6875 Boulevard Lasalle
Dept of Psychiatry
Douglas hospital research center
The Williams hippocampal rhythm laboratory
The goal of the laboratory is to understand how brain rhythms are generated and their role in memory and in Alzheimer's disease
Memories are central to our personal identity and essential to our every day life. However, how memories are created or recalled remains incompletely understood. What we know though is that the hippocampus, the learning and memory center of the brain, contains millions of neurons that have to synchronize together seemlessly for memory to function. When neurons synchronize brain rhythms can be recorded extracellularly. In the hippocampus, theta frequency rhythm (4-12 Hz) and higher frequency gamma rhythms (40-190 Hz) are the most prominent oscillations and they are necessary for long-term depression and potentiation which are cellular substrates for learning and memory. My laboratory is interested in understanding how different types of neurons, especially GABAergic interneurons , synchronize and participate in generating hippocampal rhythms and memory formation. We also want to determine the role of oscillations in learning and memory.
The laboratory uses an array of unique tools including the recent development of a complete mature hippocampal preparation maintained alive in vitro. The isolated hippocampus preparation offers several key advantages over brain slices because it preserves all neuronal connectivity. Because of normal cellular interactions, the isolated hippocampus has the capacity to self-generate theta rhythm in addition to faster frequency gamma oscillations without the aid of pharmacology. This preparation offers an exceptional opportunity to investigate the cellular mechanisms underlying brain rhythm generation with single-cell patch and field recordings in combination with pharmacology. In addition, we also use a recently developed technique named optogenetics which is a powerful method using light activation to finely control the activity of specific neuronal populations within a network. Lastly, we also perform electrophysiology and optogenetics in freely behaving animals to determine the role of specific neural circuits in learning and memory.
Benedicte Amilhon, Carey Y.L. Huh, Frederic Manseau, Guillaume Ducharme, Heather Nichol, Antoine Adamantidis, and Sylvain Williams. Parvalbumin Interneurons of Hippocampus Tune Population Activity at Theta Frequency. Neuron 86, 1–13, June 3, 2015.
Jesse Jackson, Bénédicte Amilhon, Romain Goutagny, Jean-Bastien Bott, Frédéric Manseau, Christian Kortleven*, Steven L. Bressler, & Sylvain Williams. Reversal of theta rhythm flow through intact hippocampal circuits", Nature Neuroscience, 2014,
GU N, JACKSON J. , GOUTAGNY R., LOWE G. , Manseau F. and Williams S. NMDA dependent phase synchronization between septal and temporal CA3 hippocampal networks. J. Neuroscience, 2013, 33(19), 8276-87.
Goutagny R., Gu N. , Cavanagh C., Jackson J, Chabot J-G, Quirion R, Krantic S and Williams S. Alterations in hippocampal network oscillations and theta-gamma coupling arise before A overproduction in a mouse model of Alzheimer’s disease. European J. Neuroscience, 2013, 37(12), 1896-902.
Ducharme, G., Goutagny, R. , Lowe, G. and Williams S.. Early alterations in hippocampal circuitry and theta rhythm generation in a mouse model of prenatal infection: Implications for schizophrenia. PLOS ONE 2012;7(1):e29754.
Jackson, J, Goutagny, R, and Williams, S. Fast and slow gamma rhythms are intrinsically and independently generated in the subiculum. J.Neuroscience, 2011. Aug 24;31(34):12104-17.
Williams S. and Boksa. Gamma oscillations and Schizophrenia. Journal of Psychiatry and Neuroscience. Editorial, J Psychiatry Neurosci. 2010 Mar;35(2):75-7.
Huh CY.L., Goutagny R, and Williams S. Glutamatergic neurons of the mouse medial septum and diagonal band of Broca synaptically drive hippocampal pyramidal cells: relevance for hippocampal theta rhythm. J.Neuroscience 2010, November 24, 2010, 30(47):15951-15961.
GoutagnyR, Jackson JJ., Williams S. Self-generated theta oscillations in the hippocampus. Nature Neuroscience. 2009 Dec;12(12):1491-3. Reviewed in the Nature Neuroscience NEWS AND VIEWS: Hippocampal theta rhythms follow the beat of their own drum. By Colgin LL, Moser EI. Nat Neurosci. 2009 Dec;12(12):1483-4. F1000 reviewed.
Following a PhD at Université de Montréal in the neurological sciences with Dr Jean-Claude Lacaille (1989-94), I was a postdoctoral fellow with Drs Michel Muhlethaler and Laurent Bernheim at Geneva University in Switzerland (1994-97). There I explored the role of physiological properties of septal and basal forebrain cells in producing network activity. I also did a one year postdoc at the University of Calgary with Brian MacVicar to study cytokines, imaging and neuromodulation. In February 1999, I moved to the Douglas Hospital to set-up my own laboratory. I was named assistant professor of psychiatry at McGill in 1999, associate professor in 2007, and full professor in 2015.
Frédéric Manseau, Research Associate
Jean-Bastien Bott, postdoctoral fellow
Amilhon Bénédicte, postdoctoral fellow
Guillaume Etter, postdoctoral fellow
Jun-Li Kang, postdoctoral fellow
Amy Chee, postdoctoral fellow
Eva Eco Varela, Doctorate
Jennifer Robinson, Doctorate
Boyce Richard, Doctorate,
Guillaume Ducharme, Doctorate
Heather Nichol, Master's
Causal evidence for the role of REM sleep theta rhythm in contextual memory consolidation. Science. 2016;352(6287):812-6.
Optogenetic Activation of Septal Glutamatergic Neurons Drive Hippocampal Theta Rhythms. J Neurosci. 2016;36(10):3016-23.
Activation of specific neuronal networks leads to different seizure onset types. Ann Neurol. 2016;79(3):354-65.
Interneuron activity leads to initiation of low-voltage fast-onset seizures. Ann Neurol. 2015;77(3):541-6.
Reversal of theta rhythm flow through intact hippocampal circuits. Nat Neurosci. 2014;17(10):1362-70.
Phosphorylation of tau protein at sites Ser(396-404) is one of the earliest events in Alzheimer's disease and Down syndrome. Neuropathol Appl Neurobiol. 2014;40(2):121-35.
Regulation of the Hippocampal Network by VGLUT3-Positive CCK- GABAergic Basket Cells. Front Cell Neurosci. 2017;11:140.
REM sleep and memory. Curr Opin Neurobiol. 2017;44:167-177.
Optogenetic Low-Frequency Stimulation of Specific Neuronal Populations Abates Ictogenesis. J Neurosci. 2017;37(11):2999-3008.
Specific imbalance of excitatory/inhibitory signaling establishes seizure onset pattern in temporal lobe epilepsy. J Neurophysiol. 2016;115(6):3229-37.
Resilience to chronic stress is mediated by noradrenergic regulation of dopamine neurons. Nat Neurosci. 2016;19(4):560-3.
Parvalbumin Interneurons of Hippocampus Tune Population Activity at Theta Frequency. Neuron. 2015;86(5):1277-89.