@article{01JMEK6H1NVA4XHV9PWJZBFZSY,
  abstract     = {{Introduction: 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. Methods: 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. Results: 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. Discussion: These findings indicate that chemogenetic activation of the LCNA system can modulate hippocampal evoked responses, supporting further exploration of its role in health and disease, such as in epilepsy.}},
  articleno    = {{1544830}},
  author       = {{Caestecker, Sielke and Lescrauwaet, Emma and Vonck, Kristl and Sprengers, Mathieu and Carrette, Evelien and Boon, Paul and Larsen, Lars Emil and Raedt, Robrecht}},
  editor       = {{Burger, Corinna}},
  issn         = {{1662-453X}},
  journal      = {{FRONTIERS IN NEUROSCIENCE}},
  keywords     = {{locus coeruleus,noradrenaline,chemogenetics,GRABne2m biosensor,hippocampus,evoked potentials,epilepsy,VAGUS NERVE-STIMULATION,DENTATE GYRUS,POPULATION SPIKE,NOREPINEPHRINE RELEASE,NORADRENERGIC SYSTEM,EPSP SLOPE,INHIBITION,ORGANIZATION,FACILITATION,TERMINALS}},
  language     = {{eng}},
  pages        = {{14}},
  title        = {{Chemogenetic modulation of the rat locus coeruleus alters hippocampal noradrenaline release and modulates perforant path-evoked responses}},
  url          = {{http://doi.org/10.3389/fnins.2025.1544830}},
  volume       = {{19}},
  year         = {{2025}},
}

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