Biology subjects

Blair, H. T.

Publications and source records attributed to Blair, H. T..

14 recordsLinked to original sources

bioRxiv2026

Path Integration Promotes Flexible Navigational Decision Making

Flexible decision making depends on internal representations that capture the latent structure of a task, allowing prior knowledge to be applied in novel circumstances. Spatial navigation provides a useful model for studying flexible choice behavior, because spatial location is itself a latent variable that must be inferred rather than directly perceived. Here, we trained rats on a navigation task that required them to reach the same goal via two distinct paths from different starting locations, and then return to one of the two starting locations before beginning the next trial. Some rats were trained to rely on distal visual landmarks, allowing task states to be identified from current sensory information, whereas others were trained to rely on path integration, requiring task states to be inferred from self-motion information accumulated over the preceding trajectory. Rats trained to rely on path integration acquired the task similarly to rats trained to rely on distal visual landmarks. However, reliance on path integration enhanced rats' ability to generalize their learning to novel situations, including finding the goal from an untrained starting location and adapting to a relocated goal that reversed learned choice sequences. These findings suggest that reliance on path integration promotes the acquisition and use of mental representations that capture the latent spatial structure of navigational tasks, thereby favoring flexible navigational decisions over rigid retrieval of reinforced responses. More broadly, our findings demonstrate how information available during training can shape representations learned from experience and thereby constrain the flexibility of decision making during inference.

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bioRxiv2026

Habit and the hippocampus: Model-based spatial representations without outcome-sensitive control

Goal-directed decisions depend on predictions of future outcomes and are thus sensitive to revaluation of expected outcomes, whereas habitual decisions depend on cached action values or stimulus-response associations and are insensitive to outcome revaluation. Hippocampal neurons encode future states (potentially supporting prediction of future outcomes during goal-directed choice) as well as present states (potentially supporting retrieval of state-dependent action values during habitual choice). Prior studies suggest a role for the hippocampus in goal-directed, outcome-sensitive decision making, but few studies have examined its role in habitual, outcome-insensitive action selection. Here, we tested this using a two-outcome spatial navigation task in which identical turning actions (left or right) led either to preferred milk or non-preferred water outcomes, depending on the spatial location at which the choice was made. Rats (20 males, 22 females) were trained under conditions that either required hippocampal-dependent discrimination between choice points or allowed hippocampal-independent navigation using visual beacons. Rats then underwent 24 h water restriction during which separate cohorts underwent Contingency Updating (CU), in which rats re-experienced the maze action-outcome contingencies while thirsty, or Incentive Learning (IL), in which rats received only a two-bottle preference test while thirsty without re-experiencing maze contingencies. Both cohorts were later tested under thirst on an unbaited maze. CU rats shifted their choices toward water-associated responses, whereas IL rats perseverated on milk-associated responses, even when navigation depended on the hippocampus. These results provide novel evidence that hippocampal-dependent navigational decisions can show insensitivity to outcome revaluation, a widely-used behavioral criterion for habitual control. Significance StatementWe show here that the dorsal hippocampus can support navigational decisions that are insensitive to outcome revaluation during a spatial task in which identical actions lead to different outcomes depending on location. Even when the hippocampus was required for accurate navigation to reach a preferred outcome, rats overtrained on this task failed to adjust their choices after revaluation altered their outcome preferences. To our knowledge, these findings provide the first direct evidence that hippocampal-dependent navigation can satisfy a widely used behavioral criterion for habitual control.

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bioRxiv2025

Striatal cell-type specific stability and reorganization underlying agency and habit

Goal-directed behavior is guided by learned action-outcome associations, allowing actions to adapt when outcomes change. With repetition, behavioral control shifts toward habit, enabling more automatic action execution, but reducing flexibility to outcome changes. Here, we used longitudinal, cellular-resolution calcium imaging, chemogenetics, instrumental conditioning, and the outcome devaluation test to ask how dorsomedial striatum D1+ and D2/A2A+ neurons contribute to the formation of goal-directed behavior and habit. DMS D1+ neurons stably encode instrumental actions, carry information about behavioral engagement and organization, and develop and maintain action-reward representational similarity and conjunctive activation with learning. Correspondingly, these neurons are critical for action-outcome learning and goal-directed decision making. In contrast, one ensemble of DMS A2A+ neurons transiently encodes actions during early action-outcome learning and another slowly starts to encode actions as habits form. Similarly, DMS A2A+ neurons transiently mediate action-outcome learning and become dispensable for goal-directed decision making. Thus, action-outcome associations are learned through DMS D1+ and A2A+ neuronal activity but only DMS D1+ neurons maintain support of adaptive, goal-directed decision making. Habit formation is associated with reorganization of A2A+ neuronal encoding. These data reveal a cell-type-specific dissociation between stable v. reorganizing striatal action representations paralleled by persistent v. transient contributions to goal-directed control.

