Biology subjects

Golshani, P.

Publications and source records attributed to Golshani, P..

At least 19 recordsLinked to original sources

bioRxiv2026

Attentional modulation of persistent visual representations after stimulus offset is coordinated across primary visual and anterior cingulate cortices

Flexible behavior in complex environments requires animals to infer which sensory inputs are relevant for guiding action and which need to be ignored. Yet, how cognitive control circuits apply contextual knowledge during decision-making is poorly understood. To address this question, we trained head-fixed mice on a cross-modal, context-dependent two-alternative forced-choice (2-AFC) decision-making task. In this task, animals simultaneously received visual and auditory inputs, and the behaviorally relevant modality switched covertly between blocks of trials, requiring animals to infer rule changes from reward feedback alone. Mice successfully adapted their behavior after rule switches and recovered to expert performance. Using simultaneous Neuropixels recordings in the primary visual cortex (V1) and the anterior cingulate cortex (ACC) during task performance, we found that neuronal responses in both regions showed mixed selectivity, multiplexing sensory, choice, and outcome signals. However, V1 neural responses more strongly encoded visual stimulus orientation, while ACC neural responses preferentially encoded outcome. Population decoding further revealed that V1 and ACC neurons maintained a persistent representation of task context throughout the trial, occupying a subspace approximately orthogonal to visual stimulus coding. This contextual representation strengthened progressively as mice adapted their behavior following each switch. Critically, context representations emerged in parallel in V1 and ACC, and decoding accuracies in these two regions were strongly correlated with each other and with behavioral performance across trial blocks. Orthogonal to this shared emergent and sustained context signal, visual stimulus decoding was enhanced when vision was task-relevant. This attentional enhancement in V1 occurred not only during the stimulus presentation period but also after stimulus offset. Similarly, in ACC, a persistent increase of visual stimulus identity encoding in visually relevant session blocks was present after stimulus offset. Taken together, these findings reveal a distributed, inter-areal representation of task context spanning sensory and frontal cortices, suggesting that V1 and ACC contribute to maintaining task-relevant sensory information beyond the immediate sensory response period to provide a circuit-level mechanism for cross-modal attentional control.

neuroscience↗

bioRxiv2026

Miniscope Zero: a fully wireless, single-cell-resolution miniature microscope for imaging neural dynamics in freely behaving animals

Imaging neural fluorescence dynamics during unconstrained behavior remains a major challenge in neuroscience. Head-mounted miniature one-photon microscopes enable in vivo recordings from freely behaving animals. Still, their power and data requirements typically necessitate tethers or heavy batteries, which constrain experiments and may introduce behavioral artifacts. We present Miniscope Zero, a fully wireless miniature microscope platform combining quasistatic cavity resonance (QSCR) wireless power transfer with a high-bandwidth optical data link. The system delivers >500 mW of receiver power across a 2,500 cm2 behavioral arena and streams imaging data at 8 Mbps, supporting real-time data acquisition. Miniscope Zero provides a typical field of view of 600 m x 600 m and a 2.6-fold higher light-collection efficiency than the UCLA Miniscope v4. We demonstrate wireless CA1 GCaMP6f recordings during open-field navigation, enclosed-maze exploration, simultaneous multi-animal imaging, and extended three-dimensional behavior, enabling long-duration cellular-resolution imaging without tether-induced constraints.

neuroscience↗

bioRxiv2026

NMDA receptor-dependent Hebbian plasticity refines hippocampal spatial representations during two-dimensional navigation learning

Hippocampal place cell activity represents an animals location in space; yet, how hippocampal neuronal population dynamics change with spatial learning and the mechanisms underlying these activity changes, which drive allocentric navigation to a learned goal, are poorly understood. To address these questions, we performed calcium imaging with a novel wire-free waterproof miniaturized microscope to image the activity of large populations of hippocampal CA1 neurons during spatial learning of a two-dimensional navigational task, the Morris water maze. We followed the same cells during learning and were able to directly examine how each neuron in the ensemble, and the ensemble as a whole, changes its response properties. We found that neuronal spatial selectivity increased and population decoding of spatial location improved as mice learned to navigate to the goal. Viral CRISPR knock out of Grin1 (encoding the essential GluN1 NMDA receptor subunit) in dorsal hippocampal neurons, dramatically reduced long-term potentiation in CA1. This manipulation also prevented the increase in spatial selectivity and improvement of population decoding with spatial learning and resulted in learning deficits in the Morris water maze. Together, our results show that dorsal hippocampus NMDAR-dependent synaptic plasticity is essential for the learning-dependent refinement of CA1 place selectivity and improvement in population decoding of space.

neuroscience↗

bioRxiv2026

STIMscope: centimeter-scale all-optical imaging and patterned optogenetic manipulation at single-cell resolution

