Biology subjects

Redish, A. D.

Publications and source records attributed to Redish, A. D..

14 recordsLinked to original sources

bioRxiv2026

Systemic diazepam alters local hippocampal CA1 circuits and differentially affects entorhinal and CA3 inputs

The GABAA positive allosteric modulator diazepam is taken systemically by millions of people daily. GABAA signaling is essential for hippocampal circuit function, but the effects of systemic diazepam on hippocampal information processing during behavior has not been studied. To answer this question, large neural ensembles were recorded from rats running a linear track under systemic diazepam administration. A cross-correlation of spiking activity revealed significantly increased inhibition from interneurons, aligned with the timescale of GABAA, suggesting a direct effect on local circuits. Local field potentials (LFP) showed an increase in theta and lo-gamma (30-50 Hz) power but a decrease in hi-gamma (80-120 Hz) power. We also found decreased amplitude and rate of sharp wave ripple (SWR) events and a reduction of firing rate and proportion of cells recruited to the SWRs. An autocorrelation of single-cell spike trains revealed a decrease and shift from shorter to longer timescales, aligning differently with theta frequencies. Phase coupling measurements showed decreased cellular coupling to theta and increased coupling to lo-gamma and hi-gamma. Finally, entropy of decoding along the track was increased, suggesting less precise spatial representations under diazepam. These changes suggest mechanisms that would likely disrupt hippocampal memory storage and consolidation processes under systemic diazepam.

neuroscience↗

bioRxiv2026

Measuring excitation/inhibition balance through field potentials

Several electroencephalography-based metrics have been proposed to index excitation/inhibition balance (E/I). We used single-unit and local field potential recordings from rat medial prefrontal and orbitofrontal cortex and mouse visual cortex and hippocampus to evaluate four candidate metrics against empirically-measured E/I. While 1/f slope and gamma oscillations showed region and context dependencies, broadband (6-80 Hz) and high gamma (80-150 Hz) power consistently correlated with E/I, supporting their use as proxy measures. If at least 30 minutes' data from medial prefrontal cortex were used per animal, broadband power could rank the animals by their E/I ratio, suggesting it could be used as an individual differences measure.

neuroscience↗

bioRxiv2026

Coordinated Representational Drift Across the Mouse Cortex

Cortical neurons continuously change their spatial tuning properties over days and weeks, yet how this representational drift is coordinated across distributed cortical networks remains unknown. Using a robotic cranial exoskeleton for chronic widefield calcium imaging with cellular resolution, we tracked over 110,000 unique layer 2/3 neurons across retrosplenial, visual, somatosensory, and motor cortices in mice navigating a figure-8 maze spanning 47 days. Single-neuron spatial tuning properties followed a posterior-to-anterior gradient, with retros-plenial and visual cortices containing the highest proportions of spatially tuned neurons. This was dissociated from local functional coupling, which was strongest in somatosensory cortex. Population activity formed a low-dimensional manifold whose geometry mirrored the structure of the maze. Despite these regional differences, all four regions decorrelated with similar exponential timescales, and session-specific deviations from each regions decay trajectory were correlated across all pairwise region combinations, suggesting that drift was coordinated rather than independent across the dorsal cortex. This coordination persisted after controlling for shared behavioral fluctuations. Furthermore, drift was consistent with an orthogonal transformation of the population code that preserved the geometric relationships between spatial representations across sessions despite continuous drift in single-neuron tuning.

neuroscience↗

bioRxiv2026

Hippocampal representations differentiate reactive and anticipatory responses during foraging under threat

Adaptive behavior under threat requires balancing reward pursuit against the risk of harm. During approach-avoidance conflict, animals often pause at decision points, but whether these pauses reflect a unified process or distinct decision states remains unclear. Here, we replicate and extend findings from Calvin et al. (2025) by analyzing hippocampal activity in rats performing a pseudo-predator foraging task across two cohorts. We compared mid-track aborts (MTAs), mid-track continues (MTCs), and retreats. Behaviorally, MTAs and MTCs emerged from a shared pause state but diverged in outcome, whereas retreats reflected rapid escape following attack. Despite similar endpoints, retreats and MTAs differed in movement dynamics and neural activity. During retreats, hippocampal representations remained biased toward the attack location. In contrast, representations during MTAs shifted toward safe locations. During pauses, representations differed according to subsequent behavior: pauses preceding MTAs showed greater decoded probability near the attack region, whereas pauses preceding MTCs showed greater decoded probability to goal locations. These differences were present during the outbound approach, suggesting decision-related processes emerged early on in the journey. Together, these findings dissociate hippocampal representations associated with reactive escape from those underlying anticipatory, anxiety-like decision-making, suggesting that the hippocampus dynamically tracks behaviorally relevant features to guide decisions under threat.