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bioRxiv2024

Neural coding of choice and outcome are modulated by uncertainty in orbitofrontal but not secondary motor cortex

Orbitofrontal cortex (OFC) and secondary motor cortex (M2) are both implicated in flexible reward learning but the conditions that differentially recruit these regions are not fully understood. We imaged calcium activity from single neurons in OFC or M2 during de novo learning of increasingly uncertain reward probability schedules. Predictions of choice were decoded from M2 neurons with high accuracy under all certainty conditions, but were more accurately decoded from OFC neurons under greater uncertainty. The number of choice- and reward-selective neurons was significantly higher in M2 than in OFC across schedules, but these proportions increased across levels of uncertainty only in OFC. Decoding accuracy of choice and outcome was predicted by behavioral strategies Win-Stay and Lose-Shift in OFC, but not M2. We also tested causal involvement of these regions with chemogenetic perturbation as rats learned increasing and then decreasing uncertainty schedules. Whereas inhibition of OFC neurons attenuated learning across all schedules, M2 neurons were found to support learning in the most certain reward schedule. Thus, OFC neurons preferentially encode choices and outcomes that foster a greater reliance on adaptive strategies under uncertainty. This reveals a novel functional heterogeneity within frontal cortex in support of flexible learning.

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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.

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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.

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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.

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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.

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bioRxiv2021

Theta oscillations in frontal cortex differentially modulate accuracy and speed in flexible stimulus- and action-based learning

Flexible reward learning relies on frontal cortex, with substantial evidence indicating that anterior cingulate cortex (ACC) and orbitofrontal cortex (OFC) subregions play important roles. Recent studies in both rat and macaque suggest theta oscillations (5-10 Hz) may be a spectral signature that coordinates this learning. However, network-level interactions between ACC and OFC in flexible learning remain unclear. We investigated the learning of stimulus-reward associations using a combination of simultaneous in-vivo electrophysiology in dorsal ACC and ventral OFC, partnered with bilateral inhibitory DREADDs in ACC. In freely-behaving male and female rats and using a within-subject design, we examined accuracy and speed of response across distinct and precisely-defined trial epochs during initial visual discrimination learning and subsequent reversal of stimulus-reward contingencies. Following ACC inhibition there was a propensity for random responding in early reversal learning, with correct vs. incorrect trials distinguished only from OFC, not ACC, theta power differences in the reversal phase. ACC inhibition also hastened incorrect choices during reversal. This same pattern of change in accuracy and speed was not observed in viral control animals. Thus, characteristics of impaired reversal learning following ACC inhibition are poor deliberation and weak theta signaling of accuracy in this region. The present results also point to OFC theta oscillations as a prominent feature of reversal learning, unperturbed by ACC inhibition.

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bioRxiv2020

Excitatory and inhibitory modulation of septal and striatal neurons during hippocampal sharp-wave ripple events

Single-units were recorded in hippocampus, septum, and striatum while freely behaving rats (n=3) ran trials in a T-maze task, and rested in a holding bucket between trials. During periods of motor inactivity, SWRs triggered excitatory responses from 28% (64/226) and inhibitory responses from 14% (31/226) of septal neurons. By contrast, only 4% (14/378) of striatal neurons were excited and 6% (24/378) were inhibited during SWRs. In both structures, SWR-responsive neurons exhibited greater spike coherence with hippocampal theta rhythm than neurons that did not respond to SWRs. In septum, neurons that were excited by SWRs fired at late phases of the theta cycle, whereas neurons that were inhibited by SWRs fired at early phases of the theta cycle. By contrast, SWR-responsive striatal neurons did not show consistent phase preferences during the theta cycle. A subset of SWR-responsive neurons in septum (55/95) and striatum (26/38) behaved as speed cells, with firing rates that were positively or negatively modulated by the rats running speed. In both structures, firing rates of most SWR-excited speed cells were positively modulated by running speed, whereas firing rates of most SWR-inhibited speed cells were negatively modulated by running speed. These findings are consistent with a growing body of evidence that SWRs can activate subcortical representations of motor actions in conjunction with hippocampal representations of places and states, which may be important for storing and retrieving values of state-action pairs during reinforcement learning and memory consolidation.

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bioRxiv2019

Anterior cingulate cortex activity regulates effort-based decision making

The anterior cingulate cortex (ACC) is implicated in effort exertion and choices based on effort cost, but it is still unclear how it mediates this cost-benefit evaluation. Here, male rats were trained to exert effort for a high-value reward (sucrose pellets) in a progressive ratio lever pressing task. Trained rats were then tested in two conditions: a no-choice condition where lever pressing for sucrose was the only available food option, and a choice condition where a low-value reward (lab chow) was freely available as an alternative to pressing for sucrose. Disruption of ACC--via either chemogenetic inhibition or excitation--reduced lever pressing in the choice, but not in the no-choice, condition. We next looked for value coding cells in ACC during effortful behavior and reward consumption phases during choice and no-choice conditions. For this, we utilized in vivo miniaturized fluorescence microscopy to reliably track responses of the same cells and compare how ACC neurons respond during the same effortful behavior where there was a choice versus when there was no-choice. We found that lever-press and sucrose-evoked responses were significantly weaker during choice compared to no-choice sessions, which may have rendered them more susceptible to chemogenetic disruption. Taken together, findings from our interference experiments and neural recordings suggest that a mechanism by which ACC mediates effortful decisions is in the discrimination of the utility of available options. ACC regulates these choices by providing a stable population code for the relative value of different options. Significance StatementThe anterior cingulate cortex (ACC) is implicated in effort-based decision making. Here, we used chemogenetics and in vivo calcium imaging to explore its mechanism. Rats were trained to lever press for a high-value reward and tested in two conditions: a no-choice condition where lever pressing for the high-value reward was the only option, and a choice condition where a low-value reward was also available. Inhibition or excitation of ACC reduced effort toward the high value option, but only in the choice condition. Neural responses in ACC were weaker in the choice compared to the no-choice condition. A mechanism by which ACC regulates effortful decisions is in providing a stable population code for the discrimination of the utility of available options.

