Biology subjects

Jadhav, S. P.

Publications and source records attributed to Jadhav, S. P..

16 recordsLinked to original sources

bioRxiv2025

Cooperative behavior guided by peer coordination is impaired in a Fragile-X rat model of autism

Cooperative behavior, the ability of individuals to coordinate their actions toward shared goals, is fundamental to survival and social success across species. However, the mechanisms supporting cooperation and how their disruption leads to social deficits in neurodevelopmental disorders such as autism spectrum disorder (ASD), remain poorly understood. To address these questions, we developed a novel cooperation task in paired spatial mazes under deterministic (100%) and probabilistic (50%) reward contingencies, utilizing dyads of littermate wild-type (WT) and Fmr1 knockout (Fmr1) rats, a model of Fragile X syndrome. Both WT and Fmr1 rat pairs exhibited dynamic turn-taking with mixed leader-follower behavior for cooperation; however, WT pairs achieved significantly greater cooperation success than Fmr1 pairs. WT and Fmr1 pairs both successfully utilized a simple follower-tracking-leader reactive strategy, dependent on partner-directed visual attention, resulting in slower asynchronous transitions, with Fmr1 pairs more reliant on this strategy. WT rat pairs in addition exhibited a more efficient, flexible predictive cooperation strategy, dependent on coordination of optimal transition patterns between rat pairs and recent partner choice history, resulting in faster synchronous transitions. Fmr1 rats were unable to show adaptation to the probabilistic reward condition by employing this more efficient social reciprocity strategy of higher complexity, leading to deficits in cooperative behavior. These findings reveal key behavioral strategies of varying complexity for cooperation, reveal the specific disruption of complex social reciprocity strategies in a rat ASD model, and provide a foundation for investigation of social interactions and underlying neural mechanisms in cooperative decision-making with relevance to neurodevelopmental disorders.

neuroscience↗

bioRxiv2025

REM sleep prefrontal ripple chains mediate distinct cortical-hippocampal reactivation patterns compared to NREM ripples

REM (rapid eye movement) and non-REM (NREM) sleep stages contribute to systems memory consolidation in hippocampal-cortical circuits. However, the physiological mechanisms underlying REM memory processes remain relatively unclear compared to NREM memory reactivation. Here we report, in rodents, the existence of prefrontal cortical (PFC) high-frequency oscillation (HFO) chains in REM sleep during consolidation of recently acquired spatial memory. High-density tetrode recordings in hippocampal area CA1 and PFC reveal that REM cortical HFOs occur in characteristic chains that are phase modulated by theta oscillations, corresponding to increased CA1-PFC theta coherence and delineating periods of enhanced hippocampal-cortical communication. REM HFO chains sequentially organize sparse PFC ensemble reactivation of behavioral activity during periods of local suppression, distinct from widespread reactivation bursts during NREM ripple oscillations. REM HFO chains also preferentially engage CA1 neuronal populations that demonstrate a shift in their preferred theta-phase from behavior to REM sleep. CA1 neuronal activation during REM HFO chains was correlated with CA1 activity suppression during NREM PFC ripples, and linked to differential changes in CA1 firing rates in sleep, suggesting REM-driven regulation of hippocampal excitability. A cortical network model incorporating the effects of acetylcholine can reproduce the distinct REM and NREM activity patterns, providing a mechanistic basis for widespread coactivity during NREM cortical ripples, compared to sparse, temporally extended reactivation on a background of local suppression during REM HFO chains. Overall, these findings establish a role for PFC high-frequency oscillations in regulating distinct dual sleep stage reactivation patterns.

neuroscience↗

bioRxiv2025

A novel rat spatial transitive inference paradigm for investigating memory schema and deliberation

Inferential reasoning is a vital cognitive ability that enables animals to navigate novel situations by leveraging existing relational knowledge of memory schema, with hypothesized roles of prefrontal cortical - hippocampal circuits. Transitive inference (TI) tasks test the ability of subjects to infer relationships within a value hierarchy (e.g., A>B>C>D>E) after being trained only on adjacent premise pairs (e.g., A-B, B-C, etc.). In rodents, current TI paradigms are primarily based on odor-cues and have several limitations that preclude investigation of physiological mechanisms underlying schemas and deliberation. To address these challenges, we developed a novel, automated spatial TI task for rats using a radial maze with maze arms as premise elements and a dedicated deliberation zone. Most rats successfully learned the premise pairs over training. Further, animals demonstrated rapid, successful inference (test pair B>D and control pair A>E) within a single test session, with higher initial accuracy than comparable premise pairs, indicating the use of schema-based inference. We also investigated vicarious trial and errors (VTE), a behavioral correlate of spatial deliberation. VTE behavior was elevated on choice trajectories early in learning, when novel premise pairs were introduced, and generally for incorrect trials, corresponding to the hypothesized association of VTEs with uncertainty. Further, rats also exhibited elevated VTE behavior with high variability during inference testing, with individual variability suggestive of varying strengths of schema usage. Our findings demonstrate the feasibility of a rodent spatial TI task that provides new insights into the behavioral correlates of schemas and deliberation for inferential reasoning.

