PT  - JOURNAL ARTICLE
AU  - Francesco Gobbo
AU  - Laura Marchetti
AU  - Claudia Alia
AU  - Stefano Luin
AU  - Antonino Cattaneo
TI  - Activity-dependent expression of reporter proteins at dendritic spines for synaptic activity mapping and optogenetic stimulation
AID  - 10.1101/095984
DP  - 2016 Jan 01
TA  - bioRxiv
PG  - 095984
4099  - http://biorxiv.org/content/early/2016/12/21/095984.short
4100  - http://biorxiv.org/content/early/2016/12/21/095984.full
AB  - 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. Synaptic connections and pathways constitute the physical substrate that conveys information in the brain, and different combinations of active synaptic connections are believed to be responsible for the encoding of specific memories. In addition, modifications of the activity of such subsets of synapses are believed to be crucial for memory establishment, but a way to directly test this hypothesis, by selectively controlling the activity of potentiated spines, is currently lagging behind. Therefore it would be important to develop methods to tag active synapses for mapping functionally active connections and to selectively stimulate or interfere with active synapses. Here we introduce an approach to express light-sensitive membrane channels at synapses in an activity-dependent way by means of RNA and protein regulatory sequences. This approach is based on the local expression of reporter proteins, including optogenetic probes, at activated synapses and will allow the mapping of previously active synapses and the re-activation of the neuron only at these sites. This will allow extending the investigation of memory processes beyond the current neuron tagging technologies, whose resolution is limited at the cellular scale. Thus, it will be possible to unveil and recall the synaptic engram out of the global set of synapses.