HETEROSYNAPTIC PLASTICITY IN CA1 PYRAMIDAL NEURONS

01/29/2020

Adam Mago¹, Jens P. Weber¹, Balázs B. Ujfalussy¹, Judit K. Makara¹

¹ Institute of Experimental Medicine

Cortical principal neurons receive thousands of excitatory synaptic inputs onto their dendritic tree that are active in highly variable functional patterns. The spatiotemporal pattern of the input, together with the active and passive properties of the targeted dendrites, determines the integration mode of EPSPs along the dendritic segments. Furthermore, different input patterns may activate specific secondary molecular pathways that may lead to local functional changes such as long-term synaptic plasticity. Although long term potentiation (LTP) is a well-established plasticity mechanism of glutamatergic synapses in hippocampal CA1 pyramidal cells, the fine-scale input pattern requirements to induce potentiation so far remained unclear. Using 2-photon glutamate uncaging combined with whole-cell current clamp recordings, we have recently shown (Weber et al., 2016 Nature Comm.) that subthreshold cooperativity of spatially clustered, synchronously active inputs can lead to their homosynaptic LTP at distal segments of thin dendrites. Here we investigated whether local input patterns can also affect nearby synapses on the dendrite via heterosynaptic plasticity. We found that input patterns that are strong enough to trigger local dendritic regenerative events are able to induce potentiation in nearby synapses that are not part of the input pattern. This crosstalk between active input patterns and non-synchronous inputs is NMDA receptor dependent, is mediated by a local intracellular mechanism involving MEK/ERK signalling, does not require post-LTP activity, and is less reliable than homosynaptic plasticity. Our results suggest that multiple forms of local plasticity mechanisms can lead to functional clustering of synaptic inputs in dendrites.