Patterns of Spontaneous Activity in the Assembly and Rewiring of Functional Sensory Circuits

Introduction

It is commonly held that spontaneous activity in the immature brain prepares the neural circuits to process sensory information at the onset of experience. The best studied patterns of such activity are those observed postnatally in rodents, during stages that resemble the last months of gestation in humans.

Research Gap

However, the features and functions of spontaneous activity at earlier stages, when the brain’s foundations are laid down and cortical areal identities are acquired, remain largely unknown.

Research Proposal

Here, I propose to develop an extensive and creative research program aimed at understanding the role of the patterns of spontaneous activity in the specification of sensory cortices and long-term plasticity. This novel line of research is founded on strong preliminary results and pursues the hypothesis that different cortical sensory territories exhibit unique patterns of spontaneous activity that interact with emerging area-specific transcriptional programs to specify sensory areas functionally.

Methodology

1. Extraction of Patterns: We will first extract the earliest patterns of spontaneous activity from cortical and subcortical territories in embryonic and perinatal mice in vivo and study their concurrent spatiotemporal genetic signatures by single-cell transcriptomics.

2. Perturbation of Activity Patterns: Next, we will perturb these early activity patterns within a specific sensory modality to reveal if such perturbation modifies the genetic landscape and affects sensory identity.

3. Evaluation of Behavioral Consequences: Finally, we will evaluate the behavioural consequences of functional cortical re-specification in adult mice.

Significance

SPONTSENSE will set the stage to understand the principles of sensory circuit development and shed new light on brain plasticity following sensory defects. I envisage that this information will pave the way to devise strategies that may serve to direct these programs of plasticity in clinical situations when sensory input has been compromised.