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bioRxiv2019

An uncertainty principle for neural coding: Conjugate representations of position and velocity are mapped onto firing rates and co-firing rates of neural spike trains

The hippocampal system contains neural populations that encode an animals position and velocity as it navigates through space. Here, we show that such populations can embed two codes within their spike trains: a firing rate code (R) conveyed by within-cell spike intervals, and a co-firing rate code ([R]) conveyed by between-cell spike intervals. These two codes behave as conjugates of one another, obeying an analog of the uncertainty principle from physics: information conveyed in R comes at the expense of information in[R] , and vice versa. An exception to this trade-off occurs when spike trains encode a pair of conjugate variables, such as position and velocity, which do not compete for capacity across R and[R] . To illustrate this, we describe two biologically inspired methods for decoding R and[R] , referred to as sigma and sigma-chi decoding, respectively. Simulations of head direction (HD) and grid cells show that if firing rates are tuned for position (but not velocity), then position is recovered by sigma decoding, whereas velocity is recovered by sigma-chi decoding. Conversely, simulations of oscillatory interference among theta-modulated "speed cells" show that if co-firing rates are tuned for position (but not velocity), then position is recovered by sigma-chi decoding, whereas velocity is recovered by sigma decoding. Between these two extremes, information about both variables can be distributed across both channels, and partially recovered by both decoders. These results suggest that neurons with different spatial and temporal tuning properties--such as speed versus grid cells--might not encode different information, but rather, distribute similar information about position and velocity in different ways across R and[R] . Such conjugate coding of position and velocity may influence how hippocampal populations are interconnected to form functional circuits, and how biological neurons integrate their inputs to decode information from firing rates and spike correlations.

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bioRxiv2018

Recalibration of path integration in hippocampal place cells

Hippocampal place cells are spatially tuned neurons that serve as elements of a \"cognitive map\" in the mammalian brain1. To detect the animals location, place cells are thought to rely upon two interacting mechanisms: sensing the animals position relative to familiar landmarks2,3 and measuring the distance and direction that the animal has travelled from previously occupied locations4-7. The latter mechanism, known as path integration, requires a finely tuned gain factor that relates the animals self-movement to the updating of position on the internal cognitive map, with external landmarks necessary to correct positional error that eventually accumulates8,9. Path-integration-based models of hippocampal place cells and entorhinal grid cells treat the path integration gain as a constant9-14, but behavioral evidence in humans suggests that the gain is modifiable15. Here we show physiological evidence from hippocampal place cells that the path integration gain is indeed a highly plastic variable that can be altered by persistent conflict between self-motion cues and feedback from external landmarks. In a novel, augmented reality system, visual landmarks were moved in proportion to the animals movement on a circular track, creating continuous conflict with path integration. Sustained exposure to this cue conflict resulted in predictable and prolonged recalibration of the path integration gain, as estimated from the place cells after the landmarks were extinguished. We propose that this rapid plasticity keeps the positional update in register with the animals movement in the external world over behavioral timescales (mean 50 laps over 35 minutes). These results also demonstrate that visual landmarks not only provide a signal to correct cumulative error in the path integration system, as has been previously shown4,8,16-19, but also rapidly fine-tune the integration computation itself.

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bioRxiv2017

Spatial theta cells in competitive burst synchronization networks: Reference frames from phase codes

Spatial cells of the hippocampal formation are embedded in networks of theta cells. The septal theta rhythm (6-10 Hz) organizes the spatial activity of place and grid cells in time, but it remains unclear how spatial reference points organize the temporal activity of theta cells in space. We study spatial theta cells in simulations and single-unit recordings from exploring rats to ask whether temporal phase codes may anchor spatial representations to the outside world. We theorize that an experience-independent mechanism for temporal coding may combine with burst synchronization to continuously calibrate self-motion to allocentric reference frames. Subcortical recordings revealed spatial theta cells with strong rate-phase correlations related to distinct theta phases. Simulations of bursting neurons and networks explained that relationship and, with competitive learning, demonstrated flexible spatial synchronization patterns when driven by low-dimensional spatial components from the recording data. Thus temporal coding synchrony may reconcile extrinsic and intrinsic neural codes.

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