CRCNS: Emergence of Coordinated Multi-Region Brain Activity Supporting Behavior

Changes in interactions between neurons enable diverse computations and flexible behaviors. Such
changes can occur very rapidly by rerouting information flow through existing connections, or more slowly
by updating connections. The proposed project will study how local and brain-wide dynamics arise during
learning of goal-directed behaviors. Experiments will use novel ‘all-optical’ experimental techniques to
causally map network interactions at cellular resolution in combination with data-constrained computational
models, to follow the learning process in the living brain with unprecedented detail. The investigation will
focus on learning mechanisms in several novel memory-guided behavioral tasks, that either do not require
learning, or specifically tailored for studying learning within and over days. This will fundamentally advance
the understanding of how different learning mechanisms shape brain-dynamics and behavior.
Aim 1: Mapping changes in causal interactions (effective connectivity) between neurons in local cortical
circuits. Modeling and experiments will allow disentangling contributions of synaptic plasticity and gating to
changes in network interactions and representations during learning.
Aim 2: Investigating unique properties of cortex-wide neural activity. Preliminary work, based on cellular-resolution mesoscopic imaging of ~1,000,000 neurons, led to the discovery that spatial and temporal scales
of brain-wide dynamics follow a power-law. Intriguingly, the most dominant modes of activity are global and
fast, differently from any existing network model. The proposed work will uncover biological mechanisms
supporting the emergence of these newly discovered cortical states during learning.
Aim 3: Investigating functional implications of learned neural network dynamics studied in Aims 1 and 2. To
test the hypothesis that such dynamics enable animals to perform flexible memory-guided behaviors, work
will focus on modeling the effect of targeted optogenetic perturbations of neural activity on different spatial
scales on network dynamics and behavior.
Overall, the proposed collaborative study will leverage the PIs complementary expertise, to deepen the
understanding of mechanisms and function of neural dynamics on different spatial scales. The
experimental and theoretical methods developed as part of this proposal will provide insight for brain-wide
control of memory-guided behavior, and will serve as a road-map for future studies of other behaviors
controlled by distributed brain networks.

Grant Number: 5R01NS135853-03
NIH Institute/Center: NIH
Principal Investigator: Johnatan Aljadeff