A multimodal platform to bridge the experimental gap between behavioral, neuronal, and molecular studies

点击翻译按钮获取中文摘要

ABSTRACT Depicting the specific neuronal identity and connectivity underlying particular brain function remains a central goal for neuroscience. For over a century, neuroanatomy has continued to play critical roles in referencing a neuron's synaptic contact, dendritic morphology and axonal projection to its connectivity. The advances of genetic probes, optical imaging modalities and computer technologies permit monitoring and manipulating neuronal activity in living animals with unprecedented precision and scale. In addition, the forefront of “-omics” study begins to discriminate the molecular diversity of the heterogenous population neurons in the same brain region. The identification of unique molecular markers further enables creating novel transgenic models to interrogate precise subsets of neurons. Despite the tremendous success in applying these revolutionary technologies in studying systems and behavior neuroscience, there currently lacks a unified experimental paradigm to directly link activity, connection and molecular information of the exact same neurons in a functional circuit at the single cell/single synapse resolution. The ability to do so will remove the ambiguity in current attempts to correlate different attributes of the “same” neuronal populations sampled from different animals. More importantly, the ability to do so will tremendously improve our efficiency and accuracy in differentiating specific neuronal populations that correlate with distinct circuit functions in the same brain region. Here, we demonstrate the feasibility of coMAAP, a multimodal experimental paradigm that allows correlative optical mapping of activity, anatomy and molecular-identity of the same neurons in the same animal. Importantly, coMAAP can be implemented using standard instruments. While combining with specialized imaging modalities it can achieve unprecedented resolution and scale. The goals of our proposal are to optimize and validate the coMAAP experimental paradigm, and to utilize coMAAP to depict the heterogenous neuronal populations that are arousal activated in the mouse ventral tegmental area (VTA).