# Circadian Control of the VTA: Neural and BBB Dynamics

> **NIH NIH F32** · BROWN UNIVERSITY · 2024 · $73,828

## Abstract

PROJECT SUMMARY
Making correct choices, and learning from them, requires a detailed understanding of biological needs. Such
needs are governed by fluctuating drives (hunger, thirst) and by larger, underlying rhythms such as the Circadian
Cycle. Forebrain circuits, and axonal inputs to them from the Ventral Tegmental Area (VTA), are crucial to
computations underlying choice and learning. A key source of body state information for the Forebrain are
circulating signals in the vasculature. However, the blood-brain barrier (BBB) is commonly reported to block
almost all such signaling molecules to protect the brain from contamination. Our lab has been testing a potential
resolution to this tension: Specifically, we have found that BBB permeability is dynamic, only ‘opening’ at
behaviorally-relevant moments when the risk of contamination is worth the reward of higher quality state
information. Our extensive Preliminary Data show that BBB permeability events occur in response to local VTA
axon activity both endogenous and optogenetically-driven.
I build on these new findings and my graduate studies, where I discovered substantial vascular dynamics
between sleep and waking (Turner et al., 2020)1 and how these relate to indicators of arousal (Turner et al.,
2023)2. In Aim I, I will test the hypothesis that VTA axon activity and local dopaminergic (DA) levels peak
early in the active (dark) phase, and then decrease progressively. I will test this hypothesis with 1P and 2P
imaging of VTA axon activity and DA signaling in Neocortex and Striatum, leveraging behavioral paradigms
shown to drive distinct patterns of VTA axon activity (Hamid et al., 2021)3. In Aim II, I will test the hypothesis
that VTA-driven BBB permeability events show the same relationship to Circadian Cycle. Specifically, that
single axon spikes and optogenetic input drive larger amplitude permeability events early in the active (dark)
phase followed by a decreased relative impact across this phase. In these studies, I will test endogenous and
optogenetic-driven VTA axon activation while imaging local BBB permeability events and systematically testing
that VTA-driven BBB permeability events allow the transmission of multiple active signaling molecules including
sex hormones and metabolic cues. In Aim III, I will test the hypothesis that integration of prior reward
history will have the strongest impact early in the active (dark) phase. In these studies, I will employ a two-
armed bandit task in conjunction with fiber photometry recordings of DA levels in SI, mFC, DS, and NAc. I will fit
this data into behavioral computation frameworks developed in my co-sponsor Dr. Michael Frank’s laboratory.
These studies will generate unique data that tests how a major determinant of behavioral state, the Circadian
Cycle, relates to VTA axon activity, rapid changes in BBB permeability, and behavior itself. Further, these
studies are ideal for my training, directly supporting my central career goal of unders...

## Key facts

- **NIH application ID:** 10947727
- **Project number:** 1F32NS134617-01A1
- **Recipient organization:** BROWN UNIVERSITY
- **Principal Investigator:** Kevin Lawrence Turner
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $73,828
- **Award type:** 1
- **Project period:** 2024-07-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10947727

## Citation

> US National Institutes of Health, RePORTER application 10947727, Circadian Control of the VTA: Neural and BBB Dynamics (1F32NS134617-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10947727. Licensed CC0.

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