PROJECT SUMMARY/ABSTRACT It is estimated that the human brain contains an overwhelming 1015 synapses, structures essential for the normal functioning of neural circuits. Our knowledge of the connections that form these critical signaling sites, in even the simplest vertebrate nervous systems, is sorely lacking.
Project Summary Developing new methodological and analytical tools to address currently insurmountable experimental questions is crucial to the future of neuroscience. While recent advances in two-photon microscopy and activity sensors have revolutionized our understanding of the cellular and circuit basis of behavior, many barriers still exist that preclude fully exploring the molecular basis of these processes in vivo.
Project Summary Population neuroscience requires investigation of brain-behavioral relationships within epidemiological samples studied in longitudinal designs, including a large number of assessment modalities and with subjects enrolled at many data collection sites to achieve a large sample and broad representation of the population.
SUMMARY/ABSTRACT A major goal of neuroscience is to understand how neuromodulatory systems regulate core processes of brain and behavior, from motor function and learning to reward, aversion, attention, and sleep. These systems go awry in schizophrenia and disorders of mood, motor control and cognition. Treatment for these conditions often turns to pharmacological manipulation of neuromodulators and their receptors. Understanding of neuromodulatory circuits has advanced considerably thanks to optogenetics and chemogenetics. But neuromodulation is difficult to crack.
Abstract While current efforts in the analysis of neural circuits focus on interneuronal connectivity mediated by chemical synapses, less is known about the contribution of electrical synapses. Electrical transmission is mediated by neuronal gap junctions, which are widely distributed throughout the vertebrate brain.
Project Summary New tools are urgently needed to selectively target constructs that monitor and manipulate the activity of individual cell types without having to rely on genetic manipulation.
PROJECT SUMMARY Overview: We will extend and develop implementations of foundational methods for analyzing populations of attributed connectomes. Our toolbox will enable brain scientists to (1) infer latent structure from individual connectomes, (2) identify meaningful clusters among populations of connectomes, and (3) detect relationships between connectomes and multivariate phenotypes. The methods we develop and extend will naturally overcome the challenges inherent in connectomics: high-dimensional non-Euclidean data with multi-level nonlinear interactions.
The goal of this research is to establish new robust methods for manipulation of specific circuits and genetically defined neuron types in brains of model organisms with small molecules. While several chemical-genetic techniques are already available, these techniques have drawbacks that limit their utility.
There is an increasing need for efficient and robust software to process, integrate, and offer insight across the diversity of population imaging efforts underway across the BRAIN Initiative and other projects.