animal behavior and cognition↗

bioRxiv2024

Ventral tegmental area dopamine neural activity switches simultaneously with rule representations in the prefrontal cortex and hippocampus

Multiple brain regions need to coordinate activity to support cognitive flexibility and behavioral adaptation. Neural activity in both the hippocampus (HPC) and prefrontal cortex (PFC) is known to represent spatial context and is sensitive to reward and rule alterations. Midbrain dopamine (DA) activity is key in reward seeking behavior and learning. There is abundant evidence that midbrain DA modulates HPC and PFC activity. However, it remains underexplored how these networks engage dynamically and coordinate temporally when animals must adjust their behavior according to changing reward contingencies. In particular, is there any relationship between DA reward prediction change during rule switching, and rule representation changes in PFC and CA1? We addressed these questions using simultaneous recording of neuronal population activity from the hippocampal area CA1, PFC and ventral tegmental area (VTA) in male TH-Cre rats performing two spatial working memory tasks with frequent rule switches in blocks of trials. CA1 and PFC ensembles showed rule-specific activity both during maze running and at reward locations, with PFC rule coding more consistent across animals compared to CA1. Optogenetically tagged VTA DA neuron firing activity responded to and predicted reward outcome. We found that the correct prediction in DA emerged gradually over trials after rule-switching in coordination with transitions in PFC and CA1 ensemble representations of the current rule after a rule switch, followed by behavioral adaptation to the correct rule sequence. Therefore, our study demonstrates a crucial temporal coordination between the rule representation in PFC/CA1, the dopamine reward signal and behavioral strategy. Significance StatementThis study examines neural activity in mammalian brain networks that support the ability to respond flexibly to changing contexts. We use a rule-switching spatial task to examine whether the key reward-responsive and predictive dopamine (DA) activity changes in coordination with changes in rule representations in key cognitive regions, the prefrontal cortex (PFC) and hippocampus. We first established distinct rule representations in PFC and hippocampus, and predictive coding of reward outcomes by DA neuronal activity. We show that the rule-specific DA reward prediction after a rule switch develops in temporal coordination with changes in rule representations in PFC, eventually leading to behavioral changes. These results thus provide an integrated understanding of reward prediction, cognitive representations of rules and behavioral adaptation.

neuroscience↗

bioRxiv2024

Hippocampal-prefrontal communication subspaces align with behavioral and network patterns in a spatial memory task

Rhythmic network states have been theorized to facilitate communication between brain regions, but how these oscillations influence communication subspaces, i.e, the low-dimensional neural activity patterns that mediate inter-regional communication, and in turn how subspaces impact behavior remains unclear. Using a spatial memory task in rats, we simultaneously recorded ensembles from hippocampal CA1 and the prefrontal cortex (PFC) to address this question. We found that task behaviors best aligned with low-dimensional, shared subspaces between these regions, rather than local activity in either region. Critically, both network oscillations and speed modulated the structure and performance of this communication subspace. Contrary to expectations, theta coherence did not better predict CA1-PFC shared activity, while theta power played a more significant role. To understand the communication space, we visualized shared CA1-PFC communication geometry using manifold techniques and found ring-like structures. We hypothesize that these shared activity manifolds are utilized to mediate the task behavior. These findings suggest that memory-guided behaviors are driven by shared CA1-PFC interactions that are dynamically modulated by oscillatory states, offering a novel perspective on the interplay between rhythms and behaviorally relevant neural communication.

neuroscience↗

bioRxiv2023

Cortical ripples mediate top-down suppression of hippocampal reactivation during sleep memory consolidation

