Chasing engrams in a µStim-based systems memory consolidation paradigm

In this project, we will continue investigating the principles of systems memory consolidation in a microstimulation (µStim) detection task in mice that we showed in the first round involved the formation and consolidation of memory engrams in the neocortex dependent on input from the medial temporal lobe (hippocampus and perirhinal cortex). We hypothesize that µStim-learning involves the gating of top-down inputs to layer 1 of the stimulated neocortical column. In this proposal, we will use state-of-the-art methods to record activity from the whole cortical column simultaneously using NeuroPixels electrode arrays that can record 100s of single units in the depth of the cortex as well as 2-photon imaging through a chronically inserted prism allowing side-on imaging of the whole cortical column. We will use these methods to track the evolution of memory engrams over 3 days of learning and the contribution of dendritic activity. We will also investigate a new phenomenon for which we obtained preliminary evidence in the first round. This phenomenon appears to be a neocortical analog of the recently discovered one-shot recruitment of place cells in CA1 called behavioral timescale synaptic plasticity (BTSP). In the last part of the project, we will develop (in collaboration with Service Project C02) a floating-platform behavioral paradigm based on a 5-arm maze approached used in humans in Project B05 allowing the exploration of the effect of the anesthetic propofol in head-fixed mice with state-of-the-art methodologies such as 2-photon imaging. View A04’s Video on YouTube here

Image Cortical pyramidal neurons. Courtesy of Matthew Larkum and Mostafa Abdelhamid

Archive – A04 (SFB1315/1)