neuroscience↗

bioRxiv2024

Individual differences in decision-making shape how mesolimbic dopamine regulates choice confidence and change-of-mind

Nucleus accumbens dopamine signaling is an important neural substrate for decision-making. Dominant theories generally discretize and homogenize decision-making, when it is in fact a continuous process, with evaluation and re-evaluation components that extend beyond simple outcome prediction into consideration of past and future value. Extensive work has examined mesolimbic dopamine in the context of reward prediction error, but major gaps persist in our understanding of how dopamine regulates volitional and self-guided decision-making. Moreover, there is little consideration of individual differences in value processing that may shape how dopamine regulates decision-making. Here, using an economic foraging task in mice, we found that dopamine dynamics in the nucleus accumbens core reflected decision confidence during evaluation of decisions, as well as both past and future value during re-evaluation and change-of-mind. Optogenetic manipulations of mesolimbic dopamine release selectively altered evaluation and re-evaluation of decisions in mice whose dopamine dynamics and behavior reflected future value.

neuroscience↗

bioRxiv2024

A triple dissociation across the medial, ventral, and lateral orbitofrontal cortex in rats making sequential foraging decisions

Far medial and lateral aspects of the orbitofrontal cortex (OFC) serve distinct roles in value-based decision-making, though it remains unclear how more nearby lateral and ventral aspects differ in their information-processing characteristics. The present study leveraged high-density neural recording in the lateral orbital (LO) and ventral orbital (VO) subregions using a neuroeconomic task in rats to clarify how functional heterogeneity between LO and VO participates in sequential cost-benefit foraging. LO and VO contained opposing representations of an encountered rewards subjective benefit and its associated opportunity costs, respectively. The relative balance of these representations tracked decisions to approach or leave a reward during each stage of an encounter. Opposing representations of subjective benefit in LO and opportunity costs in VO were realized by distinct clusters of cells within each subregion across stages of a reward encounter (i.e., task state). In addition, overall activity in each subregion scaled with changes in the subjective value of rewards induced by external, economic conditions (reward scarcity) and internal, motivational factors (hunger). Collectively, these results suggest that lateral and ventral OFC encode opposing representations to guide sequential foraging decisions, but using a shared coding scheme which multiplexes information about subjective value (via overall activity) and world states (via distinct ensembles).

neuroscience↗

bioRxiv2024

Environmental complexity modulates information processing and the balance between decision-making systems

Behavior in naturalistic scenarios occurs in diverse environments. Adaptive strategies rely on multiple neural circuits and competing decision-systems. However, past studies of rodent decision-making have largely measured behavior in simple environments. To fill this gap, we recorded neural ensembles from hippocampus (HC), dorsolateral striatum (DLS), and medial prefrontal cortex (mPFC) while rats foraged for food under changing rules in environments with varying topological complexity. Environmental complexity increased behavioral variability, lengthened HC nonlocal sequences, and modulated action caching. We found contrasting representations between DLS and HC, supporting a competition between decision systems. mPFC activity was indicative of setting this balance, in particular predicting the extent of HC non-local coding. Inactivating mPFC impaired short-term behavioral adaptation and produced long-term deficits in balancing decision systems. Our findings reveal the dynamic nature of decision-making systems and how environmental complexity modulates their engagement with implications for behavior in naturalistic environments.

neuroscience↗

bioRxiv2024

Dorsal hippocampus represents locations to avoid as well as locations to approach during approach-avoidance conflict