Consolidation of initially encoded hippocampal representations in the neocortex through reactivation is crucial for long-term memory formation, and is facilitated by the coordination of hippocampal sharp-wave ripples (SWRs) with cortical oscillations during non-REM sleep. However, the contribution of high-frequency cortical ripples to consolidation is still unclear. We used continuous recordings in the hippocampus and prefrontal cortex (PFC) over the course of spatial learning and show that independent PFC ripples, when dissociated from SWRs, predominantly suppress hippocampal activity in non-REM sleep. PFC ripples paradoxically mediate top-down suppression of hippocampal reactivation, which is inversely related to reactivation strength during coordinated CA1-PFC ripples. Further, we show non-canonical, serial coordination of ripples with cortical slow and spindle oscillations. These results establish a role for cortical ripples in regulating consolidation.

neuroscience↗

bioRxiv2023

Intrinsic dynamics of randomly clustered networks generate place fields and preplay of novel environments

During both sleep and awake immobility, hippocampal place cells reactivate time-compressed versions of sequences representing recently experienced trajectories in a phenomenon known as replay. Intriguingly, spontaneous sequences can also correspond to forthcoming trajectories in novel environments experienced later, in a phenomenon known as preplay. Here, we present a model showing that sequences of spikes correlated with the place fields underlying spatial trajectories in both previously experienced and future novel environments can arise spontaneously in neural circuits with random, clustered connectivity rather than pre-configured spatial maps. Moreover, the realistic place fields themselves arise in the circuit from minimal, landmark-based inputs. We find that preplay quality depends on the networks balance of cluster isolation and overlap, with optimal preplay occurring in small-world regimes of high clustering yet short path lengths. We validate the results of our model by applying the same place field and preplay analyses to previously published rat hippocampal place cell data. Our results show that clustered recurrent connectivity can generate spontaneous preplay and immediate replay of novel environments. These findings support a framework whereby novel sensory experiences become associated with preexisting "pluripotent" internal neural activity patterns.

neuroscience↗

bioRxiv2021

Adaptable and Automated Rodent Behavior Maze System

Mazes are a fundamental and widespread tool in behavior and systems neuroscience research in rodents, especially in spatial navigation and spatial memory investigations in freely behaving animals. However, their form and inflexibility often restrict potential experimental paradigms that involve multiple or adaptive maze designs. Unique layouts often lead to elevated costs, whether financially or in terms of time investment from scientists. To alleviate these issues, we have developed an automated, modular maze system that is flexible and scalable. This open source Adapt-A-Maze (AAM) system will allow for experiments with multiple track configurations in rapid succession. Additionally, the flexibility can expedite prototyping of behavioral paradigms. Automation ensures less variability in experimental parameters and higher throughput. Finally, the standardized componentry enhances experimental repeatability within labs and replicability across labs. Our maze was successfully used across labs, in multiple experimental designs, with and without extracellular or optical recordings, in rats. The AAM system presents multiple advantages over current maze options and can facilitate novel behavior and systems neuroscience research. Significance statementWe have developed an open source, modular maze system (the Adapt-A-Maze, AAM) that enables any lab interested in rodent behavior and cognition to create standard and unique mazes for their research. The AAM uses modular track pieces that can be combined to create a wide array of maze types. The AAM system also included reward wells with lick detection and pneumatic barriers. All aspects of the maze can be controlled via TTL signals to automate tasks and improve repeatability of experiments. The AAM system is expected to help labs quickly and inexpensively set up recordable experiments to advance our understanding of the neurophysiology underlying behavior and cognition.

neuroscience↗

bioRxiv2021

Hippocampal theta sequences in REM sleep during spatial learning

Rapid eye movement (REM) sleep is known to play a role in hippocampally-dependent memory, yet the activity and development of hippocampal neuronal ensembles during this state is not well understood. Here we investigated patterning of CA1 place cell activity by theta oscillations, a shared electrophysiological hallmark of both waking behavior and REM sleep, in male rats learning a spatial memory task. We report the existence of REM theta sequences, sequential reactivations of place cells in REM theta that parallel waking theta sequences. REM and wake theta sequences develop rapidly with experience, recapitulating behavioral sequences of compressed space in forward and reverse directions throughout learning. REM sleep exhibited a balance of forward and reverse sequences in contrast to predominantly forward wake theta sequences. Finally, we found that a CA1 neuronal population known to shift preferred theta phases in REM exhibited differential participation in wake and REM theta sequences. In particular, this phase-shifting population showed an increased contribution to REM theta sequence representations after behavioral performance asymptotes and the task is learned, supporting a previously hypothesized role in depotentiation. These findings suggest a role for REM associated theta sequences in state dependent memory functions of the hippocampal circuit, providing evidence that REM sleep is associated with sequence reactivation that can support consolidation of representations necessary for memory guided behavior.