Linking observation to intervention at cellular resolution makes it possible to move from measuring network activity to testing the contribution of defined neurons or ensembles within the same preparation. All-optical probing provides this capability by combining fluorescence-based readout with targeted optogenetic manipulation. Yet the platforms that deliver this capability remain complex, expensive, and difficult to maintain, requiring specialized expertise that has confined them to a small number of laboratories. They also typically provide fields of view too limited for studies of large, distributed neuronal populations. We address these constraints with the Spatiotemporal Illumination Microscope (STIMscope), a one-photon benchtop platform that integrates large-aperture tandem optics with a small-pixel back-illuminated CMOS sensor, a digital micromirror device for patterned illumination, and a GPU-based processing unit coordinated by a microcontroller for hardware-level synchronization. Ray-tracing simulations and point-spread-function measurements confirm cellular-scale resolution, with imaging lateral FWHM of 5.6 {micro}m at the field center and 5.8 {micro}m at the edge, and excitation lateral FWHM of 5.8 {micro}m at the center and 6.2 {micro}m at the edge, supporting fields of view as large as 14 mm x 11 mm in the demagnified configuration. The accompanying Closed-loop ready Real-time Imaging and Stimulation Pipeline (CRISPI) provides GPU-accelerated calibrated mask projection (26.3 ms latency), online ROI trace extraction, and modular ZeroMQ-based control, with a measured imaging-to-stimulation loop benchmark of 91.6 ms. We validate STIMscope in fixed mouse brain tissue, live iPSC-derived human neuronal cultures, and ex vivo organotypic slices of mouse auditory cortex. In organotypic slices, we show that both static and spatiotemporal stimulus identity can be decoded from population activity, revealing reservoir-like population dynamics, and that this decodability remains stable in the same neuronal population over hours. We further show that post-stimulus activity retains information about recent stimuli for several seconds, consistent with short-term memory dynamics. With a bill of materials under $5,000 USD and all mechanical designs, firmware, and software released open-source, STIMscope makes all-optical neuroscience experiments a routine capability accessible to laboratories without specialized optical engineering expertise.

bioengineering↗

bioRxiv2026

Single-Nucleus Transcriptomics Reveals Cell Type-Specific Remodeling and Epilepsy-Associated Microglia

Mesial temporal lobe epilepsy (TLE) is the most common form of acquired epilepsy involving the hippocampus and is a frequent sequelae of head trauma. TLE is associated with refractory seizures and significant cognitive deficits. Yet, the gene expression patterns and cell types driving epileptogenesis and the associated cognitive deficits are poorly understood. To address this, we performed single nucleus RNA sequencing on hippocampal tissue from mice at 3 and 6 weeks following pilocarpine-induced status epilepticus, a robust model of TLE. At these early timepoints, epilepsy samples showed reductions in specific Cck and Lamp5-Lhx6 interneuron subclusters, alongside increases in Cajal-Retzius cells, dentate granule (DG) cell precursors, and a mature DG cell subcluster. Among glia, an astrocyte subcluster and a markedly expanded microglia sublcuster were increased. We term this microglia population epilepsy-associated microglia (EAM). The transcriptomic profile of EAM partially overlaps with microglia described in models of Alzheimers disease and traumatic brain injury, with enrichment of genes including Myo1e and Igf1. EAM display amoeboid morphology, can be found in dense clumps around pyramidal and granule cell body layers, and exhibit enlarged vesicles and mitochondria on electron microscopy. Cell-cell interaction analysis predict that DG cells are the main interaction partners of EAM. This dataset recapitulates known cellular alterations in TLE while defining their underlying transcriptomic programs, enabling mechanistic dissection of the key processes driving epileptogenesis.

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.

neuroscience↗

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.

neuroscience↗

bioRxiv2024

MiniXL: An open-source, large field-of-view epifluorescence miniature microscope for mice capable of single-cell resolution and multi-brain region imaging

Capturing the intricate dynamics of neural activity in freely behaving animals is essential for understanding the neural mechanisms underpinning specific behaviors. Miniaturized microscopy enables investigators to track population activity at cellular level, but the field of view (FOV) of these microscopes have been limited and does not allow multiple-brain region imaging. To fill this technological gap, we have developed the eXtra Large field-of-view Miniscope (MiniXL), a 3.5g lightweight miniaturized microscope with an FOV measuring 3.5 mm in diameter and an electrically adjustable working distance of 1.9 mm {+/-} 200 m. We demonstrated the capability of MiniXL recording the activity of large neuronal population in both subcortical area (hippocampal dorsal CA1) and deep brain regions (medial prefrontal cortex, mPFC and nucleus accumbens, NAc). The large FOV allows simultaneous imaging of multiple brain regions such as bilateral mPFCs or mPFC and NAc during complex social behavior and tracking cells across multiple sessions. As with all microscopes in the UCLA Miniscope ecosystem, the MiniXL is fully open-source and will be shared with the neuroscience community to lower the barriers for adoption of this technology.