Worrying about perceived threats is a hallmark of multiple psychological disorders including anxiety. This concern about future events is particularly important when an individual is faced with an approach-avoidance conflict. Potential goals to approach are known to be represented in the dorsal hippocampus during theta sweeps. Similarly, important non-local information is represented during hippocampal high synchrony events (HSEs), which are correlated with sharp-wave ripples (SWRs). It is likely that potential future threats may be similarly represented. We examined how threats and rewards were represented within the hippocampus during approach-avoidance conflicts in rats faced with a predator-like robot guarding a food reward. We found representations of the pseudo-predator during HSEs when hesitating in the nest, and during theta prior to retreating as the rats approached the pseudo-predator. After the first attack, we observed new place fields appearing at the location of the robot (not the location the rat was when attacked). The anxiolytic diazepam reduced anxiety-like behavior and altered hippocampal local field potentials, including reducing SWRs, suggesting that one potential mechanism of diazepams actions may be through altered representations of imagined threat. These results suggest that hippocampal representation of potential threats could be an important mechanism that underlies worry and a potential target for anxiolytics.

neuroscience↗

bioRxiv2024

Measuring excitation-inhibition balance through spectral components of local field potentials

The balance between excitation and inhibition is critical to brain functioning, and dysregulation of this balance is a hallmark of numerous psychiatric conditions. Measuring this excitation-inhibition (E:I) balance in vivo has remained difficult, but theoretical models have proposed that characteristics of local field potentials (LFP) may provide an accurate proxy. To establish a conclusive link between LFP and E:I balance, we recorded single units and LFP from the prefrontal cortex (mPFC) of rats during decision making. Dynamic measures of synaptic coupling strength facilitated direct quantification of E:I balance and revealed a strong inverse relationship to broadband spectral power of LFP. These results provide a critical link between LFP and underlying network properties, opening the door for non-invasive recordings to measure E:I balance in clinical settings.

neuroscience↗

bioRxiv2023

Distinct mesoscale cortical dynamics encode search strategies during spatial navigation

Spatial navigation is a complex cognitive process that involves neural computations in distributed regions of the brain. Little is known about how cortical regions are coordinated when animals navigate novel spatial environments or how that coordination changes as environments become familiar. We recorded mesoscale calcium (Ca2+) dynamics across large swathes of the dorsal cortex in mice solving the Barnes maze, a 2D spatial navigation task where mice used random, serial, and spatial search strategies to navigate to the goal. Cortical dynamics exhibited patterns of repeated calcium activity with rapid and abrupt shifts between cortical activation patterns at sub-second time scales. We used a clustering algorithm to decompose the spatial patterns of cortical calcium activity in a low dimensional state space, identifying 7 states, each corresponding to a distinct spatial pattern of cortical activation, sufficient to describe the cortical dynamics across all the mice. When mice used serial or spatial search strategies to navigate to the goal, the frontal regions of the cortex were reliably activated for prolonged durations of time (> 1s) shortly after trial initiation. These frontal cortex activation events coincided with mice approaching the edge of the maze from the center and were preceded by temporal sequences of cortical activation patterns that were distinct for serial and spatial search strategies. In serial search trials, frontal cortex activation events were preceded by activation of the posterior regions of the cortex followed by lateral activation of one hemisphere. In spatial search trials, frontal cortical events were preceded by activation of posterior regions of the cortex followed by broad activation of the lateral regions of the cortex. Our results delineated cortical components that differentiate goal- and non-goal oriented spatial navigation strategies.

neuroscience↗

bioRxiv2023

Reward prediction-errors weighted by cue salience produces addictive behaviors in simulations, with asymmetrical learning and steeper delay discounting

