Optogenetic Control of Synaptic Composition and Function

• Published in: Neuron (Cambridge, Mass.) Vol. 93; no. 3; pp. 646 - 660.e5
• Main Authors: Sinnen, Brooke L., Bowen, Aaron B., Forte, Jeffrey S., Hiester, Brian G., Crosby, Kevin C., Gibson, Emily S., Dell’Acqua, Mark L., Kennedy, Matthew J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 08.02.2017; Elsevier Limited
• Subjects: AMPA receptor; Animals; Arabidopsis Proteins - genetics; Basic Helix-Loop-Helix Transcription Factors - genetics; Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism; CaMKII; Colleges & universities; CRY2; cryptochrome; Cryptochromes - genetics; GluA1; Hippocampus - cytology; Kinases; Light; Localization; Long-Term Potentiation; LTP; Microscopy; Neuronal Plasticity - genetics; Neurons - metabolism; optogenetics; Optogenetics - methods; Patch-Clamp Techniques; plasticity; Post-Synaptic Density - metabolism; Proteins; PSD; Rats; Rats, Sprague-Dawley; Receptors, AMPA - genetics; Recruitment; Rodents; Software; synapse; Synapses - metabolism; Synapses - physiology; Synaptic Membranes - metabolism; PSD; AMPA receptor; CaMKII; optogenetics; cryptochrome; CRY2; plasticity; LTP; synapse; GluA1
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2016.12.037

The molecular composition of the postsynaptic membrane is sculpted by synaptic activity. During synaptic plasticity at excitatory synapses, numerous structural, signaling, and receptor molecules concentrate at the postsynaptic density (PSD) to regulate synaptic strength. We developed an approach that uses light to tune the abundance of specific molecules in the PSD. We used this approach to investigate the relationship between the number of AMPA-type glutamate receptors in the PSD and synaptic strength. Surprisingly, adding more AMPA receptors to excitatory contacts had little effect on synaptic strength. Instead, we observed increased excitatory input through the apparent addition of new functional sites. Our data support a model where adding AMPA receptors is sufficient to activate synapses that had few receptors to begin with, but that additional remodeling events are required to strengthen established synapses. More broadly, this approach introduces the precise spatiotemporal control of optogenetics to the molecular control of synaptic function. •A new method for rapidly and locally tuning the level of synaptic proteins in the PSD•Adding AMPA receptors to the PSD elevated quantal frequency; amplitude was unaffected•Data support the presence of silent synapses that contain few or no AMPA receptors•Functional subdomains within the PSD limit quantal amplitude Sinnen et al. developed an approach to rapidly control the molecular composition of the postsynaptic density with light. Adding neurotransmitter receptors to the PSD had surprising functional effects that support a requirement for precise receptor positioning within PSD subdomains.