Inhibitory medial zona incerta pathway drives exploratory behavior by inhibiting glutamatergic cuneiform neurons
Sandeep Sharma,
Cecilia A. Badenhorst,
Donovan M. Ashby,
Stephanie A. Vito,
Michelle A. Tran,
Zahra Ghavasieh,
Gurleen K. Grewal,
Cole R. Belway,
Alexander McGirr and
Patrick J. Whelan ()
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Sandeep Sharma: University of Calgary
Cecilia A. Badenhorst: University of Calgary
Donovan M. Ashby: University of Calgary
Stephanie A. Vito: University of Calgary
Michelle A. Tran: University of Calgary
Zahra Ghavasieh: University of Calgary
Gurleen K. Grewal: University of Calgary
Cole R. Belway: University of Calgary
Alexander McGirr: University of Calgary
Patrick J. Whelan: University of Calgary
Nature Communications, 2024, vol. 15, issue 1, 1-17
Abstract:
Abstract The cuneiform nucleus (CnF) regulates locomotor activity, which is canonically viewed as being primarily involved in initiating locomotion and regulating speed. Recent research shows greater context dependency in the locomotor functions of this nucleus. Glutamatergic neurons, which contain vesicular glutamate transporter 2 (vGLUT2), regulate context-dependent locomotor speed in the CnF and play a role in defensive behavior. Here, we identify projections from the medial zona incerta (mZI) to CnF vGLUT2 neurons that promote exploratory behavior. Using fiber photometry recordings in male mice, we find that mZI gamma-aminobutyric acid (GABA) neurons increase activity during periods of exploration. Activation of mZI GABAergic neurons is associated with reduced spiking of CnF neurons. Additionally, activating both retrogradely labeled mZI-CnF GABAergic projection neurons and their terminals in the CnF increase exploratory behavior. Inhibiting CnF vGLUT2 neuronal activity also increases exploratory behavior. These findings provide evidence for the context-dependent dynamic regulation of CnF vGLUT2 neurons, with the mZI-CnF circuit shaping exploratory behavior.
Date: 2024
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45288-x
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DOI: 10.1038/s41467-024-45288-x
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