The Role of the Lateral Habenula in Controlling Itch Sensation and Behavior / Suna Li Cranfill.

Format:

Book

Thesis/Dissertation

Author/Creator:

Cranfill, Suna Li, author.

Contributor:

University of Pennsylvania. Neuroscience, degree granting institution.

Language:

English

Subjects (All):

Neurosciences.

Biomedical engineering.

Pathology.

Behavioral psychology.

Neuroscience--Penn dissertations.

Penn dissertations--Neuroscience.

Local Subjects:

Neurosciences.

Biomedical engineering.

Pathology.

Behavioral psychology.

Neuroscience--Penn dissertations.

Penn dissertations--Neuroscience.

Physical Description:

1 online resource (134 pages)

Distribution:

Ann Arbor : ProQuest Dissertations & Theses, 2023

Contained In:

Dissertations Abstracts International 85-08B.

Place of Publication:

[Philadelphia, Pennsylvania] : University of Pennsylvania, 2022.

Language Note:

English

Summary:

Itch is an aversive sensory experience that is inextricably linked to a drive to scratch. During acute itch, scratching serves a protective function and suppresses the inciting itch. During chronic itch, however, scratching becomes uncontrolled and pathological, leading to skin damage that exacerbates the underlying itch. Currently, effective treatments for chronic itch disorders are lacking due to the intractable nature of the itch-scratch cycle. While recent progress has advanced our understanding of itch sensation, the neural mechanisms underlying how scratching is sensed and controlled remain elusive. Here, we show that the lateral habenula (LHb), a brain region important for integrating aversive sensory information and suppressing motivated behavioral responses, plays a critical role in itch-induced scratching. The LHb is bilaterally activated by chloroquine (CQ)-evoked itch and scratching at the mouse cheek. However, the contributions of itch sensation and scratching behavior to LHb activation are asymmetric, with the contralateral LHb preferentially engaged by scratching. Using fiber photometry, we find that LHb calcium dynamics are correlated with scratching, activity increases are associated with the termination of scratching, and the ipsilateral and contralateral LHb exhibit distinct response patterns to pruritogen-evoked scratching. Moreover, gain-of-function manipulations reveal that contralateral, but not ipsilateral, CQ-activated LHb neurons are sufficient to suppress itch-evoked scratching in an itch intensity-dependent manner. Conversely, ipsilateral, but not contralateral, LHb neurons are required to promote itch-evoked scratching in an itch-intensity dependent manner. Using genetic approaches to investigate two genetically defined high-threshold mechanoreceptor (HTMR) populations, we find that nonpeptidergic type I (NP1) C-fiber HTMRs are required for scratching-evoked activation of the LHb, and itch behavior is disinhibited in NP1-ablated mice. We further show that a chronic itch mouse model for allergic contact dermatitis also activates the LHb, and the contralateral LHb plays a similar asymmetric role in suppressing spontaneous scratching as it does for pruritogen-evoked scratching. Collectively, this work reveals a periphery-to-brain pathway that controls itch-evoked scratching and provides a new perspective on how the itch-scratch cycle is dysregulated in chronic itch.

Notes:

Source: Dissertations Abstracts International, Volume: 85-08, Section: B.

Advisors: Luo, Wenqin; Ma, Minghong; Committee members: de Biasi, Mariella; Fuccillo, Marc V.; Song, Hongjun.

Department: Neuroscience.

Ph.D. University of Pennsylvania 2023.

Local Notes:

School code: 0175

ISBN:

9798381509786

Access Restriction:

Restricted for use by site license.