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A double dissociation of presynaptic NMDA receptor signalling in neocortex

Start: Jun 29, 2017 01:00 PM
End: Jun 29, 2017 02:00 PM

Location: Ground floor Lecture Theatre, Sainsbury Wellcome Centre, 25 Howland Street, London W1T 4JG

Part of the SWC Seminar Series
Speaker: Dr Jesper Sjöström, Associate Professor, Department of Neurology and Neurosurgery, Research Institute of the McGill University Health Centre

NMDARs are critically involved in Hebbian plasticity, but they need to be located postsynaptically to serve this function. Yet, many studies have found enigmatic presynaptic NMDARs (preNMDARs) that regulate both evoked and spontaneous release. However, controversy and disagreement is widespread in the preNMDAR research field. For example, one inconsistency is the fact that preNMDARs require high-frequency activation to regulate evoked release, yet they also regulate spontaneous release at very low frequencies. We use a battery of cutting-edge techniques such as 2-photon imaging, photo-uncaging, quadruple patch, conditional genetic deletion, and computer modelling to demonstrate that preNMDARs rely on the classic presynaptic active-zone protein RIM1 to upregulate the replenishment rate of the readily releasable pool during high-frequency spiking: RIM1 deletion abolishes this regulation as well as preNMDAR-mediated bouton supralinearities. Spontaneous release, however, surprisingly remains unaffected. Conversely, preNMDAR regulation of spontaneous but not evoked release requires JNK2. This double dissociation in preNMDAR signalling helps resolve the above frequency inconsistency, which has been a long-standing conundrum in the field. These findings also support the emerging principle that evoked and spontaneous release rely on distinct mechanisms.

Jesper Sjöström

Biography:

Dr Jesper Sjöström is an Associate Professor in the Department of Neurology and Neurosurgery at the Research Institute of the McGill University Health Centre. His research is focused on the mechanisms, phenomenology, and functional consequences of Spike-Timing-Dependent Plasticity (STDP) in neocortical circuits. His team employs two-photon laser scanning microscopy, quadruple whole-cell recordings, optogenetics, and computational modelling. 

Dr Sjöström obtained his PhD in 2002 at Brandeis University, working under the supervision of Dr Sacha B. Nelson. Between 2003 and 2007, he did his postdoctoral studies in the lab of Michael Häusser at University College London. Until 2011, Dr Sjöström ran an independent lab at University College London as a Medical Research Council Career Development Fellow.

Time: 1-2pm, Thursday 29 June 2017

Location: Ground floor Lecture Theatre, Sainsbury Wellcome Centre, 25 Howland Street, London W1T 4JG

Host: Troy Margrie

No need to pre-book, just turn up!