# Circuit structure and dynamics in prefrontal-limbic networks

> **NIH NIH R01** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2024 · $591,433

## Abstract

ABSTRACT
The ability to regulate when and how emotions are used to guide cognition relies on adaptive and plastic circuits
that can integrate internal limbic-visceral and external sensory-motor information for a given behavioral context.
The anterior cingulate cortex (ACC) is an area that plays an important role in this process of emotional regulation
and multimodal integration, acting as a unique connectional node for the otherwise segregated cognitive, motor
and limbic networks. The ACC forms a robust network with the amygdala (AMY), a key limbic structure for
emotion and arousal, which exhibits specialized circuit reorganization and plasticity during emotional stress. Our
previously funded R01 (MH116008) focused on comparing the ACC with the lateral prefrontal cortex (LPFC),
another region implicated in cognition and stress, and on the extrinsic ACC pathways to cognitive/motor and
limbic areas. It remains unclear how exactly these multimodal pathways interact across the functionally distinct
rostral ‘cognitive’ (a32), ventral ‘limbic’ (a25) and dorsal ‘motor’ (a24) subdivisions of the ACC, which is the focus
of this renewal application. Our work in the previous grant period has shown that the robust ACC interconnections
with AMY span all ACC areas and are therefore, well-suited for integrating information across these distinct ACC
functional domains. Further, compared to ACC projections to cognitive/motor areas in LPFC and dorsal premotor
(PMd) cortices, AMY-targeting ACC pyramidal neurons show greater laminar diversity in their distribution, and
biophysical, structural, and inhibitory synaptic properties. Computational modeling show that these unique single-
cell biophysical and connectional properties contribute to diverse laminar oscillatory dynamics in ACC outputs to
AMY, which can support synchrony at low frequencies in L5, but at high frequencies in L3. In contrast, cortico-
cortical ACC outputs to PMd are more tuned towards higher oscillatory frequencies in both layers. While we have
shown how these extrinsic ACC outputs are diverse at the single cell level, the question remains as to how
multimodal information is integrated within the ACC. This renewal focuses on the largely uncharacterized short-
range interconnections within and between the functionally distinct ACC areas that are likely important for this
multimodal integration. Using anatomical tract-tracing, optogenetics, slice physiology, high-resolution
microscopy and computational modeling we propose to assess intrinsic ACC-ACC interconnections in adult
rhesus monkeys (5-13Y) with regards to their: excitatory vs inhibitory constituents, neuromodulation of synaptic
plasticity, interactions with long-range cognitive (LPFC), motor (PMd) and limbic (AMY) pathways, and
contributions to diverse network dynamics. The overall hypothesis is that distinct short-range intrinsic ACC
circuits have specialized excitatory, inhibitory and neuromodulatory properties and interactions with
long-r...

## Key facts

- **NIH application ID:** 10801057
- **Project number:** 2R01MH116008-06
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Maria Medalla
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $591,433
- **Award type:** 2
- **Project period:** 2019-04-01 → 2028-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10801057

## Citation

> US National Institutes of Health, RePORTER application 10801057, Circuit structure and dynamics in prefrontal-limbic networks (2R01MH116008-06). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10801057. Licensed CC0.

---

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