All-Optical Investigation of Schaller Collateral Synapses in vivo

Ensembles of neurons in the hippocampus encode the position of an animal navigating in the environment. Although exposed to the same environment over days, the neuronal representation is drifting and new ensembles emerge. Nonetheless the animal’s behavioral performance appears stable over time despite the neuronal drift. While the cellular dynamics of hippocampal coding are well-described, how information is encoded and preserved at the level of individual synapses during spatial navigation is less understood. The drift of the spatial representation in the hippocampus could be a consequence of its high spine turnover, as reported in some studies. Yet, other studies reported high spine stability in the hippocampus. While the relationship to functional synaptic changes remains elusive in vivo, studies in vitro identified a tight link between synaptic plasticity and stability. Here, we aim to understand how synaptic activity and plasticity influence the spine lifetime in vivo, by relating synaptic functional recordings to structural changes in spines at cornu ammonis (CA1) pyramidal cells. We chronically imaged dendritic spines on CA1 cells in the awake mouse, monitoring their synaptic responses to optogenetically stimulated presynaptic CA3 cells. Using this approach, we were able to induce local, synaptic calcium responses at individual spines and to assess the stability of these functionally identified synapses over two weeks. We show that optogenetically identified spines were more stable over days than non-responding, neighboring spines. This suggests that functional connectivity predicts synapse stability. As a consequence, synaptic weights may determine long-term synaptic connectivity and therefore neuronal network connectivity. Finally, this data further highlights the diversity of spine properties and provides basis on integrating further these properties, which determines systems connectivity, for future bio-inspired model of brain function.