Hippocampal Seizures Strongly Modulate the Activity of Locus Coeruleus Neurons
Abstract number :
1.025
Submission category :
1. Basic Mechanisms / 1C. Electrophysiology/High frequency oscillations
Year :
2022
Submission ID :
2204106
Source :
www.aesnet.org
Presentation date :
12/3/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:23 AM
Authors :
Lars Larsen, PhD – Ghent University; Sielke Caestecker, MSc – PhD candidate, 4Brain, Ghent University; Paul Boon, MD, PhD – Professor, 4Brain, Ghent University; Kristl Vonck, MD, PhD – Professor, Ghent University; Robrecht Raedt, PhD – Professor, 4Brain, Ghent University
This abstract is a recipient of the Young Investigator Award
This abstract has been invited to present during the Basic Mechanisms platform sessionThis abstract has been invited to present during the Basic Science Poster Highlights poster session
Rationale: The locus coeruleus (LC), a deep brainstem nucleus, is the sole source of norepinephrine (NE) in the neocortex, hippocampus and cerebellum. Previous studies suggest activation of the LC and increased levels of noradrenaline in relation to seizures. In this study, we conduct a detailed assessment of the response of locus coeruleus neurons and changes in LC-NE transmission during acute hippocampal seizures in rats.
Methods: Male Sprague-Dawley rats were anesthetized and stereotactically implanted with recording electrodes in the hippocampus and a stimulation electrode in the perforant path for electrogenic seizure induction. The activity of LC neurons was measured in relation to evoked seizures using 32-channel silicon probes. LC neurons were identified based on electrophysiological characteristics or with optogenetics. In a separate experiment, changes in hippocampal NE-transmission during seizures were assessed using a fluorescent biosensor for NE, GRABNE2m, in combination with fiber photometry. All animal experiments complied with local and European guidelines and regulations and were approved by the local committee for animal experiments (ECD 19/42).
Results: In 9 rats, a total of 97 LC neurons were identified. Hippocampal seizures were associated with strong changes in neuronal firing rates (Figure 1). A total of 54/97 (56%) neurons were significantly inhibited by seizures, 27/97 (28%) neurons were significantly excited by seizures, while 16/97 (16%) neurons showed no significant change. Topographic visualization of multi-unit activity during seizures revealed a tendency for excited and inhibited neuronal activity to be organized in anatomically distinct clusters in multiple animals. Despite a majority of LC neurons showing decreased firing during evoked hippocampal seizures, hippocampal seizures were nevertheless associated with a strong increase in hippocampal NE-transmission assessed with the GRABNE2m sensor (Figure 2).
Conclusions: Hippocampal seizures, evoked by perforant path stimulation, leads to a mixture of activation and inhibition of locus coeruleus neurons, which appeared organized in anatomically distinct clusters. The fact that hippocampal seizures nevertheless resulted in increased hippocampal NE-transmission suggests that the minority of excited LC neurons during seizures project to the hippocampus. Future research will determine the role of the observed seizure-related LC response in modulating seizure activity, which is likely to be important to understanding seizure pathophysiology.
Funding: This project is supported by grants from the Research Foundations Flanders (FWO; 11M6422N and 1216520N) and the Queen Elisabeth Medical Foundation (GSKE) for Neurosciences.
Basic Mechanisms