Mechanisms of neural synchrony and entrainment (epilepsy) and neurodegenerative processes

We have several projects on cellular mechanisms of epilepsy, particularly the synchronizing role of electrotonic coupling via gap junctions and the role of presynaptic neurotransmitter release. Molecular biological and cellular electrophysiological recording techniques are being used in several seizure models, including hippocampus and neocortical tissue. This also includes the study of pannexins in epilepsy in collaboration with Dr. Georg Zoidl of York University. In collaboration with Drs. Georg Zoidl and James Reynolds (Queen’s University), we are examining the pathophysiological bases of the brain dysfunction found in the fetal alcohol spectrum disorder, particularly the role of gap junctions. We are also studying the efficacy of a novel set of molecules to repair the blood brain barrier (BBB), discovered by Dr. Philippe Monnier (Krembil), in models of aging/Alzheimer disease and for the fetal alcohol syndrome, all of which show impairments of the BBB measured in vivo. With Dr. Bojana Stefanovich (Sunnybrook Hospital), we are studying the relationship between acute strokes and seizures in vivo.

In collaboration with Dr. Berj Bardakjian (IBBME), the linear and nonlinear electrical and network properties of central mammalian neurons in physiological and pathophysiological conditions (eg, epilepsy) are being described by neural modelling techniques. We are developing nonlinear techniques for the identification of different brain states including those associated with anesthesia and epilepsy. Future work will involve the use of artificial intelligence and “deep machine learning” for interpretation of brain wave signals to identify different brain states and seizure activity.

The origin of Sudden Unexpected Death in Epilepsy (SUDEP) remains unknown but we hypothesize that it is a result of seizure activity in the brainstem. We are now recording in vivo cerebral and brainstem EEG in freely moving animals with epilepsy. To further the study of epilepsy in vivo, we are collaborating with Drs. Mike Thompson (Chemistry, U of T) and Roman Genov (Electrical Engineering, U of T) to implement novel recording systems including the use of electrodes treated with antifouling chemistry for long-term intracranial measurements of various chemical species including potassium, glucose, oxygen and neurotransmitters. Also, in collaboration with Dr. Ofer Levi, we are implementing optical and acoustic recordings for the measurement of cerebral blood flow and oxygenation in vivo.
Neurobiol Dis. 2019 Oct 24;:104628
Lertwittayanon W, Devinsky O, Carlen PL
IEEE J Transl Eng Health Med. 2019;7:2000203
Jacobs D, Liu YH, Hilton T, Del Campo M, Carlen PL, Bardakjian BL
Neurobiol Dis. 2019 Jun 07;130:104488
Kalitzin S, Petkov G, Suffczynski P, Grigorovsky V, Bardakjian BL, Lopes da Silva F, Carlen PL
J Vis Exp. 2019 Jan 19;(143):
Chang M, Dufour S, Carlen PL, Valiante TA
J Neurosci. 2019 Jan 29;:
Gondard E, Teves L, Wang L, McKinnon C, Hamani C, Kalia SK, Carlen PL, Tymianski M, Lozano AM
Ann Clin Transl Neurol. 2019 Jan;6(1):167-173
Wennberg R, Maurice C, Carlen PL, Garcia Dominguez L
Biomed Opt Express. 2018 Nov 01;9(11):5615-5634
Ringuette D, Nauenberg J, Monnier PP, Carlen PL, Levi O
Stroke. 2018 Sep;49(9):2173-2181
Bazzigaluppi P, Lake EM, Beckett TL, Koletar MM, Weisspapir I, Heinen S, Mester J, Lai A, Janik R, Dorr A, McLaurin J, Stanisz GJ, Carlen PL, Stefanovic B
Front Mol Neurosci. 2018;11:338
Bazzigaluppi P, Adams C, Koletar MM, Dorr A, Pikula A, Carlen PL, Stefanovic B
Front Cell Neurosci. 2018;12:278
Song H, Mylvaganam SM, Wang J, Mylvaganam SMK, Wu C, Carlen PL, Eubanks JH, Feng J, Zhang L


Professor, Department of Medicine, Department of Physiology, Institute of Biomaterials and Biomedical Engineering, and Institute of Medical Science, University of Toronto