# Neuronal anatomy, connectivity, and phenotypic innervation of the knee joint

> **NIH NIH UC2** · BAYLOR COLLEGE OF MEDICINE · 2022 · $7,388,710

## Abstract

PROJECT SUMMARY
Identifying patterns of neuronal connectivity is critical for understanding functional and anatomical circuits that
mediate pain perception. However, knowledge about the types and distribution of neurons in joint tissues have
generally been limited to traditional 2-dimension histopathological and immunohistopathological approaches,
and little to no information is available on connectivity and neuronal phenotypes. New technologies have
emerged that allow for both trans-synaptic circuit analysis and precise control of neuronal firing, including the
use of retrogradely transported viral vectors (i.e., pseudotyped rabies virus) and heterologous receptor
activation. At the same time, 3-dimensional visualization of neuronal and vascular patterns have been
advanced by tissue clearing techniques in conjunction with cell type specific fluorescent markers generated by
intercrossing cell type specific Cre recombinase mouse lines with a variety of conditionally activated reporters.
Finally, the advent of single cell RNA sequencing has allowed for extending cellular phenotyping to a molecular
level that has not only increases analytic resolution, but also therapeutic targeting with greater disease
specificity than previously possible. The development of high resolution spatial transcriptomics, i.e., MERFISH,
allows for correlation and validation of scRNA-seq data. In this context, osteoarthritis of the knee joint is an
optimal model for applying these tools as abundant genetic and surgical models are available for orthogonal
validation of findings. Moreover, in the preclinical context, various therapeutic approaches including gene
therapy have been shown to impact pain measures, and as such, they constitute an important interventional
validation of molecular changes that are identified in neurons in the disease state. The fact that some of these
therapies are now in clinical trial adds to the potential translational impact of the proposed preclinical findings
here. Ultimately, the combination of both anatomic, 3-D, and molecular signatures will facilitate the translation
into human tissues and biopsies, while maximizing the likelihood of relevant new therapeutic targets.

## Key facts

- **NIH application ID:** 10608851
- **Project number:** 1UC2AR082200-01
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Benjamin R Arenkiel
- **Activity code:** UC2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $7,388,710
- **Award type:** 1
- **Project period:** 2022-09-23 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10608851

## Citation

> US National Institutes of Health, RePORTER application 10608851, Neuronal anatomy, connectivity, and phenotypic innervation of the knee joint (1UC2AR082200-01). Retrieved via AI Analytics 2026-08-13 from https://api.ai-analytics.org/grant/nih/10608851. Licensed CC0.

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