neuroscience↗

bioRxiv2020

Multiple time-scales of decision making in the hippocampus and prefrontal cortex

The prefrontal cortex and hippocampus are crucial for memory-guided decision-making. Neural activity in the hippocampus exhibits place-cell sequences at multiple timescales, including slow behavioral sequences ([~]seconds) and fast theta sequences ([~]100-200 ms) within theta oscillation cycles. How prefrontal ensembles interact with hippocampal sequences to support decision-making is unclear. Here, we examined simultaneous hippocampal and prefrontal ensemble activity during learning of a spatial working-memory decision task. We found clear theta sequences in prefrontal cortex, nested within its behavioral sequences. In both regions, behavioral sequences maintained representations of current goals during navigation. In contrast, hippocampal theta sequences encoded alternatives for deliberation, and were coordinated with prefrontal theta sequences that predicted upcoming choices. During error trials, these representations were preserved to guide ongoing behavior, whereas replay sequences during inter-trial periods were impaired prior to navigation. These results establish cooperative interaction between hippocampal and prefrontal sequences at multiple timescales for memory-guided decision making.

neuroscience↗

bioRxiv2020

Efficient Spline Regression for Neural Spiking Data

Point process generalized linear models (GLMs) provide a powerful tool for characterizing the coding properties of neural populations. Spline basis functions are often used in point process GLMs, when the relationship between the spiking and driving signals are nonlinear, but common choices for the structure of these spline bases often lead to loss of statistical power and numerical instability when the signals that influence spiking are bounded above or below. In particular, history dependent spike train models often suffer these issues at times immediately following a previous spike. This can make inferences related to refractoriness and bursting activity more challenging. Here, we propose a modified set of spline basis functions that assumes a flat derivative at the endpoints and show that this limits the uncertainty and numerical issues associated with cardinal splines. We illustrate the application of this modified basis to the problem of simultaneously estimating the place field and history dependent properties of a set of neurons from the CA1 region of rat hippocampus, and compare it with the other commonly used basis functions. We have made code available in MATLAB to implement spike train regression using these modified basis functions.

neuroscience↗

bioRxiv2020

Neural coordination mechanisms for associative memory recall and decision making in the hippocampal-prefrontal network

Memory-guided decision making involves long-range coordination across sensory and cognitive brain networks, with key roles for the hippocampus and prefrontal cortex (PFC). To investigate these coordination mechanisms, we monitored activity in hippocampus (CA1), PFC, and olfactory bulb in rats performing an odor-place associative memory guided decision task on a T-maze. During odor sampling, the beta (20-30 Hz) and respiratory (7-8 Hz) rhythms (RR) were prominent across the three regions, with CA1-PFC beta and RR coherence enhanced during the odor-cued decision making period. Beta phase modulation of CA1 and PFC neuronal activity during this period was linked to accurate decisions, suggesting that this temporal modulation influences sensory-cued decision making. Single neurons and ensembles in both CA1 and PFC encoded and predicted animals upcoming choices. Our findings indicate that rhythmic coordination within the hippocampal-prefrontal network supports utilization of odor cues for memory-guided decision making.

neuroscience↗

bioRxiv2019

Reorganization and reactivation of a preexisting taste-responsive hippocampal network

Animals need to remember the locations of nourishing and toxic food sources for survival, a fact that necessitates a mechanism for associating taste experiences with particular places. We have previously identified such responses within hippocampal place cells [1], the activity of which is thought to aid memory-guided behavior by forming a mental map of an animals environment that can be reshaped through experience [2-7]. It remains unknown, however, whether taste-responsiveness is intrinsic to a subset of place cells, or emerges as a result of experience that reorganizes spatial maps. Here, we recorded from neurons in the dorsal CA1 region of rats running for palatable tastes delivered via intra-oral cannulae at specific locations on a linear track. We identified a subset of taste-responsive cells that, even prior to taste exposure, had larger place fields than non-taste-responsive cells overlapping with stimulus delivery zones. Taste-responsive cells place fields then contracted, as a result of taste experience, leading to a stronger representation of stimulus delivery zones on the track. Taste-responsive units exhibited increased sharp-wave ripple co-activation during the taste delivery session and subsequent rest periods, which correlated with the degree of place field contraction. Our results reveal that novel taste experience evokes responses within a preconfigured network of taste-responsive hippocampal place cells with large fields, whose spatial representations are refined by sensory experience to signal areas of behavioral salience. This represents a possible mechanism by which animals identify and remember locations where ecologically relevant stimuli are found within their environment.

