# A novel method for transient and repeatable axonal tracing in developing marmosets

> **NIH NIH R21** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2022 · $427,810

## Abstract

PROJECT SUMMARY
Preclinical animal models of neurodevelopmental disorders (NDDs), including autism spectrum disorders (ASDs)
and those of intellectual disabilities, have yielded insight into candidate genetic etiologies, but circuit-level
hypotheses underlying behavioral alterations (particularly social impairments) have remained elusive. A
significant challenge for developing biomarkers and diagnostic tools has been technological – because canonical
neuronal tract-tracing techniques require histology of post-mortem tissue, longitudinal assessments of circuit
development are few and far between. To address this critical unmet need, we propose to develop a novel,
transient, and repeatable method that circumvents invasive histochemistry altogether and allows for longitudinal
axonal-level tracing in developing marmoset monkeys. The common marmoset (Callithrix jacchus) is an ideal
preclinical modeling species for studying circuit trajectories related to aberrant social development. We recently
discovered that marmosets, like humans, possess socially selective face processing patches in frontal cortex.
As such, marmosets can recapitulate primate-specific aspects of social behaviors that form the diagnostic criteria
for many NDDs. In Aim 1, we will optimize our approach, which uses transcranial focused ultrasound (FUS) to
deliver MnCl2, a magnetic resonance imaging (MRI)-visible axonal tracer to any prescribed region of the brain.
In Aim 2, we seek to demonstrate that the FUS-MEMRI technique is a reliable screening tool for developmental
circuit-level aberrations with test-retest reliability. We will leverage our genetically diverse breeding colony of
marmosets to study the structural underpinnings of naturally occurring differences in social face processing from
an early age. From two months into adulthood, we will employ the FUS-MEMRI method to track the axonal
connectivity of our previously identified socially selective face patch in medial frontal cortex. This circuity is
ostensibly involved in assigning social salience to faces, a classic hallmark deficit in ASDs. By employing our
established fMRI paradigm – which is passive and can be used with very young marmosets – we will link axonal
development to functional variability in social processing of faces. Further, we will employ trained machine-
learning algorithms to isolate gaze patterns to relevant facial features, providing a behavioral index of face
processing. With this noninvasive multimodal approach, we will establish parameters of healthy variability of this
circuitry in our marmoset population, laying the groundwork for genetic and pharmacological models currently in
development by our laboratory and others. This work will lead to the establishment of a novel noninvasive
approach for longitudinal axonal tracing that is transient, targeted, and repeatable. This technique will have broad
application in translational research, especially for neurodevelopmental applications, providing a mean...

## Key facts

- **NIH application ID:** 10526658
- **Project number:** 1R21NS125372-01A1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** David J Schaeffer
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $427,810
- **Award type:** 1
- **Project period:** 2022-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10526658

## Citation

> US National Institutes of Health, RePORTER application 10526658, A novel method for transient and repeatable axonal tracing in developing marmosets (1R21NS125372-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10526658. Licensed CC0.

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