Chemogenetic stimulation of tonic locus coeruleus activity strengthens the default mode network
E. Oyarzabal, Li-Ming Hsu, Manasmita Das, T. Chao, Jingheng Zhou, Shengdeng Song, Weiting Zhang, Kathleen G. Smith, Natale R. Sciolino, Irina Y Evsyukova, Hong Yuan, Sung-Ho Lee, Guohong Cui, Patricia Jensen, Y. Shih
Science Advances April 1, 2022 DOI: 10.1126/sciadv.abm9898 (opens in new tab) via Semantic Scholar
Summary
AI-generated from the abstractActivating norepinephrine-releasing neurons in the locus coeruleus (LC) of the mouse brain alters the default mode network (DMN). Chemogenetic stimulation of these neurons decreased cerebral blood volume and glucose uptake while increasing synchronous low-frequency fMRI activity in the frontal cortices of the DMN. Fiber photometry confirmed that LC-NE activation triggered norepinephrine release, enhanced calcium-weighted neuronal spiking, and reduced cerebral blood volume in the anterior cingulate cortex. These findings indicate that LC-NE changes the typical relationship between neuronal activity and blood volume in the frontal DMN. The activation also strengthened functional connectivity within the frontal DMN, an effect mediated by reduced inputs from retrosplenial and hippocampal regions.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Mice |
| Intervention | chemogenetic activation of LC-NE neurons |
| Keywords | Medicine Biology |
| Key finding | Chemogenetic activation of LC-NE neurons alters the coupling between neuronal activity and cerebral blood volume in the frontal default mode network and strengthens functional connectivity within that network. |
Abstract
The default mode network (DMN) of the brain is functionally associated with a wide range of behaviors. In this study, we used functional magnetic resonance imaging (fMRI), positron emission tomography (PET), and spectral fiber photometry to investigate the selective neuromodulatory effect of norepinephrine (NE)–releasing noradrenergic neurons in the locus coeruleus (LC) on the mouse DMN. Chemogenetic-induced tonic LC activity decreased cerebral blood volume (CBV) and glucose uptake and increased synchronous low-frequency fMRI activity within the frontal cortices of the DMN. Fiber photometry results corroborated these findings, showing that LC-NE activation induced NE release, enhanced calcium-weighted neuronal spiking, and reduced CBV in the anterior cingulate cortex. These data suggest that LC-NE alters conventional coupling between neuronal activity and CBV in the frontal DMN. We also demonstrated that chemogenetic activation of LC-NE neurons strengthened functional connectivity within the frontal DMN, and this effect was causally mediated by reduced modulatory inputs from retrosplenial and hippocampal regions to the association cortices of the DMN.