Reserach projects

Current members of the lab:

Attila Sík, Ph.D.
Lucy Foss, PhD Student
Andor Magony, PhD Student
Kaustuv Basu, Postdoctoral fellow
Alex Ferecsko, Postdoctoral fellow
Krisztina Kovacs, Postdoctoral fellow

Lab members in the past:

Orsolya Szalay, Technician
Philippe Lemieux, Technician
Sebastien Herbert , Summer student
Guy Charette, Summer student
Helene Guay, Summer student
Laetitia Davidovic, Ph.D. Student
Jocelin Guay, Research Assistant
Amelie Cote, Research Assistant
Frederic Dumont, Master Student
Gabrielle Girardeau, Master Student (internship)
Jonathan Vinet, Postdoctoral fellow
Helene Guay, Research Assistant
Albert David Tamburri, MPhil Student

Ongoing major research projects

Hippocampus is a brain structure playing a crucial role in learning and memory processes. This brain area is also the focus of many neurodegenerative diseases like epilepsy, traumatic brain injuries, ischemia and different psychiatric disorders. To have a better understanding of the function of the hippocampus in normal and pathological conditions the functional neuroanatomical basis of the hippocampus has to be revealed. It requires a deep knowledge of the connectivity of the neurons, localization of different receptors and ion channels at cellular and subcellular level.

The hippocampal formation consists of two major neuron types: glutamatergic excitatory principal cells and GABAergic inhibitory neurons. While much of our understanding of the function of the hippocampus derives from studies on principal cells, little is know about the properties of inhibitory interneurons. Yet, interneurons play a crucial role in the processing of information in this area of the brain. One of the most remarkable features of the hippocampal principal cells is their ability to change the strength of the synaptic connections in an activity dependent manner, termed long-term potentiation (LTP) and long-term depression (LTD). Calcium has been shown to play a crucial role in these processes, but Ca2+-dependent synaptic plasticity is not uniform in all cell types. Moreover, interneurons also greatly differ from principal cells with regards to Ca2+-induced cell death: specific subpopulations of interneurons are extremely vulnerable and degenerate very rapidly following an excitotoxic insult, while others appear to be particularly resistant. The objective of this research is to determine how distinct expression patterns and subcellular distributions of calcium channels characterize the different subpopulations of hippocampal interneurons.

Epileptic seizures result from large number of excitatory neurons firing in pathological synchrony such that normal brain function is partially or completely disrupted. Experimental data suggest that electrotonic communication between neurons via intercellular connections is an important synchronizing mechanism that contributes to the generation and maintenance of seizure.

Electrotonic synaptic communication between neurons via gap junctions (GJ) is hypothesized to be a key element in electrotonical synchronization. Research results show that connexin, protein that builds up GJ, is expressed in hippocampal pyramidal neurons and granule cells, which might explain the synchronous activity of neurons during epileptic seizure. However, immunohistochemical studies have failed to confirm the presence of connexin proteins in these neurons.

The nature of the electrotonical communication between principal cells has not yet been revealed. The question arises 1) Is electrotonical communication in the hippocampus enhanced during seizures in vivo? 2) What is the anatomical manifestation of the increased electrotonical coupling? 3) Can dye coupling be a real indication to the presence of GJ? 4) How neurons are " electrotonically connected" to each other in during epilepsy?

The seminal role for electrotonical coupling in the generation of seizure is becoming clear. Whether it is due to GJ or other mechanism is still remained to be determined. Development of future anticonvulsant drug requires basic knowledge of the nature of electrical coupling. My research project is designed to unveil the anatomical feature of electrotonical coupling taking place during seizures thus might find answer to some of the controversial issues that have arisen over the last several decades.

3) Electrical activity of hippocampal inhibitory neurons in epileptic brains in vivo

Temporal lobe epilepsy is characterized by synchronized discharges of large number of hippocampal excitatory cells. Diminished and/or altered inhibition is one of the causes of this abnormal activity. We investigated the modes of discharges of different types of CA1 hippocampal inhibitory neurons in anaesthetized animals in normal condition, during the transition to epileptiform state induced by bicuculline infusion and in epileptiform activity. We recorded the electrical activity of inhibitory neurons using juxtacellular single cell recording technique and firing patterns were correlated with extracellularly recorded network activity. The recorded neurons were identified morphologically and neurochemically. Different types of inhibitory neurons behaved distinctly during various phases of epileptiform activity. We distinguished 5 main modes of discharges of inhibitory neurons depending on their firing pattern during spike, wave and inter-burst phases of interictal events. In each phase of epileptiform activity different types of inhibitory neurons were active. The heterogeneous firing activity of inhibitory neurons indicates that inhibition is still present in epilepsy and not diminished but the inhibition of distinct compartment of pyramidal cells, innervated by different inhibitory neurons, is greatly altered.

4) Role of long-range projection inhibitory neurons in the hippocampal network synchronization

Proper function of the hippocampus, which is a crucial brain area for memory and learning processes, requires a well-orchestrated activity of neurons. The synchronization in the neural network is mainly maintained by inhibitory neurons, which make up only 10% of the cell population. As demonstrated before different inhibitory cells have various functions in the network activity. Locally acting neurons are the best studied in the inhibitory cell group because the commonly utilized brain slicing method relatively marginally alters the connectivity of this type of cells. However, inhibitory neurons with long axonal arborization eluded researcher until today because the investigation requires intact brain preparation. We believe that long projection inhibitory neurons have a critical role in the hippocampal function and organization. This cell type can synchronize neural activity in large populations of cells through its extensive axonal arborization. Moreover, this cell type can even synchronize the activity of the two hippocampi. We investigate the functional significance of this special type of neuron in network synchronization by using various neuroanatomical and electrophysiological methods combined with utilizing virus constructs and transgenic animals.

To address these questions the following methods are used in the lab routinely:

Immunohistochemistry (single and double staining), 2D and 3D reconstruction of neurons, light (Transmitted, Fluorescent, Epipolarization, Phase contrast) and electron microscopical (TEM) methods, quantitative light and electron microscopy techniques, Cryo electron microscopy, Track tracing methods, in vivo extracellular and juxtacellular recordings, multichannel recording in vivo. etc. In addition Cryo electron tomography will be used in the lab in the near future.

The newly renovated laboratory is equipped with a state-of-the-art Electron Microscope (Phillips Tecnai 12), coupled to a Soft Imaging MegaView II CCD camera system for digital image acquisition and analysis (AnalySIS software), ultramicrotome ( Leica Ultracut UCT), an automated cryo-fixation and cryo-substitution system for lowicryl embedding and post-embedding immunocytochemical protocols (Leica Automated Freeze Substitution System) and a fluorescent light microscope (Olympus AX 70) coupled to Spot CCD camera, Tucker-Davis 128 channel recording system, single-cell electroporation system, etc