# THE ROLE OF MEDIUM SPINY NEURONS IN SLEEP DEPRIVATION-INDUCED COGNITIVE RIGIDITY.

> **NIH NIH R21** · WASHINGTON STATE UNIVERSITY · 2024 · $191,250

## Abstract

ABSTRACT
This project is focused on understanding the mechanisms behind performance deficits that occur with
insufficient sleep. In particular, studies in humans have identified cognitive rigidity (compromised situational
adaptability in decision making) as a consequence of sleep deprivation (SD). Cognitive rigidity is influenced by
a striatopallidal brain circuit that is conserved in subhuman primates and rodents and involves a cell type that
expresses dopamine-type 2 (DrD2) and adenosine-type 2a (A2a) receptors. In the current studies, we will
employ mouse electrophysiology recordings and real-time striatal event imaging, in addition to a rat cognitive
flexibility task that is susceptible to SD. We will apply these techniques to transgenic mouse and rat models in
order to interrogate the role of the DrD2/A2a striatopallidal brain circuit in mediating the effects of SD at the
biochemical, receptor, regional (brain structure and electrophysiology) levels in addition to probing complex
whole organism behavior. In Aim 1, we will determine the extent to which DrD2 cell membrane localization and
intracellular cyclic adenosine monophosphate concentration ([cAMP]i) in striatal medium spiny neurons vary as
a function of spontaneous and SD-induced sleep/wake cycles. This experiment will address our dynamic
interplay hypothesis that striatal DrD2 receptor availability and the inversely-related [cAMP]i function as cellular
mediators of sleep pressure in the striatum. In Aim 2, we will examine whether the activity of striatal DrD2/A2a
cells is necessary and sufficient to confer the negative impacts of SD on cognitive flexibility. We predict that
cell-type specific chemogenetic activation or inactivation of these neurons will mimic or rescue, respectively,
the behavioral consequences of SD in a touchscreen operant reversal task. The anticipated results of this
project will confirm the mechanistic role of the striatopallidal medium spiny neuron population in the
performance decrements that stem from sleep loss. Here, our focus is on dopaminergic signaling, but our
long-term objective is to elucidate how signaling mechanisms in the striatum and connected brain areas
converge to regulate the cognitive processes that are compromised by SD. Overall, this work will set the stage
for future inquiries by confirming cell type-specific SD mitigation targets in striatal circuitry. It will also inform
the public and scientific constituencies of potential mechanistic and compensatory approaches to
reversing/preventing the deleterious effects of sleep loss.

## Key facts

- **NIH application ID:** 10791860
- **Project number:** 5R21NS132116-02
- **Recipient organization:** WASHINGTON STATE UNIVERSITY
- **Principal Investigator:** Christopher John Davis
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $191,250
- **Award type:** 5
- **Project period:** 2023-03-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10791860

## Citation

> US National Institutes of Health, RePORTER application 10791860, THE ROLE OF MEDIUM SPINY NEURONS IN SLEEP DEPRIVATION-INDUCED COGNITIVE RIGIDITY. (5R21NS132116-02). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10791860. Licensed CC0.

---

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