Evoked hippocampal seizures are associated with bursts of locus coeruleus neuronal activity in the anaesthetized rat: a mechanism of ‘pathological memory formation’ in epilepsy?
Lars
E.
Larsen1, 2*,
Latoya
Stevens2,
Anirudh
Acharya2,
Charlotte
Bouckaert2,
Erine
Craey2,
Jana
Desloovere2,
Marie-Gabrielle
Goossens2,
Charlotte
Germonpré2,
Silke
Proesmans2,
Paul
Boon2,
Kristl
Vonck2,
Chris
Vanhove1,
Pieter
Van Mierlo1 and
Robrecht
Raedt2
-
1
Medical Imaging and Signal Processing, Ghent University, Belgium
-
2
Department of Head and Skin, Faculty of Medicine and Health Sciences, Ghent University, Belgium
Epilepsy is one of the most common neurological disorders with an estimated worldwide prevalence of 0.5-1% (WHO). Despite an explosion in development of novel antiepileptic drugs over the past decades, a third of patients remain medication resistant. Lack of therapeutic success is likely multifactorial but can be partially attributed to a general lack in understanding of pathological mechanisms in epilepsy (Kwan, Arzimanoglou et al. 2010). In this preliminary study in one rat, we challenged a classical dogma that epilepsy is a predominant cortical disorder, by examining the role of the noradrenergic brainstem nucleus, the locus coeruleus, in relation to seizures. Under isoflurane anaesthesia, seizures were evoked at 10 minute intervals with tetanic electrical bursts (10 seconds, 20 Hz, 1 ms pulse width, 400 mA). Throughout the experiment, hippocampal field activity (CA1 and dentate gyrus) and locus coeruleus (LC) unit activity was registered continuously. Hippocampal seizures, evoked by performant path stimulation, were associated with bursts of LC unit activity (Figure 1). Though intraperitoneal administration of clonidine, an α2-adrenoceptor agonist, suppressed LC activity, bursts of LC activity still occurred in relation to seizures. The LC-noradrenergic system is known to play an important role in regulation of excitability in large scale networks, synaptic plasticity and memory (Lim, Tan et al. 2010; Quinlan, Strong et al. 2018). We therefore hypothesize that the observed phenomenon may be a mechanism supporting the formation and consolidation of seizure networks in relation to seizures – in essence a pathological memory. This increases the likelihood of future recruitment of the network and thus future seizure occurrence, a process known as kindling. Future experiments are needed to determine the role of the LC in kindling and epileptogenesis.
References
Kwan, P., A. Arzimanoglou, et al. (2010). "Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies." Epilepsia 51(6): 1069-1077.
Lim, E. P., C. H. Tan, et al. (2010). "Locus coeruleus stimulation and noradrenergic modulation of hippocampo-prefrontal cortex long-term potentiation." Int J Neuropsychopharmacol 13(9): 1219-1231.
Quinlan, M. A. L., V. M. Strong, et al. (2018). "Locus Coeruleus Optogenetic Light Activation Induces Long-Term Potentiation of Perforant Path Population Spike Amplitude in Rat Dentate Gyrus." Front Syst Neurosci 12: 67.
WHO. from http://www.who.int/news-room/fact-sheets/detail/epilepsy.
Keywords:
Epilepsy,
seizure,
Locus coeruleus (LC),
Pathological memory,
Hippocampal seizures
Conference:
13th National Congress of the Belgian Society for Neuroscience , Brussels, Belgium, 24 May - 24 May, 2019.
Presentation Type:
Poster presentation
Topic:
Behavioral/Systems Neuroscience
Citation:
Larsen
LE,
Stevens
L,
Acharya
A,
Bouckaert
C,
Craey
E,
Desloovere
J,
Goossens
M,
Germonpré
C,
Proesmans
S,
Boon
P,
Vonck
K,
Vanhove
C,
Van Mierlo
P and
Raedt
R
(2019). Evoked hippocampal seizures are associated with bursts of locus coeruleus neuronal activity in the anaesthetized rat: a mechanism of ‘pathological memory formation’ in epilepsy?.
Front. Neurosci.
Conference Abstract:
13th National Congress of the Belgian Society for Neuroscience .
doi: 10.3389/conf.fnins.2019.96.00016
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Received:
29 Apr 2019;
Published Online:
27 Sep 2019.
*
Correspondence:
Dr. Lars E Larsen, Medical Imaging and Signal Processing, Ghent University, Ghent, East Flanders, Belgium, larsemil88@gmail.com