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.
