Biology subjects

Blair, G. J.

Publications and source records attributed to Blair, G. J..

5 recordsLinked to original sources

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.

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↗

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.

neuroscience↗