Brain-Wide Connectivity of GLP1R Neurons in the Thalamic Reticular Nucleus

Area of Science:

• Neuroscience
• Metabolic Signaling
• G-protein-coupled receptors

Background:

• Glucagon-like peptide-1 receptor (GLP1R) is crucial for metabolic homeostasis and insulin secretion.
• Central GLP1R signaling influences sensory processing and cognitive functions.
• The thalamic reticular nucleus (TRN) filters sensory information, but its GLP1R neuron connectivity is unknown.

Purpose of the Study:

• To map the whole-brain inputs and outputs of GLP1R-expressing neurons within the TRN.
• To characterize the long-range structural connectivity of these specific neurons.

Main Methods:

• Utilized Glp1r-Cre mice with viral-genetic tracing.
• Employed a Cre-dependent retrograde rabies virus system for monosynaptic input identification.
• Used a Cre-dependent synaptophysin-based tracing strategy for efferent projection mapping.

Main Results:

• Identified GLP1R neurons predominantly in the mid-TRN.
• Mapped extensive inputs from motor cortices, somatosensory cortex, and thalamic nuclei (VL, CL, Po).
• Revealed projections from TRN^GLP1R neurons to specific thalamic nuclei (VM, PC, MDL) and the lateral habenula (LHb).

Conclusions:

• Confirmed complex long-range afferent and efferent circuits involving TRN^GLP1R neurons.
• Established a morphological foundation for understanding their role in integrating metabolic states with sensory gating.