Transcriptomic and spatial GABAergic neuron subtypes in zona incerta mediate distinct innate behaviors

Area of Science:

• Neuroscience
• Molecular Biology
• Behavioral Science

Background:

• Understanding transcriptomic neuron subtypes is crucial for mapping brain functions.
• The zona incerta (ZI) is implicated in modulating various behaviors, but its neuronal subtypes remain poorly understood.

Purpose of the Study:

• To dissect the molecular identity and function of heterogeneous GABAergic neuron populations within the mouse zona incerta (ZI).
• To reveal the specific neuronal circuits and behaviors mediated by distinct GABAergic neuron subtypes in the ZI.

Main Methods:

• Single-nucleus transcriptomic sequencing
• In vivo circuit mapping
• Optogenetic and chemogenetic approaches
• Spatial gene expression analysis of the ZI

Main Results:

• Identified two non-overlapping GABAergic neuron populations in the ZI, Ecel1-expressing (ZIrEcel1) in the rostral ZI and Pde11a-expressing (ZImPde11a) in the medial ZI.
• Demonstrated that ZIrEcel1 projections to the periaqueductal gray mediate self-grooming behavior.
• Showed that ZImPde11a projections to the pontine reticular formation promote the transition from sleep to wakefulness.

Conclusions:

• Revealed molecular markers, spatial organization, and specific neuronal circuits for two discrete GABAergic projection neuron populations in the ZI.
• These findings advance the understanding of functional organization within the ZI and its role in innate behaviors.
• The study provides a foundation for further investigation into ZI-mediated behaviors and neurological disorders.