neuroscience↗

bioRxiv2024

Open-source, high performance miniature multiphoton microscopy systems for freely behaving animals

Here we describe the development of the UCLA 2P Miniscope, an easily adopted, open-source miniature 2-photon microscope capable of recording calcium dynamics from neurons located in deep structures and in dendrites over a 445 m x 380 m field of view (FOV) during free behavior. The system weighs approximately 4g and utilizes two on-board silicon-based photon detectors for highly sensitive measurements. All hardware is designed for high performance and ease of assembly, while minimizing cost. To test the 2P miniature microscope, we recorded in three experimental conditions to highlight its capabilities during free behavior in mice. First, we recorded calcium dynamics from place cells in hippocampal area CA1. Next, we resolved calcium transients from dendrites in retrosplenial cortex during 30 minutes of free behavior. Last, we recorded dentate granule cell activity at a depth of over 620 m, through an intact hippocampal CA1 during an open field behavior. The dentate granule cell recordings, to our knowledge, are the first optical recordings from these neurons ever performed in the intact hippocampus during free behavior. The miniature microscope itself and all supporting equipment are open-source and all files needed for building the scope can be accessed through the UCLA Golshani Lab GitHub repository.

neuroscience↗

bioRxiv2023

Shifts in attention drive context-dependent subspace encoding in anterior cingulate cortex during decision making

Attention is a cognitive faculty that selects part of a larger set of percepts, driven by cues such as stimulus saliency, internal goals or priors. The enhancement of the attended representation and inhibition of distractors have been proposed as potential neural mechanisms driving this selection process. Yet, how attention operates when the cue has to be internally constructed from conflicting stimuli, decision rules, and reward contingencies, is less understood. Here we recorded from populations of neurons in the anterior cingulate cortex (ACC), an area implicated in ongoing error monitoring and correction during decision conflicts, in a challenging attention-shifting task. In this task, mice had to attend to the rewarded modality when presented identical auditory and visual stimuli in two contexts without direct external cues. In the ACC, the irrelevant stimulus continuously became less decodable than the relevant stimulus as the trial progressed to the decision point. This contrasted strongly with our previous findings in V1 where both relevant and irrelevant stimuli were equally decodable throughout the trial. Using analytical tools and a recurrent neural network (RNN) model, we found that the linearly independent representation of stimulus modalities in ACC was well suited to context-gated suppression of a stimulus modality. We demonstrated that the feedback structure of lateral connections in the RNN consisted of excitatory interactions between cell ensembles representing the same modality and mutual inhibition between cell ensembles representing distinct stimulus modalities. Using this RNN model showing signatures of context-gated suppression, we predicted that the level of contextual modulation of individual neurons should be correlated with their relative responsiveness to the two stimulus modalities used in the task. We verified this prediction in recordings from ACC neurons but not from recordings from V1 neurons. Therefore, ACC effectively operates on low-dimensional neuronal subspaces to combine stimulus related information with internal cues to drive actions under conflict.

neuroscience↗

bioRxiv2023

Accelerated social representational drift in the nucleus accumbens in a model of autism

Impaired social interaction is one of the core deficits of autism spectrum disorder (ASD) and may result from social interactions being less rewarding. How the nucleus accumbens (NAc), as a key hub of reward circuitry, encodes social interaction and whether these representations are altered in ASD remain poorly understood. We identified NAc ensembles encoding social interactions by calcium imaging using miniaturized microscopy. NAc population activity, specifically D1 receptor-expressing medium spiny neurons (D1-MSNs) activity, predicted social interaction epochs. Despite a high turnover of NAc neurons modulated by social interaction, we found a stable population code for social interaction in NAc which was dramatically degraded in Cntnap2-/- mouse model of ASD. Surprisingly, non-specific optogenetic inhibition of NAc core neurons increased social interaction time and significantly improved sociability in Cntnap2-/- mice. Inhibition of D1- or D2-MSNs showed reciprocal effects, with D1 inhibition decreasing social interaction and D2 inhibition increasing interaction. Therefore, social interactions are preferentially, specifically and dynamically encoded by NAc neurons and social representations are degraded in this autism model.

neuroscience↗

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.

neuroscience↗

bioRxiv2023

Correlated signatures of social behavior in cerebellum and anterior cingulate cortex

