Automated home cage training of mice in a hold-still center-out reach task

An obstacle to understanding neural mechanisms of movement is the complex, distributed nature of the mammalian motor system. Here we present a novel behavioral paradigm for high-throughput dissection of neural circuits underlying mouse forelimb control. Custom touch-sensing joysticks were used to quantify mouse forelimb trajectories with micron-millisecond spatiotemporal resolution. Joysticks were integrated into computer-controlled, rack-mountable home cages, enabling batches of mice to be trained in parallel. Closed loop behavioral analysis enabled online control of reward delivery for automated training. We used this system to show that mice can learn, with no human handling, a direction-specific hold-still center-out reach task in which a mouse first held its right forepaw still before reaching out to learned spatial targets. Stabilogram diffusion analysis of submillimeter-scale micromovements produced during the hold demonstrate that an active control process, akin to upright balance, was implemented to maintain forepaw stability. Trajectory decomposition methods, previously used in primates, were used to segment hundreds of thousands of forelimb trajectories into millions of constituent kinematic primitives. This system enables rapid dissection of neural circuits for controlling motion primitives from which forelimb sequences are built. NEW & NOTEWORTHY A novel joystick design resolves mouse forelimb kinematics with micron-millisecond precision. Home cage training is used to train mice in a hold-still center-out reach task. Analytical methods, previously used in primates, are used to decompose mouse forelimb trajectories into kinematic primitives.

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Stabilogram diffusion analysis algorithm to estimate the Hurst exponent of high-dimensional fractals

Journal of Statistical Mechanics Theory and Experiment ◽

10.1088/1742-5468/2012/04/p04014 ◽

2012 ◽

Vol 2012 (04) ◽

pp. P04014

Author(s):

Oleg Gorshkov

Keyword(s):

Hurst Exponent ◽

High Dimensional ◽

Analysis Algorithm ◽

Stabilogram Diffusion Analysis ◽

Diffusion Analysis

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Postural control model interpretation of stabilogram diffusion analysis

Biological Cybernetics ◽

10.1007/s004220050587 ◽

2000 ◽

Vol 82 (4) ◽

pp. 335-343 ◽

Cited By ~ 241

Author(s):

Robert J. Peterka

Keyword(s):

Postural Control ◽

Control Model ◽

Model Interpretation ◽

Stabilogram Diffusion Analysis ◽

Diffusion Analysis

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Dual-color volumetric imaging of neural activity of cortical columns

10.1101/504233 ◽

2018 ◽

Cited By ~ 1

Author(s):

Shuting Han ◽

Weijian Yang ◽

Rafael Yuste

Keyword(s):

Neural Activity ◽

High Speed ◽

Neural Circuits ◽

Emergent Properties ◽

Spatiotemporal Resolution ◽

Population Activity ◽

Volumetric Imaging ◽

Two Photon ◽

Dual Color

To capture the emergent properties of neural circuits, high-speed volumetric imaging of neural activity at cellular resolution is desirable. But while conventional two-photon calcium imaging is a powerful tool to study population activity in vivo, it is restrained to two-dimensional planes. Expanding it to 3D while maintaining high spatiotemporal resolution appears necessary. Here, we developed a two-photon microscope with dual-color laser excitation that can image neural activity in a 3D volume. We imaged the neuronal activity of primary visual cortex from awake mice, spanning from L2 to L5 with 10 planes, at a rate of 10 vol/sec, and demonstrated volumetric imaging of L1 long-range PFC projections and L2/3 somatas. Using this method, we map visually-evoked neuronal ensembles in 3D, finding a lack of columnar structure in orientation responses and revealing functional correlations between cortical layers which differ from trial to trial and are missed in sequential imaging. We also reveal functional interactions between presynaptic L1 axons and postsynaptic L2/3 neurons. Volumetric two-photon imaging appears an ideal method for functional connectomics of neural circuits.

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Imaging Voltage with Microbial Rhodopsins

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.738829 ◽

2021 ◽

Vol 8 ◽

Author(s):

Xiao Min Zhang ◽

Tatsushi Yokoyama ◽

Masayuki Sakamoto

Keyword(s):

Membrane Potential ◽

Brain Function ◽

Critical Parameter ◽

Neural Circuits ◽

Superior Performance ◽

Neuronal Dynamics ◽

Spatiotemporal Resolution ◽

Invasive Approach ◽

Electrophysiological Recordings ◽

Genetic Specificity

Membrane potential is the critical parameter that reflects the excitability of a neuron, and it is usually measured by electrophysiological recordings with electrodes. However, this is an invasive approach that is constrained by the problems of lacking spatial resolution and genetic specificity. Recently, the development of a variety of fluorescent probes has made it possible to measure the activity of individual cells with high spatiotemporal resolution. The adaptation of this technique to image electrical activity in neurons has become an informative method to study neural circuits. Genetically encoded voltage indicators (GEVIs) can be used with superior performance to accurately target specific genetic populations and reveal neuronal dynamics on a millisecond scale. Microbial rhodopsins are commonly used as optogenetic actuators to manipulate neuronal activities and to explore the circuit mechanisms of brain function, but they also can be used as fluorescent voltage indicators. In this review, we summarize recent advances in the design and the application of rhodopsin-based GEVIs.

