Experience-driven development of reliable stimulus representations in dynamic cortical networks

Project Summary/Abstract The onset of sensory experience transforms immature cortical networks into mature representations that support reliable discrimination of behaviorally relevant stimuli. Cortical responses encode stimuli by the profile of activity across a population of neurons (population response). To provide stimulus information, population responses must be different across stimuli and also reliable across presentations of the same stimulus. Novel techniques that measure activity chronically across large neuronal populations with single-trial resolution in developing animals will now help us define how reliable population responses mature with experience. This question is fundamental as a reliable transmission of information is critical for perception and cognition. The candidate’s previous work shows that a developmental alignment between the structure of feedforward inputs and recurrent connectivity in superficial layers 2/3 of the ferret primary visual cortex (V1) contributes to the emergence of a reliable representation of edge orientation following the onset of visual experience. During the K99 period, the candidate will expand on these initial findings addressing two key questions. First, the candidate will use novel methods he has designed for 3-dimensional electrode array recordings in developing ferrets to resolve the sequence of changes in response properties and connectivity across layers 2/3 and layer 4, the main source of feedforward inputs to layers 2/3, that result in feedforward-recurrent alignment after experience. Second, the candidate will use chronic two-photon imaging to resolve if the maturation of inhibitory responses in layers 2/3 contributes to increase population response reliability in this layer. To achieve these goals, the candidate will be mentored by Dr. David Fitzpatrick, a world-renowned authority on vision development and an expert in imaging techniques. Through collaborations with Dr. Ting at the Allen Institute and Dr. Yasuda at the Max Planck Florida Institute for Neuroscience (MPFI), the candidate will develop novel genetic constructs to disrupt activity- dependent plasticity in specific cortical layers or neuronal types in ferret V1. As an independent investigator, the candidate will use these tools to investigate how sensory experience refines cortical circuits to produce a mature representation at the neuronal population level. As a first step towards this novel scientific direction, the candidate will consult with Dr. Inagaki at MPFI to resolve whether experience-driven synaptic plasticity in layer 4 is necessary for the emergence of reliable population responses in layers 2/3. This methodological approach differentiates the candidate’s research from Dr. Fitzpatrick’s, which focuses on single-cell synaptic architecture and response properties. To acquire the professional skills essential for a successful transition to independence, the candidate will consult with Dr. Namboodiri, who will guide the candidate’s plan for training in professional development, fostering his success as a young investigator. Throughout the project period, the mentor, collaborators, and consultants will work together as an advisory committee to guide the candidate as he improves his research, secures an independent research position, and establishes a successful lab at his new institution.