Summary: UCLA researchers reveal the amygdala has much greater cell diversity than previously believed.
UCLA researchers have shown for the first time a comprehensive picture of cell diversity in the amygdala, a vital brain region involved in the regulation of emotions and social behavior, as well as in autism spectrum disorders, depression and other mental disorders. As part of the study, the team also reported on a new method for systematically linking the distinct types of brain cells to specific behavioral functions.
“The level of diversity of cells within the brain has not been well understood,” said study senior author Weizhe Hong, assistant professor of biological chemistry and neurobiology at the David Geffen School of Medicine at UCLA. “By revealing the many types of cells in the amygdala and then developing a method for studying the functional role of these cells, our findings can pave the way to unraveling some of the mysteries in how this important part of the brain works and what goes wrong in mental health disorders.”
The findings are published in the October 11 issue of the journal Neuron.
Unlike other organs in the body, the brain is known to consist of highly heterogeneous types of cells — a heterogeneity that is at the root of cognitive functions such as learning, memory, emotional arousal and decision-making, as well as brain disorders. Using recently developed sequencing technology that allows researchers to conduct rapid analyses of individual cells, the UCLA group found that the amygdala has much greater cellular diversity than previously known — featuring 16 types of neurons and many types of non-neuronal cells.
Describing the diversity of cells within the amygdala was only a first step. “Once we know these different cell types, we want to understand how distinct types of brain cells are linked to behavioral functions and disease conditions,” Hong said. “In the past, there was no systematic way of doing this.”
Hong and colleagues overcame a long-standing technical hurdle to develop a method, called Act-seq, for systematically linking brain-cell types to behavioral functions. Using the new method, they pinpointed two of the 16 neuronal types in the amygdala as being involved in stress-related behaviors. The new method also facilitates the study of acute molecular and cellular changes in the brain in injury and disease. For example, the researchers found a substantial activation of glial cells, a type of supporting cells in the brain, immediately after a seizure.
The team is continuing to use the new research tool to investigate how the amygdala controls emotional and social behaviors, as well as how this goes wrong in mental disorders, such as autism spectrum disorders and depression. “We expect to learn a great deal by breaking down the amygdala’s individual components and their functions,” Hong said.
In addition to Hong, study authors are Ye Emily Wu, Lin Pan and Yanning Zuo of the departments of biological chemistry and neurobiology at UCLA, and Xinmin Li of the department of pathology at UCLA.
Source: David Olmos – UCLA
Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: Abstract for “Detecting Activated Cell Populations Using Single-Cell RNA-Seq” by Ye Emily Wu, Lin Pan, Yanning Zuo, Xinmin Li, and Weizhe Hong in Neuron. Published online October 11 2017 doi:10.1016/j.neuron.2017.09.026
Detecting Activated Cell Populations Using Single-Cell RNA-Seq
•Act-seq minimizes artificial transcriptional changes during tissue dissociation
•Act-seq enables unbiased characterization of cell types and their acute activation
•Application of Act-seq provides the first molecular taxonomy in the amygdala
•Application of Act-seq identifies neuronal subpopulations activated by stress
Single-cell RNA sequencing offers a promising opportunity for probing cell types mediating specific behavioral functions and the underlying molecular programs. However, this has been hampered by a long-standing issue in transcriptional profiling of dissociated cells, specifically the transcriptional perturbations that are artificially induced during conventional whole-cell dissociation procedures. Here, we develop Act-seq, which minimizes artificially induced transcriptional perturbations and allows for faithful detection of both baseline transcriptional profiles and acute transcriptional changes elicited by behavior/experience-driven activity. Using Act-seq, we provide the first detailed molecular taxonomy of distinct cell types in the amygdala. We further show that Act-seq robustly detects seizure-induced acute gene expression changes in multiple cell types, revealing cell-type-specific activation profiles. Furthermore, we find that acute stress preferentially activates neuronal subpopulations that express the neuropeptide gene Cck. Act-seq opens the way for linking physiological stimuli with acute transcriptional dynamics in specific cell types in diverse complex tissues.
“Detecting Activated Cell Populations Using Single-Cell RNA-Seq” by Ye Emily Wu, Lin Pan, Yanning Zuo, Xinmin Li, and Weizhe Hong in Neuron. Published online October 11 2017 doi:10.1016/j.neuron.2017.09.026