The synaptic basis of learning and attention

Animals are remarkably adept at flexibly adapting their behaviour, and this ability is
essential for survival in an ever-changing environment. During learning (over days),
and attention (over seconds), neurons change their response properties, sharpening
their responses to relevant features of the environment. This plasticity depends on
changes in the tens of thousands of excitatory synapses and several thousand
inhibitory synapses present on each neuron. Changes in individual synapses during
learning are challenging to study. Even when average changes in synaptic properties
are known, it is not straightforward to relate then to the changes in the properties of
individual neurons as they function in a network. Thus, it remains poorly understood
whether learning relies on changes in a small number of strong synapses, or more
widely distributed changes across a large number of synapses. Are synaptic changes
clustered, to drive non-linear dendritic events? Are most synaptic changes during
learning 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 these
questions by measuring activity in individual synaptic spines using multi-day in-vivo
two-photon calcium imaging in visual cortex as mice learn a visual discrimination task
and subsequently perform an attention-switching task (Poort... Khan et al 2022). These
techniques are already established and routinely used in the host lab. We will use a
multidisciplinary approach, including optogenetics, imaging GCaMP7f fused with PSD-
95 Fingrs and gephyrin-Fingrs, and computational modeling. The activity of individual
spines will be related the activity of the soma of the same neurons and the mouse
behaviour. Finally, we will investigate how the local balance of excitatory and
inhibitory synapses on short stretches of dendrites is modified and how this relates to
plasticity in cortical neurons (Grillo... Burrone et al Neuron 2018).