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The mesoscale challenge in brain mapping

Microscale

Microscale

Single neurons
Microscale

Mesoscale

Brain circuits
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Macroscale

Brain regions

Traditional neurotechnologies limit researchers to mapping brain activity either in fine detail but in very few neurons at a time (microscale), or in large regions (macroscale) but without the detail of their individual neurons.

To truly understand how the brain computes the mind, we need technologies that can map activity in its circuits and networks at the mesoscale, i.e in thousands of individual neurons simultaneously during a cognitive or behavioral task. Enter Inscopix. 

Inscopix miniature microscope:
The world's smallest brain observatory

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The innovation at the core of the Inscopix brain-mapping platform is the integration and miniaturization of the bulky bench-top fluorescence microscope (Left) into a 2 gm device (Right), smaller than a fingertip, that can be mounted onto the skull of a living animal subject to observe its brain activity.

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How the miniature microscope works

  1. Neurons of interest are genetically modified to express GCaMP6, a biological sensor of neural activity.

  2. A GRIN lens, essentially a glass needle, is then surgically implanted through the skull (not shown) and brain tissue to enable optical access to the GCaMP6-expressing neurons.

  3. Next, a baseplate is installed on the skull to serve as a docking site for the miniature microscope.

  4. Finally, the miniature microscope is installed onto the base plate to interface with the optical needle.

When a neuron is activated, calcium levels increase inside the cell. GCaMP6 binds to the calcium and reports the event by producing a transient fluorescent signal. The miniature microscope captures the changes in fluorescence and transmits high-resolution images through a flexible cable and data acquisition (DAQ) box to a computer (see below).

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The miniature microscope in action

Imaging the thinking, working brain (Right) of a freely behaving mouse (Left). The miniature microscope enables cellular resolution and cell-type specific GCaMP6 imaging in ~1,200 excitatory CA1 hippocampal neurons during active behavior over months.
Courtesy: Schnitzer Lab, Stanford

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The technology stack

The Inscopix miniature microscope is part of our end-to-end integrated technology stack that empowers researchers to catalyze ground-breaking neuroscientific discoveries with speed and scientific rigor.

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Biological Reagents

Our ready-to-image biological reagents, GCaMP6 carrying viruses, enable researchers to hit the ground running with nVista and nVoke.
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Instrumentation

The miniature microscope is the foundational technology for our nVista (activity imaging) and nVoke (activity imaging and manipulation) products.
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Neuroinformatics

Our Mosaic software helps researchers to derive insights from nVista and nVoke experiments faster by converting video datasets into activity traces.

See more science enabled by Inscopix

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