Summary: Researchers have developed a comprehensive “toolbox” to establish that the mobility of receptors exists in intact brain tissue, and this mobility is critical for certain types of memory.
Neurons communicate with each other across synapses, areas of close contact where neurotransmitter molecules released from one neuron act on receptors embedded in the membrane of the opposite neuron.
Previous research conducted by the team of Daniel Choquet, a researcher at the CNRS and Director of the Interdisciplinary Institute for Neurosciences (CNRS/University of Bordeaux) had discovered that these receptors are not stationary, but instead move constantly in the membrane.
The same scientists suggested and indirectly demonstrated that this movement modifies the number of receptors in a synapse at a given time to modulate the effectiveness of synaptic transmission and, as a result, certain types of learning and memory.
Until now, however, it was not possible to observe receptor mobility in situ, in situations more natural than neuron cultures.
This has now been achieved: thanks to the development of a comprehensive ‘toolbox’, scientists have been able to establish that this mobility exists in intact brain tissue, and that it is indispensable for certain types of memory, such as the contextual fear memory tested in this study.
This ‘toolbox’ consists of a new animal model, improved high-resolution imaging technology and techniques for labeling and controlling receptor dynamics.
It will allow the study of any region of the brain in addition to the hippocampus, can be transposed to other types of receptors, and will be used by the team to study the possible role of receptor mobility in intellectual disabilities and autism spectrum disorders.
Funding: This research was supported by an ERC Advanced grant awarded to Daniel Choquet.
About this electrophysiology and memory research news
Auhtor: Veronique Etienne Source: CNRS Contact: Veronique Etienne – CNRS Image: The image is credited to Benjamin Compans and Daniel Choquet / IINS / CNRS-Université de Bordeaux
High-resolution imaging and manipulation of endogenous AMPA receptor surface mobility during synaptic plasticity and learning
Regulation of synaptic neurotransmitter receptor content is a fundamental mechanism for tuning synaptic efficacy during experience-dependent plasticity and behavioral adaptation. However, experimental approaches to track and modify receptor movements in integrated experimental systems are limited.
Exploiting AMPA-type glutamate receptors (AMPARs) as a model, we generated a knock-in mouse expressing the biotin acceptor peptide (AP) tag on the GluA2 extracellular N-terminal.
Cell-specific introduction of biotin ligase allows the use of monovalent or tetravalent avidin variants to respectively monitor or manipulate the surface mobility of endogenous AMPAR containing biotinylated AP–GluA2 in neuronal subsets. AMPAR immobilization precluded the expression of long-term potentiation and formation of contextual fear memory, allowing target-specific control of the expression of synaptic plasticity and animal behavior.
The AP tag knock-in model offers unprecedented access to resolve and control the spatiotemporal dynamics of endogenous receptors, and opens new avenues to study the molecular mechanisms of synaptic plasticity and learning.