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DISEASE & THERAPEUTICS

Developing CNS therapeutics rooted in disease mechanisms

The Inscopix miniature microscope platform enables researchers to monitor and manipulate circuit pathophysiology over long periods of time in animal models of diverse neurological and psychiatric disorders. This provides an objective and quantitative measure for investigating disease and therapy induced changes directly in the brain.

Deeper insights into circuit pathophysiology

nVista imaging of calcium dynamics in striatal D1- or D2-Medium Spiny Neurons of 5 mice. Credit: Dr. Jones Parker, Stanford/Pfizer

  • Dissect the role of specific cell-types and brain circuits in disease etiology and therapeutic intervention

  • Derive mechanistic insights into disease progression and therapeutic action

  • Discover predictive and pathological circuit activity-based biomarkers of brain disorders

  • Identify promising therapeutic targets from functionally defined cell-types

  • Conduct in vivo drug screening assays in a high-throughput fashion

 

RESEARCH HIGHLIGHT

Neural activity signatures in Parkinson's disease

 

Researchers from Stanford & Pfizer used state-of-the-art brain imaging technology, our miniature microscope-based platform nVista, to peer into a brain region called the striatum in a mouse model of Parkinson’s disease (PD). By monitoring activity in hundreds of neurons simultaneously in the living brain, they observed aberrations in striatal activity patterns that encode voluntary movement. The researchers then tested compounds like L-DOPA, the mainstay PD treatment, and other dopamine agonists that have proven to be less efficacious than L-DOPA in the clinic, and found significant correspondence between a compound's ability to correct the pathological striatal activity patterns and its clinical efficacy.
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RESEARCH HIGHLIGHT

Measuring the effects of the ambient Zolpidem directly in the brain

There have been growing concerns about the adverse effects of the ambient Zolpidem on cognition and memory. In this collaboration between Johnson & Johnson and Inscopix, scientists tracked  large-scale calcium dynamics in the hippocampus (a brain region critical for memory) of Zolpidem-administered mice. They discovered that the majority of the hippocampal neurons decreased their rate of calcium transients upon receiving Zolpidem, a potential explanation for the amnesia observed in humans.

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RESEARCH HIGHLIGHT

Predicting convulsive epileptic seizures from pathological calcium activity in the hippocampus

Seizure activity has traditionally been assessed with behavioral monitoring and whole-brain EEG recording. By combining these methods with nVista calcium imaging in mice treated with the proconvulsant kainic acid (KA), Johnson & Johnson and Inscopix scientists discovered aberrant calcium dynamics in hippocampal neurons before the onset of behavioral and EEG signatures of convulsive motor seizures. These activity-based signatures signaling an imminent convulsive seizure open up the possibility for pre-emptive therapeutic intervention to mitigate excitotoxic damage to the hippocampus.

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RESEARCH HIGHLIGHT

Identifying druggable targets from functional imaging of anxiogenic neural circuits

At the DECODE Summit (2016), Dr. Garret Stuber (UNC) shared how circuit-level insights can be applied to the development of highly selective drugs. Dr. Stuber used nVista imaging to hone in on a small subset of BNST GABAergic neurons, defined by their expression of the Nociceptingene. These neurons uniformly exhibited enhanced activity as the mouse transitioned to anxiogenic environments. Through single-cell transcriptomic analysis of this Nociceptin+ subpopulation, Dr. Stuber hopes to identify other uniquely expressed genes, potential targets for cell-type specific pharamacological intervention for anxiety disorders.

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