The synaptic basis of learning and attention

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Animals are remarkably adept at flexibly adapting their behaviour, and this ability isessential for survival in an ever-changing environment. During learning (over days),and attention (over seconds), neurons change their response properties, sharpeningtheir responses to relevant features of the environment. This plasticity depends onchanges in the tens of thousands of excitatory synapses and several thousandinhibitory synapses present on each neuron. Changes in individual synapses duringlearning are challenging to study. Even when average changes in synaptic propertiesare known, it is not straightforward to relate then to the changes in the properties ofindividual neurons as they function in a network. Thus, it remains poorly understoodwhether learning relies on changes in a small number of strong synapses, or morewidely distributed changes across a large number of synapses. Are synaptic changesclustered, to drive non-linear dendritic events? Are most synaptic changes duringlearning and attention top-down (in apical dendrites) or bottom up (in basal dendrites),or is there transfer across these domains over days? This project will address thesequestions by measuring activity in individual synaptic spines using multi-day in-vivotwo-photon calcium imaging in visual cortex as mice learn a visual discrimination taskand subsequently perform an attention-switching task (Poort... Khan et al 2022). Thesetechniques are already established and routinely used in the host lab. We will use amultidisciplinary approach, including optogenetics, imaging GCaMP7f fused with PSD-95 Fingrs and gephyrin-Fingrs, and computational modeling. The activity of individualspines will be related the activity of the soma of the same neurons and the mousebehaviour. Finally, we will investigate how the local balance of excitatory andinhibitory synapses on short stretches of dendrites is modified and how this relates toplasticity in cortical neurons (Grillo... Burrone et al Neuron 2018).