Mapping of activated synapses in the hippocampus after context exploration with a new optogenetic reporter for spine potentiation.

Francesco Gobbo, Laura Marchetti, Bruno Pinto, Ajesh Jacob, Claudia Alia, Stefano Luin, Laura Cancedda, Antonino Cattaneo

Research output: Contribution to conferencePoster

Abstract

Increasing evidence points to the importance of dendritic spines in the formation and allocation of memories, and alterations of spine number and physiology are associated to memory and cognitive disorders. Modifications of the activity of subsets of synapses are believed to be crucial for memory establishment. In addition, theoretical models suggest the involvement of synapse clustering in memory related neuronal activity. However, many aspects regarding the spatial arrangement and the activity of potentiated synapses in vivo are still poorly understood. By combining Arc RNA regulatory sequences and a protein tag interacting with components of the postsynaptic density, we engineered an expression cassette (pSynActive) to drive the translation of a lightsensitive membrane channel at activated synapses in a regulated, inputspecific way. This hybrid approach provides a new methodology to (i) map and (ii) tag potentiated synapses with optogenetic probes, as well as other reporter proteins. By means of in utero electroporation, we delivered this potentiation reporter in mouse hippocampus. We were thus able to tag synapses in vivo in a defined time window, making use of a tetracyclineinducible promoter. We mapped activated synapses in the hippocampal regions CA1 and dentate gyrus, and compared the resulting synaptic ensembles in mice that were maintained in the home cage to mice that explored a novel environment. We found significant differences in terms of number and spatial arrangement of activated synapses following the novel context exposure, and highlight peculiarities in their distribution between CA1 and the dentate gyrus. Hence, this approach looks promising for the mapping of potentiated synapses in the brain, and could make it possible to reactivate the neuron only at previously activated synapses,
extending current neuron tagging technologies in the investigation of memory processes at the synaptic level.
Original languageEnglish
Publication statusPublished - 2017
Externally publishedYes
EventNeuroscience 2017 - Washington, DC
Duration: 11 Nov 201715 Jan 2019

Conference

ConferenceNeuroscience 2017
CityWashington, DC
Period11/11/1715/01/19

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