Peter Carlen

Research Synopsis

Research Divisions: Brain Research and Integrated Neurophysiology

Research Interests: Membrane and synaptic properties of mammalian CNS neurons/glia; Physiological, pharmacological and pathological studies of seizure disorders, using electrophysiological recordings, imaging and molecular biological techniques in vitro and in vivo; cerebral extracellular potassium regulation; brainstem seizures; and the use of human cerebral organoids derived from embryonic stem cells and from humans with epilepsy to study epilepsy and mitochondrial related disorders.

Keywords: Cellular Electrophysiology/ Gap Junctions/synapses/ Epilepsy/Hypoglycemia/ Fetal alcohol syndrome.

Detailed Description:
Main interests are mechanisms of neural synchrony and entrainment (epilepsy), neurodegenerative conditions, and hypoglycemic seizures.

a) We have several projects on cellular mechanisms of epilepsy, particularly the biophysics of the transition to seizure, and the role of electrotonic coupling via gap junctions. Cellular and local network electrophysiological, molecular biological and optogenetic techniques are being used to measure the upregulation of gap junctions in several in vitro seizure models. In collaboration with Dr. Taufik Valiante, detailed neurodynamical electrophysiological studies of human brain tissue removed at resective operation for intractable epilepsy are underway.

b) In collaboration with Drs. Berj Bardakjian and Taufik Valiante, the linear and nonlinear electrical and network properties of central mammalian neurons in physiological and pathophysiological conditions (e.g. epilepsy) are being described by neural modelling techniques. We are also developing in vivo animal models for the study of seizure anticipation and prevention using an artificial neural network and a homology function. This approach of seizure detection and prevention has the potential of being applied to patients with intractable, drug-resistant epilepsy. We are also assessing brain states using signal processing techniques, with immediate application to the level of anesthesia in human subjects.

c) In collaboration with Dr. Roman Genov (Dept of Electrical Engineering) and Dr. Berj Bardakjian and Dr. Ofer Levi, we are implementing the development of brain implantable microchips for EEG and other biosensor (blood flow, oxygenation) data acquisition and adaptive feedback neural control. So far we have tested this system in vitro, with the ultimate aim of having a wireless implantable system. The longterm neurological clinical applications of such technology are enormous.

d) In animal models and a model of the fetal alcohol syndrome, gap junctional communication and brain excitability are under investigation.

e) We are studying the pathophysiology of hypoglycemic seizures in juvenile animals both in vitro and in vivo. Hypoglycemic seizures are a major problem in juveniles with diabetes.

METHODS USED

Cell and tissue culture: Brain slice, hippocampal cells, neurons.

Procedures: EEG, electrophysiology, immunohistochemistry, in-vitro electrophysiology, in-vivo electrophysiology, in-vivo recording of local field potentials, intracellular injection, micro and macrostimulation of peripheral nerves and central brain structures, patch clamp, qRT-PCR, siRNA, voltage clamp, western blot, optogenetics

EQUIPMENT USED

Amplifier, calcium imaging system, confocal microscope, digidata, dissecting microscope, electrophysiology rig, fluorescence microscope, infusion apparatus, micropipette puller, motorized micromanipulators, pressure osmometer, real-time/thermocycler, stimulator, vibratome, water baths.

PRESENT TRAINEES

Suzie Dufour, Postdoctoral student
Lihua Wang, Postdoctoral student
Paolo Bazzigaluppi, Postdoctoral student
Wanida Nuwisait, PhD student
Marija Cotic, PhD student, co-supervised with Dr. Berj Bardakjian, IBBME
Mirna Guirgis, PhD student, co-supervised with Dr. Berj Bardakjian, IBBME
Josh Dian, PhD student, co-supervised with Dr. Berj bardakjian
Ryan McGinn, MSc, IBBME
Sonia Sugumar, MSc student
Vanessa Breton, MSc student
Meera Ramani, Research Associate
Shanthi Mylvaganam, Research Associate
Michal Krawczyk, Research student

PRESENT COLLABORATIONS

Within the Department of Physiology:
Milton Charlton
Adria Giacca

Outside the Department of Physiology:
Berj Bardakjian, IBBME
Roman Genov, IBBME
Ofer Levi, IBBME
Jose Luis, Perez Velazquez IMS/HSC
Milos Popovic, IBBME
Taufik Valiante, IMS
Georg Zoidl, York
Christian Naus, UBC
Yosi Yarom, Hebrew University
James Reynolds, Queens
Mike Poulter, UWO

Committee member/Officer of national or international scientific organization:
Associate Editor, Journal of Neural Engineering
President, Eastern Association of EEG
Member, North American Committee of the ILAE

Appointments

Primary: Medicine