Download Title: Mapping social brain circuit in the mouse brain by serial two

Title: Mapping social brain circuit in the mouse brain by serial two-photon
tomography
Abstract:
Gaining an understanding of the brain regions and circuits that govern behavior
is a central goal of systems neuroscience. Social behavior is one of the
evolutionally conserved core animal behavior and pathological manifestation of
social behavior can lead to several disorders including autism in
humans.Identifying brain circuitry involved in social behavior will lead to better
understanding of how brain process and control this important behavior. One
commonly used approach towards such goal is to use immediate early genes,
which increase their expression transiently upon neuronal activation, to identify
brain regions activated by specific external stimuli. However, conventional
detection methods such as in situ hybridization or immunohistochemistry are
labor intensive and semi-quantiative, thus hard to implement to examine
neuronal activation throughout the entire brain.
In this talk, I will present an unbiased automated method for mapping neuronal
activation in the whole mouse brain at cellular resolution. Our approach is based
on the visualization of the immediate early gene c-fos by serial two-photon (STP)
tomography in transgenic c-fos-GFP mice. STP tomography images the mouse
brain as a series of coronal sections by combining two-photon mosaic imaging
and mechanical sectioning by a built-in vibratome in an automated manner. This
method allows us to examine c-fos-GFP change throughout the entire mouse
brain, which helps us to systematically map out brain areas with increased c-fosGFP
labeling
after
social
behavioral
stimulation.The
STPtomography datasets are further processed by computational methods that
detect the activated GFP-positive neurons, warp their distribution to a reference
brain registered to the Allen Mouse Brain Atlas, identify activated brain regions
by statistical tests, and plot the anatomical connectivity between these
regions. We demonstrate the use of this method for the generation of a social
behavior-evoked brain activation map representing the social brain circuitry in the
mouse. This systematic analysis identified a number of new regions including
agranular insular cortex as well as previously described brain regions activated
during social behavior. These brain regions represent candidate nodes of a
complete circuit to regulate mouse social behavior. This method opens the door
to systematic screening of mouse brain circuits under normal conditions and in
models of human brain disorders.