# Organization and Circuit Interactions of Thalamocortical Attentional Networks in Health and Disease

> **NIH NIH R01** · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · 2021 · $460,899

## Abstract

PROJECT SUMMARY
The inhibitory thalamic reticular nucleus (TRN) envelops the dorsal thalamus. The TRN is poised to gate thalamo-
cortical signals through two-way connections with the dorsal thalamus, and as the recipient of unidirectional
pathways from the entire cerebral cortex. We previously discovered that three interconnected regions in
primates, the mediodorsal thalamic nucleus (MD), specific prefrontal cortices (PFC) and the amygdala innervate
the frontal, as well as the sensory TRN sectors. This evidence suggests prefrontal control of attention to help
select salient stimuli for flexible, goal directed behavior. These developments highlight the need to systematically
evaluate the as-yet unknown microcircuitry linking TRN with dorsal thalamic nuclei, which give rise to laminar-
specific pathways to cortex. These studies are predicated on primate specializations that may underlie normal
and pathologic function through thalamus and cortex in humans. Our working hypothesis is that
neurochemically-distinct inhibitory TRN neurons have specific synaptic interactions within TRN. In
addition, distinct inhibitory TRN neurons have specialized connections with ‘core’ thalamic neurons that
focally drive activity in the middle cortical layers, and ‘matrix’ thalamic neurons that broadly innervate
the upper cortical layers. Experiments are designed to test this hypothesis by systematic study of: (1) the
molecular and synaptic organization of neurochemically-distinct TRN neurons within TRN sectors; (2) pathways
to TRN from: a model sensory thalamic nucleus, the visual lateral geniculate, which is connected with the visual
cortex; and a model high-order thalamic nucleus, the MD, which is connected with PFC and the amygdala; (3)
TRN pathways directed to each of these dorsal thalamic nuclei; (4) and use of the rich database obtained on
excitatory and inhibitory circuits to simulate normal function within the TRN and dorsal thalamus, and disruption
in disease. Identical high-resolution methods will be used to study pathway interactions in rhesus monkeys and
humans. Excitatory and inhibitory pathways will be labeled using molecular, cellular and synaptic features that
differentiate bidirectional circuits of TRN with dorsal thalamic nuclei to reliably separate them from other
pathways. Quantitative analyses will be based on data from correlated confocal and electron microscopy, and
3D-reconstruction of pathways and synapses at multiple scales of resolution. Hypotheses about pathway
interactions are based on a theoretical framework on the organization of corticothalamic networks and the
significant expansion and specialization of TRN in parallel with the dorsal thalamus and cortex in primates.
Findings from these studies will provide the circuit basis for the role of TRN and the thalamocortical systems in
attentional modulation for sensory, cognitive and emotional processes and their disruption in sleep disorders and
attention deficits in schizophrenia and autism...

## Key facts

- **NIH application ID:** 10071885
- **Project number:** 5R01MH118500-03
- **Recipient organization:** BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
- **Principal Investigator:** Arash Yazdanbakhsh
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $460,899
- **Award type:** 5
- **Project period:** 2019-02-15 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10071885

## Citation

> US National Institutes of Health, RePORTER application 10071885, Organization and Circuit Interactions of Thalamocortical Attentional Networks in Health and Disease (5R01MH118500-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10071885. Licensed CC0.

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