# Impact of Sleep and Corticostriatal Functional Connectivity on Behavioral Flexibility

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $40,018

## Abstract

PROJECT SUMMARY
A large body of work has revealed how motor cortex (M1) drives the refinement of emergent motor skills towards
precise, automatic actions. Moreover, our lab’s findings implicate the emergence of corticostriatal (CS) functional
connectivity between M1 and dorsolateral striatum (DLS) as essential to refinement of skills that involve both
gross and fine motor movements, such as a skilled reach-to-grasp (RTG) task where rats execute precise
reaches to retrieve reward pellets. However, while much is known about the evolution of M1/DLS activity
towards predictable behavior output, little is known about how the motor system responds to large
errors by allowing flexible adaptation of learnt skill through behavioral exploration.
Here we use a new variant of the RTG task (where rats first learn reaching to one location before the pellet
holder is moved to a non-overlapping position, termed ‘re-aiming’ task hereafter) to probe how the CS network
enables behavioral flexibility in response to environmental changes. Our preliminary data shows that while rats
eventually “re-aim” to the new pellet location, the process occurs only across days, rather than within day, and
involves a transitory state of heightened motor variability. This suggests that “offline” consolidation during sleep
plays a key role in mediating the balance between behavioral stability vs exploration, and the central hypothesis
of this proposal is that non-rapid eye movement (NREM) sleep bidirectionally modulates CS connectivity
to enable behavioral exploration.
Here we use an interdisciplinary approach of exploratory data analysis, computational modeling, and causal
manipulations to answer the above question. In Aim 1, we will assess how the temporal nesting of sleep spindles
with slow oscillations and delta-waves modulates both behavioral switchover and theta frequency LFP coherence
during reaching (the emergence of which has been shown to track with successful reaching behavior). In Aim 2,
we will fit spiking data with a cross-area computational model to dissociate the dynamics of M1 vs DLS activity
across the re-aiming paradigm to gain deeper insight into each region’s respective contributions to behavioral
stability vs flexibility. And lastly in Aim 3, we will use closed-loop optogenetics to causally determine the
contributions of sleep spindles to both behavioral stability and CS functional connectivity. Together, these
experiments will further our understanding of sleep physiology as it relates to behavioral flexibility and lay a
strong foundation towards sleep-based interventions for motor disorders after injury, stroke, and perhaps even
mental health disorders (such as addiction or obsessive-compulsive disorder) that prominently implicate
corticostriatal connectivity.

## Key facts

- **NIH application ID:** 10463506
- **Project number:** 1F31NS127514-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** David Darevsky
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $40,018
- **Award type:** 1
- **Project period:** 2022-05-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10463506

## Citation

> US National Institutes of Health, RePORTER application 10463506, Impact of Sleep and Corticostriatal Functional Connectivity on Behavioral Flexibility (1F31NS127514-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10463506. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*