Dysfunction in learning and motivational systems are thought to contribute to addictive behaviours. Previous models have suggested that dopaminergic roles in learning and motivation could produce addictive behaviours through pharmacological manipulations that provide excess dopaminergic signalling towards these learning and motivational systems. Redish 2004 suggested a role based on dopaminergic signals of value prediction error, while Zhang et al. 2009 suggested a role based on dopaminergic signals of motivation. Both these models present significant limitations. They do not explain the reduced sensitivity to drug-related costs/negative consequences, the increased impulsivity generally found in people with a substance use disorder, craving behaviours, and non-pharmacological dependence, all of which are key hallmarks of addictive behaviours. Here, we propose a novel mathematical definition of salience, that combines aspects of dopamines role in both, learning and motivation, within the reinforcement learning framework. Using a single parameter regime, we simulated addictive behaviours that the Zhang et al. 2009 and Redish 2004 models also produce but we went further in simulating the downweighting of drug-related negative prediction-errors, steeper delay discounting of drug rewards, craving behaviours and aspects of behavioural/non-pharmacological addictions. The current salience model builds on our recently proposed conceptual theory that salience modulates internal representation updating and may contribute to addictive behaviours by producing misaligned internal representations (Kalhan et al., 2021). Critically, our current mathematical model of salience argues that the seemingly disparate learning and motivational aspects of dopaminergic functioning may interact through a salience mechanism that modulates internal representation updating.

neuroscience↗

bioRxiv2022

Differential processing of decision information in subregions of rodent medial prefrontal cortex

Decision-making involves multiple cognitive processes requiring different aspects of information about the situation at hand. The rodent medial prefrontal cortex (mPFC) has been hypothesized to be central to these abilities. Functional studies have sought to link specific processes to specific anatomical subregions, but past studies of mPFC have yielded controversial results, leaving the precise nature of mPFC function unclear. To settle this debate, we recorded from the full dorso-ventral extent of mPFC in each of 8 rats, as they performed a complex economic decision task. These data revealed four distinct functional domains within mPFC that closely mirrored anatomically-identified subregions, including novel evidence to divide prelimbic cortex into dorsal and ventral components. We found that dorsal aspects of mPFC (ACC, dPL) were more involved in processing information about active decisions, while ventral aspects (vPL, IL) were more engaged in motivational factors. Impact StatementDiehl and Redish describe how the rodent medial prefrontal cortex is composed of functionally distinct subregions that process economic decision information differentially along a dorso-ventral gradient.

neuroscience↗

bioRxiv2021

Sunk cost sensitivity in mice, rats, and humans on the Restaurant Row and WebSurf tasks cannot be explained by attrition biases alone

In a recent bioRxiv preprint, Ott et al. argue that sensitivities to sunk costs that have been reported in two serial foraging tasks (the Restaurant Row task in mice and rats, and the Web-Surf task in humans) may be due to simple consequences of the way that subjects perform these tasks and not due to an actual sensitivity to sunk costs. However, several variants of these tasks have been studied, in which the sensitivity to sunk costs changes. In order to test the Ott et al. model against these experimental observations, we simulated the model under these additional experimental conditions. We find that it is incompatible with the actual data. While we applaud the simplicity of the Ott et al. model, we must reject it as an explanation for the observed sensitivity to sunk costs seen in these tasks. We thus conclude that the alternative explanation - that mice, rats, and humans are sensitive to actual sunk costs in these tasks - is a better explanation for the data.

neuroscience↗

bioRxiv2019

Divergent strategies for learning in males and females

A frequent assumption in value-based decision-making tasks is that agents make decisions based on the feature dimension that reward probabilities vary on. However, in complex, multidimensional environments, stimuli can vary on multiple dimensions at once, meaning that the feature deserving the most credit for outcomes is not always obvious. As a result, individuals may vary in the strategies used to sample stimuli across dimensions, and these strategies may have an unrecognized influence on decision-making. Sex is a proxy for multiple genetic and endocrine influences that can influence decision-making strategies, including how environments are sampled. In this study, we examined the strategies adopted by female and male mice as they learned the value of stimuli that varied in both image and location in a visually-cued two-armed bandit, allowing two possible dimensions to learn about. Female mice acquired the correct image-value associations more quickly than male mice, and they used a fundamentally different strategy to do so. Female mice constrained their decision-space early in learning by preferentially sampling one location over which images varied. Conversely, male strategies were inconsistent, changing frequently and strongly influenced by the immediate experience of stochastic rewards. Individual strategies were related to sex-gated changes in neuronal activation in early learning. Together, we find that in mice, sex is linked with divergent strategies for sampling and learning about the world, revealing substantial unrecognized variability in the approaches implemented during value-based decision-making.

animal behavior and cognition↗