Exploring the Complexities of the Human Brain

Friday - October 13 2023, 05:53 UTC - 1 year ago

Modern neuroscience offers unprecedented resolution of the human and non-human brain with more than 3,000 cell types. The Human brain is the most complex organ with over 100 Billion neurons, and the research has so far identified over 3,300 cell types which show how the brain functions. The study relies on techniques such as single-cell sequencing and helps in understanding neurological disorders.

When scientists first looked at brain tissue under a microscope, they saw an impenetrable and jumbled mess. Santiago Ramon y Cajal, the father of modern neuroscience, likened the experience to walking into a forest with a hundred billion trees, "looking each day at blurry pieces of a few of those trees entangled with one another, and, after a few years of this, trying to write an illustrated field guide to the forest," according to the authors of The Beautiful Brain, a book about Cajal’s work.

Welcome back to The Checkup. Let’s talk brains.A brain atlas is a 3-D map of the brain. Some brain atlases already exist, but this new suite of papers provides unprecedented resolution of the whole brain for humans and non-human primates. The human brain atlas includes the location and function of more than 3,000 cell types in adult and developing individuals. "This is far and away the most complete description of the human brain at this kind of level, and the first description in many brain regions,"Lein says. But it’s still a first draft.

The human brain is really, really complex. I know, shocker! Thus far, the teams have identified more than 3,300 cell types. And as the resolution gets even higher (that’s what they’re working on now), they’re likely to uncover many more. Efforts to develop an atlas of the mouse brain, which are further along, have identified 5,000 cell types. (For more, check out these preprints: 1 and 2) .

But underneath that complexity are some commonalities. Many regions, for example, share cell types, but they have them in different proportions.

And the location of that complexity is surprising. Neuroscience has focused much of its research on the outer shell of the brain, which is responsible for memory, learning, language, and more. But the majority of cellular diversity is actually in older evolutionary structures deep inside the brain,Lein says.

The classic neuroscience approach to classifying cell types relies on either cell shape–think of star-shaped astrocytes–or the cells’ type of activity–such as fast-spiking interneurons. "These cell atlases capitalize on a new suite of technologies that come from genomics,"Lein says, primarily a technique known as single-cell sequencing.

First, the researchers start with a small piece of frozen brain tissue from a biobank. "You take a tissue, you grind it up, you profile lots of cells to try to make sense of it,"Lein says. They make sense of it by sequencing the cells’ nuclei to look at the genes that are being expressed. "Each cell type has a coherent set of genes that they typically use. And you can measure all these genes and then cluster all the types of cells on the basis of their overall gene expression pattern," Lein says. Then, using imaging data from the donor brain, they can put this functional information where it belongs spatially.

So many ways. But one crucial use is to help understand the basis of brain diseases.A reference human brain atlas that describes a normal or neurotypical brain could help researchers understand depression or schizophrenia or many other kinds of diseases, Lein says. Take Alzheimer’s as an example. You could ap .