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Circuits that encode and predict alcohol associated preference

10.1101/578401 ◽

2019 ◽

Cited By ~ 3

Author(s):

Kristin M. Scaplen ◽

Mustafa Talay ◽

Sarah Salamon ◽

Kavin M. Nuñez ◽

Amanda G. Waterman ◽

...

Keyword(s):

Memory Consolidation ◽

Mushroom Body ◽

Neural Circuits ◽

Population Level ◽

Dopamine Neurons ◽

Behavioral Choice ◽

Neuron Activation ◽

Reward Delivery ◽

Output Neurons ◽

Insight Into

AbstractSubstance use disorders are chronic relapsing disorders often impelled by enduring memories and persistent cravings. Alcohol, as well as other addictive substances, remolds neural circuits important for memory to establish obstinate preference despite aversive consequences. How pertinent circuits are selected and shaped to result in these unchanging, inflexible memories is unclear. Using neurogenetic tools available inDrosophila melanogasterwe define how circuits required for alcohol associated preference shift from population level dopaminergic activation to select dopamine neurons that predict behavioral choice. During memory expression, these dopamine neurons directly, and indirectly via the mushroom body (MB), modulate the activity of interconnected glutamatergic and cholinergic output neurons. Transsynaptic tracing of these output neurons revealed at least two regions of convergence: 1) a center of memory consolidation within the MB implicated in arousal, and 2) a structure outside the MB implicated in integration of naïve and learned responses. These findings provide a circuit framework through which dopamine neuron activation shifts from reward delivery to cue onset, and provides insight into the inflexible, maladaptive nature of alcohol associated memories.

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A genetically encoded fluorescent sensor for in vivo imaging of GABA

10.1101/322578 ◽

2018 ◽

Cited By ~ 4

Author(s):

Jonathan S. Marvin ◽

Yoshiteru Shimoda ◽

Vincent Malgoire ◽

Marco Leite ◽

Takashi Kawashima ◽

...

Keyword(s):

Neural Circuits ◽

Fluorescent Sensor ◽

Gaba Release ◽

Library Screening ◽

Spatiotemporal Resolution ◽

Fluorescent Reporter ◽

Inhibitory Neurotransmitter ◽

Single Action ◽

Gaba Content

AbstractCurrent techniques for monitoring GABA, the primary inhibitory neurotransmitter in vertebrates, cannot follow ephemeral transients in intact neural circuits. We applied the design principles used to create iGluSnFR, a fluorescent reporter of synaptic glutamate, to develop a GABA sensor using a protein derived from a previously unsequenced Pseudomonas fluorescens strain. Structure-guided mutagenesis and library screening led to a usable iGABASnFR (ΔF/Fmax ~ 2.5, Kd ~ 9 μM, good specificity, adequate kinetics). iGABASnFR is genetically encoded, detects single action potential-evoked GABA release events in culture, and produces readily detectable fluorescence increases in vivo in mice and zebrafish. iGABASnFR enabled tracking of: (1) mitochondrial GABA content and its modulation by an anticonvulsant; (2) swimming-evoked GABAergic transmission in zebrafish cerebellum; (3) GABA release events during inter-ictal spikes and seizures in awake mice; and (4) GABAergic tone decreases during isoflurane anesthesia. iGABASnFR will permit high spatiotemporal resolution of GABA signaling in intact preparations.

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Generalizability of Stabilogram Diffusion Analysis of center of pressure measures

Gait & Posture ◽

10.1016/j.gaitpost.2007.03.013 ◽

2008 ◽

Vol 27 (2) ◽

pp. 223-230 ◽

Cited By ~ 24

Author(s):

Richard J. Doyle ◽

Brian G. Ragan ◽

Karthikeyan Rajendran ◽

Karl S. Rosengren ◽

Elizabeth T. Hsiao-Wecksler

Keyword(s):

Center Of Pressure ◽

Stabilogram Diffusion Analysis ◽

Diffusion Analysis

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Circuits that encode and guide alcohol-associated preference

eLife ◽

10.7554/elife.48730 ◽

2020 ◽

Vol 9 ◽

Cited By ~ 3

Author(s):

Kristin M Scaplen ◽

Mustafa Talay ◽

Kavin M Nunez ◽

Sarah Salamon ◽

Amanda G Waterman ◽

...

Keyword(s):

Memory Consolidation ◽

Mushroom Body ◽

Neural Circuits ◽

Population Level ◽

Dopamine Neurons ◽

Adaptive Memory ◽

Behavioral Choice ◽

Reward Delivery ◽

Output Neurons ◽

Insight Into

A powerful feature of adaptive memory is its inherent flexibility. Alcohol and other addictive substances can remold neural circuits important for memory to reduce this flexibility. However, the mechanism through which pertinent circuits are selected and shaped remains unclear. We show that circuits required for alcohol-associated preference shift from population level dopaminergic activation to select dopamine neurons that predict behavioral choice in Drosophila melanogaster. During memory expression, subsets of dopamine neurons directly and indirectly modulate the activity of interconnected glutamatergic and cholinergic mushroom body output neurons (MBON). Transsynaptic tracing of neurons important for memory expression revealed a convergent center of memory consolidation within the mushroom body (MB) implicated in arousal, and a structure outside the MB implicated in integration of naïve and learned responses. These findings provide a circuit framework through which dopamine neuronal activation shifts from reward delivery to cue onset, and provide insight into the maladaptive nature of memory.

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