RT Journal Article
SR Electronic
T1 Activity-dependent expression of reporter proteins at dendritic spines for synaptic activity mapping and optogenetic stimulation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 095984
DO 10.1101/095984
A1 Francesco Gobbo
A1 Laura Marchetti
A1 Claudia Alia
A1 Stefano Luin
A1 Antonino Cattaneo
YR 2016
UL http://biorxiv.org/content/early/2016/12/21/095984.abstract
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.