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Faculty Collaborations

Researchers Develop New Tool to See How Different Brain Cell Types Work Together

“By making these previously hidden interactions visible, we hope to inform future treatments that target the root causes of dysfunction in circuits of the brain rather than simply addressing symptoms.”

When probes are inserted into the brain for research or clinical purposes, the electrical activity of neurons is recorded. These signals can be used to understand how the brain performs certain computations or even to identify pathological states. However, brains are composed of cell types that perform different roles in computation and are differentially affected by certain psychiatric disorders or drugs. Without a deep understanding of how cell types orchestrate the overall activity patterns, we cannot develop the next generation of therapies.

Researchers from Boston University’s Chobanian & Avedisian School of Medicine, College of Arts & Sciences, College of Engineering and Faculty of Computing & Data Sciences have developed a tool called PhysMAP to separate the “voices” of individual cell types within a crowd of electrical noise by combining several complementary features of each type’s electrical signature. This machine learning algorithm could open up the study of how cell types shape both the healthy computations and the pathological states that electrical recordings have long been able to detect but never fully understood.

“While a variety of disorders can be understood via overall activity alone, a growing number of psychiatric disorders are being recognized as arising from the perturbed interactions between specific cell types rather than changes in overall activity. These so-called “circuitopathies” include human diseases such as schizophrenia, major depressive disorder, and some forms of epilepsy. PhysMAP would allow for the study of interacting cell types in both intact and altered neural circuits, many implicated in the above disorders, in expanded in vivo research settings and perhaps even clinical ones,” explains corresponding author Chandramouli (Chand) Chandrasekaran, PhD, assistant professor of anatomy & neurobiology and psychological and brain sciences at BU.

The researchers used seven open datasets that contained both the electrical activity of single neurons and their cell type identities. In these experiments, scientists combined molecular engineering with optical tools to tie electrical activity to specific cell types with a technique called “optotagging;” and released these datasets when their papers were published. The BU team used these datasets to train PhysMAP to learn the unique electrical signatures of different cell types and verify that this mapping was accurate and better than or comparable to other tools. Crucially, once learned, this mapping could be applied to new datasets where optotagging was not available, enabling the simultaneous study of multiple cell types. This work also illustrates the power of open data sharing. By making their datasets publicly available, scientists enabled the development and validation of entirely new tools without requiring additional experiments.

According to the researchers, the ability to study cell types in vivo—without the requirement of genetic manipulation—would allow the study of how psychiatric disorders arise from circuit dysfunction. “If these cell types can be identified in research settings in the healthy brain, information about their dysfunction can be used to inform the development of future therapeutic strategies,” adds Chandrasekaran.

If these cell types can be identified in research settings in the healthy brain, information about their dysfunction can be used to inform the development of future therapeutic strategies.

Chand Chandrasekaran, PhD

A previous version of this tool (WaveMAP), was deployed to identify cell types in the very first human recordings with Neuropixels (a type of high-density electrode now considered the standard in neuroscience). PhysMAP is more powerful and can be used to identify several of the specific cell types implicated in psychiatric disorders: parvalbumin-positive cells in schizophrenia or Dravet syndrome and somatostatin-positive cells in major depressive disorder. These findings appear online in the journal Nature Communications