# Determine Functions of the Lateral Habenular and Trigeminal High Threshold Mechanoreceptors in Mediating Scratching-induced Responses

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2024 · $510,721

## Abstract

PROJECT SUMMARY
Itch is defined as an unpleasant sensation that triggers the desire to scratch. During acute itch, scratching
only
eventually
becomes
depression.
itch/scratching
not
 helps to get rid of pruritogens but also triggers strong mechanical sensation or mechanical pain) that
suppresses the itch sensation and stops f urther scratching. During chronic itch, however, scratching
 uncontrollable, which leads to excessive scratching, skin lesions, anxiety, sleep deprivation, and
At present, how scratching information is sensed in the skin and processed in the brain to suppress
 is largely unknown. 
(
We find that lateral habenula (LHb) neurons are bilaterally activated after
acute pruritogen administration to one side of the mouse cheek, indicating that LHb neurons may respond to
chemical itch sensation and/or scratching-induced mechanosensation. Interestingly, LHb neuronal activation is
significantly reduced in the contralateral side when mice wear collars to prevent scratching, which suggests that
some scratching information is preferentially transmitted to the contralateral LHb. Moreover, re-activation of
either bilateral or contralateral itch/scratching-evoked LHb neurons suppresses scratching. Thus, we raise a
novel hypothesis that the LHb integrates both scratching-induced mechanosensory and chemical itch sensory
inputs and suppress scratching in a lateralized manner and that cutaneous high-threshold mechanoreceptors
are required to transmit scratching information to the LHb. We will use a combination of cutting-edge techniques
to test this hypothesis. In Aim 1, we will thoroughly examine molecular, circuit, and physiological properties of
itch/scratching-activated LHb neurons on the contralateral vs ipsilateral side, with or without collar. We will also
record population calcium signal changes of LHb neurons in vivo in response to scratching. In Aim 2, we will test
the functional sufficiency and requirement of LHb neurons in suppressing scratching evoked by acute and
chronic itch using chemogenetic and optogenetic manipulations as well as LHb neuronal ablation. Finally, in
Aim 3, we will ablate C and/or Aδ high threshold mechanoreceptors (HTMRs), which mediate strong mechanical
or mechanical pain sensation, to test their functional requirements in transmitting scratching information to the
LHb and suppressing scratching. Taken together, our anticipated results will reveal novel neural circuits in
mediating the sensation of scratching and controlling scratch, an exciting area that is largely unexplored but
highly relevant for alleviating chronic itch.

## Key facts

- **NIH application ID:** 10873021
- **Project number:** 5R01NS131209-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Wenqin Luo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $510,721
- **Award type:** 5
- **Project period:** 2023-06-20 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10873021

## Citation

> US National Institutes of Health, RePORTER application 10873021, Determine Functions of the Lateral Habenular and Trigeminal High Threshold Mechanoreceptors in Mediating Scratching-induced Responses (5R01NS131209-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10873021. Licensed CC0.

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