irrelevant component influenced performance. RNN simulations revealed that cue-specific neural sequences, which multiplexed WM and time, emerged as the dominant regime that captured the behavioral findings. Over the course of training RNN dynamics transitioned from low-dimensional ramps to high-dimensional neural sequences, and depending on task requirements, steady-state or ramping activity was also observed. Analysis of RNN structure revealed that neural sequences relied primarily on inhibitory connections, and could survive the deletion of all excitatory-to- excitatory connections. Our results suggest that in some instances WM is encoded in time-varying neural activity because of the importance of predicting when WM will be used.

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bioRxiv2021

A positively Tuned Voltage Indicator Reveals Electrical Correlates of Calcium Activity in the Brain

Neuronal spiking activity is routinely recorded using genetically encoded calcium indicators (GECIs), but calcium imaging is limited in temporal resolution and does not report subthreshold voltage changes. Genetically encoded voltage indicators (GEVIs) offer better temporal resolution and subthreshold sensitivity, but spike detection with fast GEVIs has required specialized imaging equipment. Here, we report the ASAP4 subfamily of genetically encoded voltage indicators (GEVIs) that brighten in response to membrane depolarization, inverting the fluorescence-voltage relationship of previous ASAP GEVIs. Two variants, ASAP4b and ASAP4e, feature 128% and 178% fluorescence increases over 100-mV of depolarization, respectively, facilitating spike detection in single trials in vivo with standard 1 and 2-photon imaging systems. Simultaneous voltage and calcium imaging confirms improved temporal resolution and spike discernment by ASAP4 GEVIs. Thus, positively tuned ASAP4 voltage indicators enable recording of neuronal spiking activity using similar equipment as calcium imaging, while providing higher temporal resolution. One Sentence SummaryUpward ASAPs increase detection capability of GEVIs in vivo.

neuroscience↗

bioRxiv2018

Emergence of stable sensory and dynamic temporal representations in the hippocampus during working memory

Hippocampal networks form maps of experience through spiking sequences that encode sensory cues, space or time. But whether distinct rules govern the emergence, stability and plasticity of externally driven and internally-generated representations remains unclear. Using two-photon calcium imaging, we recorded CA1 pyramidal populations across multiple days, while mice learned and performed an olfactory, delayed, working-memory task. We observed anatomically intermixed spiking sequences, comprised of odor-cells encoding olfactory cues, followed by time-cells encoding odor-specific delay time-points. Odor-cells were reliably activated across trials and retained stable fields over days and different delays. In contrast, time-cells exhibited sparse, unreliable activation and labile fields that remapped over days and extended delays. Moreover, the number of odor-cells remained stable, whereas time-cells increased over days during learning of the task, but not during passive exposure. Therefore, multi-modal representations with distinct learning-related dynamics and stability can co-exist in CA1, likely driven by different neurophysiological and plasticity mechanisms.

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bioRxiv2018

Breakdown of spatial coding and neural synchronization in epilepsy

Temporal lobe epilepsy causes significant cognitive deficits in both human patients and rodent models, yet the specific circuit mechanisms that alter cognitive processes remain unknown. There is dramatic and selective interneuron death and axonal reorganization within the hippocampus of both humans and animal models, but the functional consequences of these changes on information processing at the neuronal population level have not been well characterized. To examine spatial representations of epileptic and control mice, we developed a novel wire-free miniature microscope to allow for unconstrained behavior during in vivo calcium imaging of neuronal activity. We found that epileptic mice running on a linear track had severely impaired spatial processing in CA1 within a single session, as place cells were less precise and less stable, and population coding was impaired. Long-term stability of place cells was also compromised as place cells in epileptic mice were highly unstable across short time intervals and completely remapped across a week. Because of the large-scale reorganization of inhibitory circuits in epilepsy, we hypothesized that degraded spatial representations were caused by dysfunctional inhibition. To test this hypothesis, we examined the temporal dynamics of hippocampal interneurons using silicon probes to simultaneously record from CA1 and dentate gyrus during head-fixed virtual navigation. We found that epileptic mice had a profound reduction in theta coherence between the dentate gyrus and CA1 regions and altered interneuron synchronization. In particular, dentate interneurons of epileptic mice had altered phase preferences to ongoing theta oscillations, which decorrelated inhibitory population firing between CA1 and dentate gyrus. To assess the specific contribution of desynchronization on spatial coding, we built a CA1 network model to simulate hippocampal desynchronization. Critically, we found that desynchronized inputs reduced the information content and stability of CA1 neurons, consistent with the experimental data. Together, these results demonstrate that temporally precise intra-hippocampal communication is critical for forming the spatial code and that desynchronized firing of hippocampal neuronal populations contributes to poor spatial processing in epileptic mice.

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bioRxiv2018

CaImAn: An open source tool for scalable Calcium Imaging data Analysis

Advances in fluorescence microscopy enable monitoring larger brain areas in-vivo with finer time resolution. The resulting data rates require reproducible analysis pipelines that are reliable, fully automated, and scalable to datasets generated over the course of months. Here we present CaImAn, an open-source library for calcium imaging data analysis. CaImAn provides automatic and scalable methods to address problems common to pre-processing, including motion correction, neural activity identification, and registration across different sessions of data collection. It does this while requiring minimal user intervention, with good performance on computers ranging from laptops to high-performance computing clusters. CaImAn is suitable for two-photon and one-photon imaging, and also enables real-time analysis on streaming data. To benchmark the performance of CaImAn we collected a corpus of ground truth annotations from multiple labelers on nine mouse two-photon datasets. We demonstrate that CaImAn achieves near-human performance in detecting locations of active neurons.

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bioRxiv2018

Reduced prefrontal synaptic connectivity and disturbed oscillatory population dynamics in the CNTNAP2 model of autism

Loss of function mutations in CNTNAP2 cause a syndromic form of autism spectrum disorder (ASD) in humans and produce social deficits, repetitive behaviors, and seizures in mice. Yet, the functional effects of these mutations at the cellular and circuit level remain elusive. Using laser scanning photostimulation, whole-cell recordings, and electron microscopy, we found a dramatic decrease in functional excitatory and inhibitory synaptic inputs in L2/3 medial prefrontal cortex (mPFC) of Cntnap2 knock-out (KO) mice. In accordance with decreased synaptic input, KO mice displayed reduced spine and synapse densities, despite normal intrinsic excitability, as well as reduced short term plasticity, and dendritic complexity. To determine how this decrease in synaptic inputs alters coordination of neuronal firing patterns in vivo, we recorded mPFC local field potentials (LFP) and unit spiking in head-fixed mice during locomotion and rest. In KO mice, LFP power was not significantly altered at all tested frequencies, but inhibitory neurons showed delayed phase-firing and reduced phase-locking to delta and theta oscillations during locomotion. Excitatory neurons showed similar changes but only to delta oscillations. These findings suggest that profound ASD-related alterations in synaptic inputs can yield perturbed temporal coordination of cortical ensembles.

neuroscience↗