# Circuit-Specific Interrogation of the Primate Claustrum

> **NIH NIH F31** · DUKE UNIVERSITY · 2024 · $41,436

## Abstract

PROJECT SUMMARY
The claustrum is a narrow, subcortical sheet of gray matter with interconnections across the cerebral cortex. Its
irregular shape and deep location make it difficult to study with classical neurophysiological techniques. Recent
genetic technologies such as optogenetics provide new hope for understanding the claustrum. They have
advanced its study in rodents, implicating the claustrum in an array of sensorimotor and cognitive functions.
Circuit-specific studies are needed to resolve how these functions map to the claustrum’s widespread
connections. Such studies would be especially valuable in macaque monkeys, the animal model most
homologous to humans. My overall goal is to translate viral technologies to monkeys and use them to study the
role of a specific claustrum-prefrontal cortical circuit in visuo-saccadic behavior. During systematic testing of viral
vectors in macaques, I identified a promising candidate for delivering opsin genes to the claustrum: the
retrograde virus rAAV2-retro. When injected into the frontal eye field (FEF), a prefrontal cortical area involved in
vision, movement, and cognition, rAAV2-retro constructs yielded strong labeling of FEF-projecting claustrum
neurons. This finding provides a long-sought, unique opportunity to study claustrum neurons with circuit-level
specificity in the primate brain. I propose to validate viral techniques in the claustro-FEF circuit and use them to
test my overall hypothesis that the claustrum mediates competitive selection of the most behaviorally relevant
stimulus via suppression of all other stimuli. To test my hypothesis, I have three integrated aims. In Aim 1, I will
conduct anatomical tracing studies to elucidate the motif of connectivity between the claustrum and FEF. In Aim
2, I will use rAAV2-retro to express an inhibitory opsin in FEF-projecting claustrum neurons. Then I will use
phototagging to identify those neurons and extracellularly record from them to characterize the signals sent from
the claustrum to the FEF during a battery of saccade tasks. In Aim 3, I will use the same inhibitory opsins to
selectively silence FEF-projecting claustrum neurons, allowing me to determine whether they are required for
competitive selection of saccade targets. The claustrum is implicated in a wide range of neurological diseases
and neuropsychiatric disorders. Thus, the results of the proposed work will help reveal how pathological changes
to neural activity in the claustrum may contribute to brain disorders. In addition to its clinical relevance, the
proposed work will significantly expand my doctoral training to include neural recording and optogenetic methods
in non-human primates.

## Key facts

- **NIH application ID:** 10914128
- **Project number:** 5F31MH129122-03
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Hala Galal El-Nahal
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $41,436
- **Award type:** 5
- **Project period:** 2022-09-15 → 2025-09-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10914128

## Citation

> US National Institutes of Health, RePORTER application 10914128, Circuit-Specific Interrogation of the Primate Claustrum (5F31MH129122-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10914128. Licensed CC0.

---

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