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ORIGINAL RESEARCH article

Front. Neurosci.
Sec. Translational Neuroscience
Volume 19 - 2025 | doi: 10.3389/fnins.2025.1544830

Chemogenetic modulation of the rat locus coeruleus alters hippocampal noradrenaline release and modulates perforant path-evoked responses

Provisionally accepted
Sielke Caestecker Sielke Caestecker 1*Emma Lescrauwaet Emma Lescrauwaet 1Kristl Vonck Kristl Vonck 1Mathieu Sprengers Mathieu Sprengers 1Evelien Carrette Evelien Carrette 1Paul AJM Boon Paul AJM Boon 1,2Lars Emil Larsen Lars Emil Larsen 1,3Robrecht Raedt Robrecht Raedt 1
  • 1 Department of Head and Skin, Faculty of Medicine and Health Sciences, Ghent University, Ghent, East Flanders, Belgium
  • 2 Department of Electrical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands
  • 3 Department of Electronics and Information Systems, Faculty of Engineering and Architecture, Ghent University, Ghent, East Flanders, Belgium

The final, formatted version of the article will be published soon.

    The locus coeruleus (LC)noradrenaline (NA) system plays a crucial role in modulating neuronal excitability and plasticity. In epilepsy, the LC-NA system plays an important role in regulating seizure thresholds and severity, with elevated NA release mediating the seizure-suppressing effects of vagus nerve stimulation (VNS). We investigated whether chemogenetic LC activation is able to increase hippocampal NA release and affect hippocampal electrophysiology in anesthetized rats. 22 male Sprague-Dawley rats were injected with the viral vector AAV9-hSyn-NE2m in the hippocampus to induce expression of the GRABNE2m biosensor to locally measure changes in extracellular NA. 15/22 rats were injected with the CAV2-PRSx8-hM3Dq hSyn-mCherry viral vector in the LC to express the excitatory DREADD hM3Dq, allowing LC activation with deschloroclozapine (DCZ), and 7/22 with CAV2-PRSx8-GtACR2 as a control. A perforant path stimulation electrode and a dentate gyrus (DG) recording electrode were implanted for local field potential (LFP) and evoked potential (EP) recording as well as a DG optical fiber for GRABNE2m fluorescence measurement. In a significant number of rats (7/15) we found an increase in hippocampal NA release, field excitatory post synaptic potential (fEPSP) slope and population spike (PS) amplitude, indicating an increase in excitatory neurotransmission and neuronal output. 4/15 rats showed a decrease in NA release without changes in fEPSP slope or PS amplitude, and 4/15 showed no change in NA release. These findings indicate that chemogenetic activation of the LC-NA system can modulate hippocampal evoked responses, supporting further exploration of its role in health and disease, such as in epilepsy.

    Keywords: Locus coeruleus (LC), Noradrenaline (NA), chemogenetics, GRABNE2m biosensor, Hippocampus (HC), evoked potentials (EPs), Epilepsy

    Received: 13 Dec 2024; Accepted: 03 Feb 2025.

    Copyright: © 2025 Caestecker, Lescrauwaet, Vonck, Sprengers, Carrette, Boon, Larsen and Raedt. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Sielke Caestecker, Department of Head and Skin, Faculty of Medicine and Health Sciences, Ghent University, Ghent, 9000, East Flanders, Belgium

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