# Development of Synaptic Inputs on Spinal Interneurons

> **NIH NIH R01** · EMORY UNIVERSITY · 2021 · $459,312

## Abstract

PROJECT SUMMARY (30-lines)
Movement depends on patterned spinal cord motor output necessary for coordinated muscle actions. This
in turn, depends on spinal interneuron microcircuits that modulate motoneuron recruitment and firing. The
recent explosion of genetically-defined interneurons has revolutionized the study of spinal motor circuits
promising a more comprehensive and complete dissection of these important networks. The work started
by devising genetic strategies to identify, label, study and modify activity of large groups of interneurons
defined by their derivation from specific progenitor domains. This is the approach mostly taken in previous
years. Much new information was obtained, but the biggest surprise was the large heterogeneity within
each domain-lineage of spinal interneurons. It is thus now necessary to study the different subclasses of
interneurons within each domain. This can only be accomplished with new animal models to target more
restricted subgroups using intersectional genetics in which combinatorial expression of more than one
gene is necessary for conditionally expressing fluorescent proteins or activity modulators to study them.
This grant focuses on the V1 group. These are inhibitory interneurons with ipsilateral connections in the
spinal cord and that have important roles shaping motoneuron activity. Over the years we and others have
reported a variety of functions for V1 interneurons, including control of motoneuron firing by recurrent and
reciprocal inhibition, being all Renshaw cells and some, but not all, Ia inhibitory interneurons (IaINs)
derived from V1s. They also contribute to regulate flexion-extension alternation during movement and
locomotion speed, providing respectively out-of-phase and in-phase inhibition during rhythmic locomotion.
This functional diversity is parallel by the existence of many different genetically-defined subpopulations
(by some estimates more than 50) organized into four major V1 clades. It is now important to analyze
whether each subset is integrated in distinct microcircuits and responsible for specialized functions. We
chose to focus in the next five years on the largest V1clade defined by the transcription factor Foxp2. Data
gathered during the previous grant suggest this group is composed of at least three major subtypes and
includes some cells with synaptology typical of IaINs. We have tested various intersectional strategies to
study anatomically (using various viral approaches) the connectivity of Foxp2-V1s with different motor
pools and primary afferents, and the postnatal development of these connections (Aim1). Then, we will
analyze whether Foxp2-V1s are the only sources of V1-IaINs and how reciprocal inhibition is affected by
genetically silencing them (Aim 2). Finally, we will reversibly silence these cells in the neonate and adult
during locomotor stepping and use chronic EMG recordings and kinematics to analyze their role in muscle
activation selection during rhythmi...

## Key facts

- **NIH application ID:** 10211518
- **Project number:** 2R01NS047357-14
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** FRANCISCO J ALVAREZ
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $459,312
- **Award type:** 2
- **Project period:** 2004-06-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10211518

## Citation

> US National Institutes of Health, RePORTER application 10211518, Development of Synaptic Inputs on Spinal Interneurons (2R01NS047357-14). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10211518. Licensed CC0.

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