# Elucidating cellular activity patterns underlying spinal cord function

> **NIH NIH R01** · SALK INSTITUTE FOR BIOLOGICAL STUDIES · 2021 · $420,875

## Abstract

PROJECT SUMMARY
A key unresolved question in neuroscience is how different cell types and their activity patterns contribute to
sensory processing in the central nervous system. Anatomical and physiological measurements indicate that
computations underlying somatosensation are initiated in the dorsal horn of the spinal cord. Genetic,
electrophysiological, and circuit-tracing methods have identified a number of neuronal populations involved in
this process, as well as their potential contributions. Likewise, histologic, pharmacologic, and genetic studies
have revealed important roles for glial cells in the pathogenesis and resolution of aberrant sensations.
However, despite these advances, little is known about the dynamic neuronal and glial activity patterns, or the
interactions between them, that underlie the moment-to-moment processing of innocuous and noxious stimuli.
The recent development of novel two-photon and miniaturized one-photon imaging approaches has enabled
stable measurement of cellular calcium excitation in the spinal dorsal horn of behaving animals. These
technologies have provided the first insights into how sensory information from mechanoreceptors and
nociceptors in the skin activates dorsal horn neurons and astrocytes. Using cutting-edge imaging, optogenetic,
and pharmacological approaches, the objective of this proposal is to define how the activity patterns of different
types of dorsal horn neurons shape astrocyte calcium excitation, and how astrocyte excitation influences
neuronal spiking under physiological and pathophysiological conditions. The rationale for the proposed
research is that by uncovering the bi-directional relationship between neuron and astrocyte activity in the spinal
dorsal horn, new strategies for pain relief may be developed. Three specific aims will be pursued: 1) Determine
how sensory evoked activity patterns in molecularly defined neurons relate to astrocyte calcium excitation in
the spinal dorsal horn of behaving animals; 2) Determine how aberrant neuronal activity patterns in preclinical
models of pain relate to astrocyte calcium excitation in the spinal dorsal horn of behaving animals; and 3)
Determine how targeted manipulation of astrocyte calcium excitation controls aberrant neuronal activity
patterns in the spinal dorsal horn of behaving animals. In summary, this work will reveal how molecularly
defined neurons encode different sensory stimuli and how their activity patterns relate to astrocyte calcium
excitation. These efforts will also reveal how normal activity patterns are altered in two animal models of pain
and how pharmacologic and non-pharmacologic interventions targeting astrocytes affect aberrant neuronal
activity and sensory processing.

## Key facts

- **NIH application ID:** 10130007
- **Project number:** 5R01NS108034-03
- **Recipient organization:** SALK INSTITUTE FOR BIOLOGICAL STUDIES
- **Principal Investigator:** Axel Nimmerjahn
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $420,875
- **Award type:** 5
- **Project period:** 2019-04-15 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10130007

## Citation

> US National Institutes of Health, RePORTER application 10130007, Elucidating cellular activity patterns underlying spinal cord function (5R01NS108034-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10130007. Licensed CC0.

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