# Identify the schemata by which subcortical signals influence frontal cortical dynamics and cognitive behaviors

> **NIH NIH U19** · ALLEN INSTITUTE · 2022 · $528,341

## Abstract

Summary, Project 4 (Identify the schemata by which subcortical signals influence
frontal cortical dynamics and cognitive behaviors)
This research project is focused on dynamic interactions between subcortical areas and frontal cortex via
thalamus during flexible behavior. Frontal cortex, including motor cortex and medical prefrontal cortex, displays
complex patterns of neural activity that correlate with behavior. These patterns can be decomposed into activity
modes (i.e. subspaces in activity space), such as the persistent activity correlated with short-term memory, and
the rapidly modulated activity associated with voluntary movements. Complex behaviors correspond to
sequences of cortical activity modes. Frontal cortex is tightly coupled with higher-order (non-sensory) thalamus
to mediate behavior. Thalamus in turn receives driving input from the basal ganglia the and other subcortical
structures. We test the hypothesis that different subcortex inputs to specific thalamic regions control different
aspects of cortical activity, including setting the time periods when short-term memories are maintained, the
transitions from motor planning to movement execution (Aim 1), and updating and maintaining the values of
specific actions during foraging. Our modeling framework (Overall, Project 5) links the dynamical systems
perspective of neural computation with actual multi-regional neural circuits and makes predictions that can be
tested with neurophysiology.
We employ two behavioral tasks in mice that engage well-defined but distinct cortical activity modes. In a
memory-guided response task, neurons in the anterior lateral motor cortex (ALM) show preparatory activity,
which predicts specific future movements. Just before the onset of movement, preparatory activity collapses in
favor of activity modes that drive movement. In a dynamic foraging task, neurons in the medial prefrontal cortex
(mPFC) show slowly varying activity patterns that correlate with the value of one action compared to another.
This activity is updated based on new information, such as the size of a reward. Projects 1 - 3 provide information
about the circuits linking subcortical areas, thalamus, and ALM / mPFC. Building on these circuit mapping
experiments we will perform simultaneous recordings from connected subcortex → thalamus → cortex circuits
using new multi-shank Neuropixels probes with 5120 recording sites (Project 3). We will combine these
recordings with optogenetic manipulations of subcortex and modern multi-variate analysis methods (Data
Science Core) to track how subcortical signals propagate through the thalamus into cortex. In the memory-guided
response task we will probe the role of the substantia nigra reticulata, acting via the ventromedial nucleus, on
maintenance of movement planning, and the impact of midbrain movement centers (e.g. pedunculopontine
nucleus), acting via the posterior mediodorsal nucleus, on switching from movement planning to movement
initiation (...

## Key facts

- **NIH application ID:** 10294404
- **Project number:** 1U19NS123714-01
- **Recipient organization:** ALLEN INSTITUTE
- **Principal Investigator:** Karel Svoboda
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $528,341
- **Award type:** 1
- **Project period:** 2022-01-15 → 2026-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10294404

## Citation

> US National Institutes of Health, RePORTER application 10294404, Identify the schemata by which subcortical signals influence frontal cortical dynamics and cognitive behaviors (1U19NS123714-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10294404. Licensed CC0.

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