Patterned, But Not Tonic, Optogenetic Stimulation in Motor Thalamus Improves Reaching in Acute Drug-Induced Parkinsonian Rats

Seeger-Armbruster, Sonja; Bosch‐Bouju, Clémentine; Little, Shane T C; Smither, Roseanna A; Hughes, Stephanie M.; Hyland, Brian I.; Parr‐Brownlie, Louise C.

doi:10.1523/jneurosci.3277-14.2015

Cited by 32 publications

(34 citation statements)

References 34 publications

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“…Taken together, these results suggest that activation of a subset of Gr43a-expressing neurons is sufficient to generate long-lasting associative memory. These observations further suggest that activation of the same neurons by different methods, perhaps leading to different activity levels/patterns, give rise to substantially different behavioral outcomes, consistent with other reports (Clark et al, 2013; Seeger-Armbruster et al, 2015). However, further work is necessary to determine exactly which subsets of neurons contribute to L-arabinose memory, and whether these neurons needs to be activated in a specific pattern to elicit long-term memory.…”

Section: Resultssupporting

confidence: 90%

Immediate perception of a reward is distinct from the reward’s long-term salience

McGinnis

Jiang

Agha

et al. 2016

eLife

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Reward perception guides all aspects of animal behavior. However, the relationship between the perceived value of a reward, the latent value of a reward, and the behavioral response remains unclear. Here we report that, given a choice between two sweet and chemically similar sugars—L- and D-arabinose—Drosophila melanogaster prefers D- over L- arabinose, but forms long-term memories of L-arabinose more reliably. Behavioral assays indicate that L-arabinose-generated memories require sugar receptor Gr43a, and calcium imaging and electrophysiological recordings indicate that L- and D-arabinose differentially activate Gr43a-expressing neurons. We posit that the immediate valence of a reward is not always predictive of the long-term reinforcement value of that reward, and that a subset of sugar-sensing neurons may generate distinct representations of similar sugars, allowing for rapid assessment of the salient features of various sugar rewards and generation of reward-specific behaviors. However, how sensory neurons communicate information about L-arabinose quality and concentration—features relevant for long-term memory—remains unknown.DOI: http://dx.doi.org/10.7554/eLife.22283.001

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Section: Resultssupporting

confidence: 90%

Immediate perception of a reward is distinct from the reward’s long-term salience

McGinnis

Jiang

Agha

et al. 2016

eLife

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“…Furthermore, large numbers of trials across many animals are often necessary to draw conclusions from single unit recordings. Patterned optogenetic stimulation has also been applied throughout the reaching task, including between reaches (Seeger-Armbruster et al, 2015). The ability to flexibly detect distinct reaching phases offers the potential to more fully exploit the power of specifically timed optogenetic interventions.…”

Section: Discussionmentioning

confidence: 99%

An automated rat single pellet reaching system with high-speed video capture

Ellens

Gaidica

Toader

et al. 2016

Journal of Neuroscience Methods

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Background Single pellet reaching is an established task for studying fine motor control in which rats reach for, grasp, and eat food pellets in a stereotyped sequence. Most incarnations of this task require constant attention, limiting the number of animals that can be tested and the number of trials per session. Automated versions allow more interventions in more animals, but must be robust and reproducible. New Method Our system automatically delivers single reward pellets for rats to grasp with their forepaw. Reaches are detected using real-time computer vision, which triggers video acquisition from multiple angles using mirrors. This allows us to record high-speed (>300 frames per second) video, and trigger interventions (e.g., optogenetics) with high temporal precision. Individual video frames are triggered by digital pulses that can be synchronized with behavior, experimental interventions, or recording devices (e.g., electrophysiology). The system is housed within a soundproof chamber with integrated lighting and ventilation, allowing multiple skilled reaching systems in one room. Results We show that rats acquire the automated task similarly to manual versions, that the task is robust, and can be synchronized with optogenetic interventions. Comparison with existing methods Existing skilled reaching protocols require high levels of investigator involvement, or, if ad libitum, do not allow for integration of high-speed, synchronized data collection. Conclusion This task will facilitate the study of motor learning and control by efficiently recording large numbers of skilled movements. It can be adapted for use with modern neurophysiology, which demands high temporal precision.

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“…The instructive information is mediated by bioelectric gradients per se, and not other functions of ion channel proteins or chemical signaling by specific ions: pattern can be predictably altered by specific modulation of those spatial gradients using any convenient channel or ion to achieve the desired change in V mem state 33, 36c . This offers the opportunity for bioengineers to use structured light (for optogenetic activation) 62 or substrates with embedded channel drugs 63 , to impose patterned bioelectrical states on in vitro constructs or regenerating tissues for augmented control of morphogenesis.…”

Section: Harnessing Non-neural Bioelectricity To Implement Organ-lmentioning

confidence: 99%

Re-membering the body: applications of computational neuroscience to the top-down control of regeneration of limbs and other complex organs

2015

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A major goal of regenerative medicine and bioengineering is the regeneration of complex organs, such as limbs, and the capability to create artificial constructs (so-called biobots) with defined morphologies and robust self-repair capabilities. Developmental biology presents remarkable examples of systems that self-assemble and regenerate complex structures toward their correct shape despite significant perturbations. A fundamental challenge is to translate progress in molecular genetics into control of large-scale organismal anatomy, and the field is still searching for an appropriate theoretical paradigm for facilitating control of pattern homeostasis. However, computational neuroscience provides many examples in which cell networks (brains) store memories of geometrical states and coordinate their activity towards proximal and distant goals. In this Perspective, we propose that programming large-scale morphogenesis requires exploiting the information processing by which cellular structures work toward specific shapes. In non-neural cells, as in the brain, bioelectric signaling implements information processing, decision-making, and memory in regulating pattern and its remodeling. Thus, approaches used in computational neuroscience to understand goal-seeking neural systems offer a toolbox of techniques to model and control regenerative pattern formation. Here, we review recent data on developmental bioelectricity as a regulator of patterning, and propose that target morphology could be encoded within tissues as a kind of memory, using the same molecular mechanisms and algorithms so successfully exploited by the brain. We highlight the next steps of an unconventional research program, which may allow top-down control of growth and form for numerous applications in regenerative medicine and synthetic bioengineering.

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Patterned, But Not Tonic, Optogenetic Stimulation in Motor Thalamus Improves Reaching in Acute Drug-Induced Parkinsonian Rats

Cited by 32 publications

References 34 publications

Immediate perception of a reward is distinct from the reward’s long-term salience

Immediate perception of a reward is distinct from the reward’s long-term salience

An automated rat single pellet reaching system with high-speed video capture

Re-membering the body: applications of computational neuroscience to the top-down control of regeneration of limbs and other complex organs

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