Joana Ferreira, Laurent Groc et al in PNAS

Tell me where you are, I will tell you how you are

A key feature of glutamatergic synapses, which mediate most of excitatory synaptic transmission in the central nervous system, more than 80 Two years ago, is their capacity to adapt their strength to salient stimuli. This central capacity is partly driven by the ionotropic glutamatergic NMDA receptor (NMDAR) that can trigger long-term synaptic changes. Our lab unveiled that NMDAR are not distributed randomly within synapses. NMDAR form nanoscale-packed clusters that were termed nanodomains in hippocampal synapses. Yet, neurons exhibit myriads of synapses along their long dendritic trees that are known to have different properties. It is thus possible that nothing is more different to a glutamate synapse than another one located at another dendrite location! In this collaborative work (Groc’s and Sibarita’ labs), we here unveil that NMDAR are differently organized into nanodomains depending on their localization along the dendritic tree. Furthermore, this greatly influences the synaptic response to changes in activity. When NMDAR are located close to the cell body, in proximal dendritic segments and mainly contain GluN2B-NMDAR, they are dynamically regulated by activity through their interaction with the intracellular partner CaMKII. However, towards the tip of the dendritic tree of neuron, in the so-called distal dendritic segments, NMDAR are more packed and less stirring, exhibiting different functional properties that influence synaptic plasticity. This study sheds thus a new light on the differences in NMDAR-dependent adaptation mechanisms previously observed and unexplained along the dendritic tree.

Article

Distance-dependent regulation of NMDAR nanoscale organization along hippocampal neuron dendrites
Joana S Ferreira, Julien P Dupuis, Blanka Kellermayer, Nathan Bénac, Constance Manso, Delphine Bouchet, Florian Levet, Corey Butler, Jean-Baptiste Sibarita, and Laurent Groc
PNAS, 14 Sept 2020
https://doi.org/10.1073/pnas.1922477117