Dataset Information

Miniscope GRIN Lens System for Calcium Imaging of Neuronal Activity from Deep Brain Structures in Behaving Animals.

ABSTRACT: Visualizing neural activity from deep brain regions in freely behaving animals through miniature fluorescent microscope (miniscope) systems is becoming more important for understanding neural encoding mechanisms underlying cognitive functions. Here we present our custom-designed miniscope GRadient INdex (GRIN) lens system that enables simultaneously recording from hundreds of neurons for months. This article includes miniscope design, the surgical procedure for GRIN lens implantation, miniscope mounting on the head of a mouse, and data acquisition and analysis. First, a target brain region is labeled with virus expressing GCaMP6; second, a GRIN lens is implanted above the target brain region; third, following mouse surgical recovery, a miniscope is mounted on the head of the mouse above the GRIN lens; and finally, neural activity is recorded from the freely behaving mouse. This system can be applied to recording the same population of neurons longitudinally, enabling the elucidation of neural mechanisms underlying behavioral control. © 2018 by John Wiley & Sons, Inc.

SUBMITTER: Zhang L

PROVIDER: S-EPMC6318019 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Miniscope GRIN Lens System for Calcium Imaging of Neuronal Activity from Deep Brain Structures in Behaving Animals.

Zhang Lifeng L Liang Bo B Barbera Giovanni G Hawes Sarah S Zhang Yan Y Stump Kyle K Baum Ira I Yang Yupeng Y Li Yun Y Lin Da-Ting DT

Current protocols in neuroscience 20181013 1

Visualizing neural activity from deep brain regions in freely behaving animals through miniature fluorescent microscope (miniscope) systems is becoming more important for understanding neural encoding mechanisms underlying cognitive functions. Here we present our custom-designed miniscope GRadient INdex (GRIN) lens system that enables simultaneously recording from hundreds of neurons for months. This article includes miniscope design, the surgical procedure for GRIN lens implantation, miniscope ...[more]

PMID: 30315730

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Project description:Therapeutic drugs for cognitive and psychiatric disorders are often characterized by their molecular mechanism of action. Here we demonstrate a new approach to elucidate drug action on large-scale neuronal activity by tracking somatic calcium dynamics in hundreds of CA1 hippocampal neurons of pharmacologically manipulated behaving mice. We used an adeno-associated viral vector to express the calcium sensor GCaMP3 in CA1 pyramidal cells under control of the CaMKII promoter and a miniaturized microscope to observe cellular dynamics. We visualized these dynamics with and without a systemic administration of Zolpidem, a GABAA agonist that is the most commonly prescribed drug for the treatment of insomnia in the United States. Despite growing concerns about the potential adverse effects of Zolpidem on memory and cognition, it remained unclear whether Zolpidem alters neuronal activity in the hippocampus, a brain area critical for cognition and memory. Zolpidem, when delivered at a dose known to induce and prolong sleep, strongly suppressed CA1 calcium signaling. The rate of calcium transients after Zolpidem administration was significantly lower compared to vehicle treatment. To factor out the contribution of changes in locomotor or physiological conditions following Zolpidem treatment, we compared the cellular activity across comparable epochs matched by locomotor and physiological assessments. This analysis revealed significantly depressive effects of Zolpidem regardless of the animal's state. Individual hippocampal CA1 pyramidal cells differed in their responses to Zolpidem with the majority (∼ 65%) significantly decreasing the rate of calcium transients, and a small subset (3%) showing an unexpected and significant increase. By linking molecular mechanisms with the dynamics of neural circuitry and behavioral states, this approach has the potential to contribute substantially to the development of new therapeutics for the treatment of CNS disorders.

Dataset Information

Miniscope GRIN Lens System for Calcium Imaging of Neuronal Activity from Deep Brain Structures in Behaving Animals.

Publications

Miniscope GRIN Lens System for Calcium Imaging of Neuronal Activity from Deep Brain Structures in Behaving Animals.

Similar Datasets

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