neuroscience↗

bioRxiv2019

Awake hippocampal-prefrontal replay mediates spatial learning and decision making

Spatial learning requires remembering and choosing paths to goals. Hippocampal place cells replay spatial paths during immobility in reverse and forward order, offering a potential mechanism. However, how replay mediates both goal-directed learning and memory-guided decision making is unclear. We therefore continuously tracked replay in the same hippocampal-prefrontal ensembles throughout learning of a spatial alternation task. We found that during pauses between behavioral trajectories, awake reverse and forward hippocampal replay consistently mediated an internal cognitive search of all available past and future possibilities, and exhibited opposing learning gradients for prediction of past and future behavioral paths, respectively. Coordinated hippocampal-prefrontal replay mediated recall of correct past paths and selection of future choices leading to reward based on the hippocampal cognitive search, executing spatial working memory rules. Our findings reveal a learning shift from hippocampal reverse-replay-based retrospective evaluation to forward-replay-based prospective planning, with prefrontal filtering of memory-guided paths for learning and decision-making.

neuroscience↗

bioRxiv2019

Coherent coding of spatial position mediated by theta oscillations in hippocampus and prefrontal cortex

Interactions between the hippocampus (area CA1) and prefrontal cortex (PFC) are crucial for memory-guided behavior. Theta oscillations (~8 Hz) underlie a key physiological mechanism for mediating these coordinated interactions, and theta oscillatory coherence and phase-locked spiking in the two regions have been shown to be important for spatial memory. Hippocampal place cell activity associated with theta oscillations encodes spatial position during behavior, and theta-phase associated spiking is known to further mediate a temporal code for space within CA1 place fields. Although prefrontal neurons are prominently phase-locked to hippocampal theta oscillations in spatial memory tasks, whether and how theta oscillations mediate processing of spatial information across these networks remains unclear. Here, we addressed these questions using simultaneous recordings of dorsal CA1 - PFC ensembles and population decoding analyses in male rats performing a continuous spatial working memory task known to require hippocampal-prefrontal interactions. We found that in addition to CA1, population activity in PFC can also encode the animals current spatial position on a theta-cycle timescale during memory-guided behavior. Coding of spatial position was coherent for CA1 and PFC ensembles, exhibiting correlated position representations within theta cycles. In addition, incorporating theta-phase information during decoding to account for theta-phase associated spiking resulted in a significant improvement in the accuracy of prefrontal spatial representations, similar to concurrent CA1 representations. These findings indicate a theta-oscillation mediated mechanism of temporal coordination for shared processing and communication of spatial information across the two networks during spatial memory-guided behavior.

neuroscience↗

bioRxiv2018

Interaction of taste and place coding in the hippocampus

An animals survival depends on finding food, and the memory of food and contexts are often linked. Given that the hippocampus is required for spatial and contextual memory, it is reasonable to expect related coding of space and food stimuli in hippocampal neurons. However, relatively little is known about how the hippocampus responds to tastes, the most central sensory property of food. In this study, we examined the taste-evoked responses and spatial firing properties of single units in the dorsal CA1 hippocampal region as male rats received a battery of taste stimuli differing in both chemical composition and palatability within a specific spatial context. We identified a subset of hippocampal neurons that responded to tastes, some of which were place cells. These taste and place responses had a distinct interaction: taste-responsive cells tended to have less spatially specific firing fields, and place cells only responded to tastes delivered inside their place field. Like neurons in the amygdala and lateral hypothalamus, hippocampal neurons discriminated between tastes predominantly on the basis of palatability, with taste-selectivity emerging concurrently with palatability-relatedness; these responses did not reflect movement or arousal. However, hippocampal taste responses emerged several hundred msec later than responses in other parts of the taste system, suggesting that the hippocampus does not influence real-time taste decisions, instead associating the hedonic value of tastes with a particular context. This incorporation of taste responses into existing hippocampal maps could be one way that animals use past experience to locate food sources.\n\nSignificance statementFinding food is essential for animals survival, and taste and context memory are often linked. While hippocampal responses to space and contexts have been well characterized, little is known about how the hippocampus responds to tastes. Here, we identified a subset of hippocampal neurons that discriminated between tastes based on palatability. Cells with stronger taste responses typically had weaker spatial responses, and taste responses were confined to place cells firing fields. Hippocampal taste responses emerged later than in other parts of the taste system, suggesting that the hippocampus does not influence taste decisions, but rather, associates the hedonic value of tastes consumed within a particular context. This could be one way that animals use past experience to locate food sources.

neuroscience↗