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Séminaire - Sylvain Williams Optogenetic control of interneurons in hippocampus reveals their role in rhythm generation and bi-directional communication.

Abstract :

My laboratory is interested in understanding how the hippocampus is able to encode and recall memory. We have focused our attention on a type of brain activity named theta rhythm which predominates when the animal is exploring the environment and during REM sleep and is know to be essential for memory. However, very little is known about how theta rhythm is generated.

For over a decade, modeling studies had predicted that specific types of interneurons with the markers somatostatin were key in their generation. In the first part of the talk, I will show that the optogenetic control of specific types of interneurons can generate population activity in an in vitro isolated hippocampus that is optimal at theta frequencies.

Lastly, canonical models suggest that information flow in hippocampus is serially routed across regions from the dentage gyrus through CA3, CA1 and subiculum. By using optogenetic manipulation of neurons,  I will present new evidencethat this model may be incorrect and that infromation flow may be bidirectional in hippocampus. Our results provide new insights into information processing in the hippocampus.

Selected publications

Goutagny R, Jackson J, Williams S. Self-generated theta oscillations in the hippocampus. Nat Neurosci. 2009 Dec;12(12):1491-3.
For a summary see: Hippocampal theta rhythms follow the beat of their own drum. By Colgin LL, Moser EI. Nat Neurosci. 2009 Dec;12(12):1483-4.

Gu N, Jackson J, Goutagny R, Lowe G, Manseau F, Williams S. NMDA-dependent phase synchronization between septal and temporal CA3 hippocampal networks. J Neurosci. 2013 May 8;33(19):8276-87.

Huh CY, Goutagny R, 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 Neurosci. 2010 Nov 24;30(47):15951-61.

Jackson J, Goutagny R, Williams S. Fast and slow gamma rhythms are intrinsically and independently generated in the subiculum. J Neurosci. 2011 Aug 24;31(34):12104-17. PubMed PMID: 21865453.

Goutagny R, Gu N, Cavanagh C, Jackson J, Chabot JG, Quirion R, Krantic S, Williams S. Alterations in hippocampal network oscillations and theta-gamma coupling arise before Aβ overproduction in a mouse model of Alzheimer's disease. EJNeurosci. 2013 Jun;37(12):1896-902

Scientific focus :

Profile  more..Douglas Mental Health University Institute
Understanding the neural circuits underlying learning and memory is the major research focus of Sylvain Williams, PhD, a member of the Douglas Institute Research Centre since 1999.

Memories are central to our personal identity and essential to our everyday 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 work together seemlessly to encode and recall information.

Sylvain William is interested in how large population of neurons interact synaptically to produce brain rhythmic activities that are critical for learning and memory. In addition, understanding the mechanisms of how neurons of the hippocampus behave as a population will give powerful insights into what’s wrong with the neural circuitry in Alzheimer’s disease and schizophrenia.

Sylvain Williams and his team are pursuing several complementary lines of study aimed towards discovering the neural circuits underlying learning and memory. For example, they have developed a unique approach using a complete hippocampus formation preparation in vitro in combination with electrophysiology, immunohistochemistry and molecular biology, to reveal which neurons can generate brain oscillations.

Moreover, they have also developed optogenetics, which offers the unique capability to manipulate specific groups of neurons with light to better understand their role in neural circuits and brain rhythms. They also developed a special interest in determining the role of identified neurons in freely behaving animal during learning and memory.

Together, these research approaches promise to shed light on how memory processes can become disrupted ultimately giving rise to the development of Alzheimer Disease.