Periodic Reporting for period 2 - DeCode (Dendrites and memory: role of dendritic spikes in information coding by hippocampal CA3 pyramidal neurons)
Reporting period: 2019-12-01 to 2021-05-31
The recurrent synaptic network of pyramidal cells (PCs) in the hippocampal CA3 area, receiving external inputs from the entorhinal cortex and the dentate gyrus, is thought to be essential for associative memory. Current models of the associative functions of CA3 are mainly based on plasticity of these synaptic connections, but recent work by us and others suggests that active, voltage-dependent properties of CA3PC dendrites may also promote ensemble functions. Dendritic voltage-dependent ion channels allow nonlinear amplification of spatiotemporally correlated synaptic inputs (such as those produced by ensemble activity) and can generate local dendritic spikes, which may elicit specific action potential patterns (e.g. bursts) and induce synaptic plasticity. Furthermore, dendritic processing may be modulated by activity-dependent regulation of dendritic ion channels. However, still little is known about the active properties of CA3PC dendrites and their functions during spatial coding or memory tasks.
We aim to test the hypothesis that active integration of inputs by dendrites of individual CA3PCs plays an important role in their recruitment into specific context-coding ensembles. Evidence for active dendritic integration will be studied combining in vitro (patch-clamp electrophysiology and two-photon (2P) microscopy in slices) and in vivo (2P imaging and activity-dependent labelling in behaving rodents) approaches.
The main overall objectives are the following:
Objective I. To elucidate the mechanisms, compartmentalization and plasticity of dendritic spikes underlying complex spike burst firing in CA3PCs in acute rodent brain slices;
Objective II. To elucidate the functional relevance of active dendritic integration in CA3PCs during spatial memory in vivo.
We have established an in vivo (two-photon microscope combined with virtual reality) system for imaging hippocampal neurons, and began experiments in head-fixed mice navigating in various virtual spatial contexts. We developed software tools to program data acquisition protocols and monitor behavioral performance, and worked out spatial context discrimination training paradigms.
Using novel computational and experimental approaches we investigated how long-term synaptic plasticity depends on the spatial pattern of inputs as well as local and global dendritic integrative mechanisms in hippocampal neurons.