The cerebellum has been implicated in the regulation of social behavior. Its influence is thought to arise from communication, via the thalamus, to forebrain regions integral in the expression of social interactions, including the anterior cingulate cortex (ACC). However, the signals encoded or the nature of the communication between the cerebellum and these brain regions is poorly understood. Here, we describe an approach that overcomes technical challenges in exploring the coordination of distant brain regions at high temporal and spatial resolution during social behavior. We developed the E-Scope, an electrophysiology-integrated miniature microscope, to synchronously measure extracellular electrical activity in the cerebellum along with calcium imaging of the ACC. This single coaxial cable device combined these data streams to provide a powerful tool to monitor the activity of distant brain regions in freely behaving animals. During social behavior, we recorded the spike timing of multiple single units in cerebellar right Crus I (RCrus I) Purkinje cells (PCs) or dentate nucleus (DN) neurons while synchronously imaging calcium transients in contralateral ACC neurons. We found that during social interactions a significant subpopulation of cerebellar PCs were robustly inhibited, while most modulated neurons in the DN were activated, and their activity was correlated with positively modulated ACC neurons. These distinctions largely disappeared when only non-social epochs were analyzed suggesting that cerebellar-cortical interactions were behaviorally specific. Our work provides new insights into the complexity of cerebellar activation and co-modulation of the ACC during social behavior and a valuable open-source tool for simultaneous, multimodal recordings in freely behaving mice.

neuroscience↗

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.

neuroscience↗

bioRxiv2022

Disruption of place cell remapping by scopolamine during aversive learning

Aversive stimuli can cause hippocampal place cells to remap their firing fields, but it is not known whether remapping plays a role in storing memories of aversive experiences. Here we addressed this question by performing in-vivo calcium imaging of CA1 place cells in freely behaving rats (n=14). Rats were first trained to prefer a short path over a long path for obtaining food reward, then trained to avoid the short path by delivering a mild footshock. Remapping was assessed by comparing place cell population vector similarity before acquisition versus after extinction of avoidance. Some rats received shock after systemic injections of the amnestic drug scopolamine at a dose (1 mg/kg) that impaired avoidance learning but spared spatial tuning and shock-evoked responses of CA1 neurons. Place cells remapped significantly more following remembered than forgotten shocks (drug-free versus scopolamine conditions); shock-induced remapping did not cause place fields to migrate toward or away from the shocked location and was similarly prevalent in cells that were responsive versus non-responsive to shocks. When rats were exposed to a neutral barrier rather than aversive shock, place cells remapped significantly less in response to the barrier. We conclude that place cell remapping occurs in response to events that are remembered rather than merely perceived and forgotten, suggesting that reorganization of hippocampal population codes may play a role in storing memories for aversive events.

neuroscience↗

bioRxiv2022

A hardware system for real-time decoding of in-vivo calcium imaging data

Epifluorescence miniature microscopes ("miniscopes") are widely used for in vivo calcium imaging of neural population activity. Imaging data is usually collected while subjects are engaged in a task and stored for later offline analysis, but emerging techniques for online imaging offer potential for novel real-time experiments in which closed-loop interventions (such as neurostimulation or sensory feedback) are triggered at short latencies in response to neural population activity. Here we introduce DeCalciOn, a plug-and-play hardware device for online population decoding of in vivo calcium signals that can trigger closed-loop feedback at millisecond latencies, and is compatible with miniscopes that use the UCLA Data Acquisition (DAQ) interface. In performance tests, the position of rats (n=13) on a linear track was decoded in real time from hippocampal CA1 population activity by 24 linear classifiers. DeCalciOn required <2.5 ms after each end-of-frame to decode up to 1,024 calcium traces and trigger TTL control outputs. Decoding was most efficient using a contour-free method of extracting traces from ROIs that were unaligned with neurons in the image, but contour-based extraction from neuronal ROIs is also supported. DeCalciOn is an easy-to-use system for real-time decoding of calcium fluorescence that enables closed-loop feedback experiments in behaving animals.

neuroscience↗

bioRxiv2021

Miniscope-LFOV: A large field of view, single cell resolution, miniature microscope for wired and wire-free imaging of neural dynamics in freely behaving animals

Imaging large-population, single-cell fluorescent dynamics in freely behaving animals larger than mice remains a key endeavor of neuroscience. We present a large field of view open-source miniature microscope (MiniLFOV) designed for large-scale (3.6 x 2.7 mm), single cell resolution neural imaging in freely behaving rats. It has an electrically adjustable working distance of up to 3.5 mm{+/-}100 m, incorporates an absolute head-orientation sensor, and weighs only 13.9 grams. The MiniLFOV is capable of both deep brain and cortical imaging and has been validated in freely behaving rats by simultaneously imaging >1000 GCaMP7s expressing neurons in the hippocampal CA1 layer and in head-fixed mice by simultaneously imaging ~2000 neurons in the dorsal cortex through a cranial window. The MiniLFOV also supports optional wire-free operation using a novel, wire-free data acquisition expansion board. We expect this new open-source implementation of the UCLA Miniscope platform will enable researchers to address novel hypotheses concerning brain function in freely behaving animals.

neuroscience↗

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↗