Our brains are made up of a confusing tangle of hundreds of different kinds of cells, wired together in an even larger number of different combinations.

While scientists are making headway at sorting out the number and types of neurons and other cells that are the building blocks of the mammalian brain, broader questions remain largely unanswered: Why do we have so many kinds of neurons? What do they all do?

A new study led by researchers at Boston University in collaboration with scientists at the Allen Institute for Brain Science, a division of the Allen Institute, describes a method aimed at addressing those questions. The study, published Friday in the journal Science, also pinpoints new functions for one kind of mouse neuron that’s involved in sensing touch.

While techniques exist to capture the activity of individual neurons in the brain, scientists usually know very little about what type of neuron they’re watching. The new method, developed by Jerry Chen, Ph.D., an assistant professor of biology at Boston University, uses Allen Institute catalogs of brain cell types married with a technique to study the neural activity of those specific types.

The catalogs of brain cell types were generated by measuring the full suite of genes switched on in a single cell and then cataloging the cell types based on this measure of gene activity, also called single-cell transcriptomics. Chen and his colleagues used a subset of these genes together with another technique that measures neurons’ activity under the microscope as animals are performing different tasks to link neuron types with their function. The project grew from Chen’s experience as an Allen Institute Next Generation Leader, an advisory council at the Institute comprised of early-career neuroscientists.

“The field is absolutely ready for these kinds of data,” said Bosiljka Tasic, Ph.D., Director of Molecular Genetics at the Allen Institute for Brain Science and one of the study co-authors. “We have cell types that we define based on these molecular signatures, and now we want to know what they do.”

Neurons tuned to important sensations

Chen and his team used the technique to examine neurons in a part of the brain that respond to and process touch. Using laboratory mice that were trained to respond to their whiskers being touched in a certain way, the scientists looked for neural activity that correlated to specific kinds of touch. They found that one neuron type, named Baz1a based on a gene it expresses, seems to act as a kind of coordinating hub for neural circuits related to touch and memory.

“Let’s say you’re rummaging through your bag feeling for your car keys with your fingers. You know what you’re looking for, because you’ve learned what a car key feels like, so there are certain features that will probably jump out at you,” Chen said. “I think that’s what these Baz1a cells are doing. If anything salient is perceived, those cells are activated and they recruit the rest of the network to start to fill in the gaps and process information.”

They also found that Baz1a neurons have persistent expression of genes associated with plasticity, or the brain’s ability to adapt in response to new information and memory, meaning these cells might be primed to remember old sensory information while accommodating new details. The Boston University team is now looking through the Allen Institute datasets for other neuron types that have similar genetic features to understand whether cells with plasticity genes persistently switched on might play a general role in learning and memory.

The research described in this article was partially funded by award U19MH114830 from the National Institutes of Health’s National Institute of Mental Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of NIH and its subsidiary institutes.