Fundamental for the survival of animals in familiar and unfamiliar territories is the representation of surroundings, which requires the use of multiple cognitive capabilities. As a result, beings have adopted numerous behavioral and foraging strategies to explore. Exploration falls into these innate behaviors and represents the act of gathering information from surrounding unknown environments. While navigating through space, the acquisition and consolidation of novel spatial information requires different brain areas to synergistically orchestrate exploratory cognitive processes and, consequently, select defined motor outcomes. Although the involvement of the dorsomedial striatum (DMS) has been implicated as a key structure in orchestrating navigation strategies involved in spatial learning, little is known about its specific role in action selection during navigation through novel and familiar places for self-paced learning. In my current project, I am keen to better understand the role of defined DMS neurons and their afferents in the acquisition of novel spatial maps in freely-moving animals using anatomical, electrophysiological, computational, and imaging approaches. This requires a close examination of multiple brain regions, including the striatum and its inputs, and how these jointly process and execute exploratory actions in unfamiliar environments. To begin with, I will investigate the role of defined DMS neurons during spatial exploration (Aim 1, K99 phase). During this stage, I will also develop optogenetic and electronic circuit tools that will allow me to silence defined DMS neurons (Aim 1, K99 phase) and specific DMS inputs during exploration (further in Aim 3). I will then characterize the role of DMS inputs encoding for place, novelty, and familiarity, as well as their role in spatial learning (Aim 2, K99 phase). The last step will consist of dissecting the synaptic plasticity of afferents to defined striatal neurons shaping action selection during navigation in novel and familiar places and spatial learning (Aim 3, R00 phase). Together, these studies will clarify the neural mechanisms underlying spatial learning and its function in the brain. My principal mentor, Dr. Rui Costa, is a top-notch neuroscientist in the field of neurobiology of actions. As part of the Zuckerman Institute for Brain and Behavior, the Costa lab provides access to the innovative and collaborative scientific environment at Columbia University, making it an ideal place for me to pursue these research aims. The necessary scientific skills will be acquired based on my training plan during the K99 phase, the expertise of my mentors and support platforms to acquire the relevant techniques. The Columbia neuroscience community together with my active participation in data presentations, attendance of seminars, and professional courses will further guide me towards independence. During the R00 independent phase, I aim to further develop my research and analyze the impact of striatal inputs on specific exploratory actions key in developing a detailed spatial map with innovative behavioral, neurophysiological, and computational techniques.
The selection of precise exploratory actions during navigation of unknown and known locations is key for spatial learning. Yet, the neuronal mechanisms regulating action selection in unknown surroundings for the acquisition of new memories remain elusive. My research plan proposes the combination of state-of-the-art neuronal tracing techniques with temporally precise optogenetic manipulation of discrete neuronal circuits and quantitative analyses of neuronal activity in freely-moving mice.
