Goals and strategy
From a single synapse to simple behaviors, the nervous system exhibits rich and complex dynamics that convey every perception we experience and every action we make. In particular, extracting regularities in the environment to build predictions of forthcoming sensory percepts is an essential cognitive process, which animals use to adjust their behavior and achieve specific goals. Perceptual predictions originate from an internal representation of the world in the brain that is continuously shaped by new experiences and can bias behavior.
Recent developments of genetically-encoded sensors and effectors along with novel behavioral paradigms have positioned mice as an ideal model to address these questions. In the laboratory, we study the existence and influence of experience-dependent internal representations on sensory processing and perceptual decision-making in mice performing visuo-tactile multisensory tasks. Our lab uses a combination of in vivo electrophysiology, wide-field imaging, two-photon microscopy, mouse behavior and molecular biology to address this question.
Imaging cortical circuits during behaviors
In order to understand how the brain can learn and execute perceptual decision-making tasks, we need to characterize key neuronal pathways involved in processing sensory information used to drive behavior. Monitoring neuronal activity from large cortical regions down to local microcircuits will help understand how information flows across different brain regions and what computation neuronal networks in these areas perform.
In particular, we use two-photon imaging through cranial windows to study the local microcircuit computation. In order to image neuronal responses in all layers simultaneously, we use microprisms inserted in the cortex. This movie shows a population of neurons imaged across all cortical layers in a mouse primary somatosensory cortex during the performance of a whisker-based discrimination task.
Tracking synaptic integration in single-neurons dendrites
Individual pyramidal neurons in the cortex form synapses on their dendrites with thousands of pre-synaptic partners. Dendritic calcium imaging can be used as a proxy to characterize individual synaptic input through NMDAR-dependent calcium influx in compartmentally isolated spines. We focus on the emergence of new sensorimotor representations in pyramidal neurons receiving synaptic inputs coming from diverse sensory modalities.
Single-neuron gene delivery is achieved through two-photon targeted single-cell electroporation in identified brain regions. This movie shows a stretch of dendrite in the primary visual cortex of mouse exposed to visual stimuli. This dendrite expressed a red fluorescent protein (mRuby2) and a genetically-encoded calcium indicator (GCaMP6s) to track individual synaptic inputs.
Mechanisms of synaptic plasticity underlying learning
A fundamental hypothesis in neuroscience asserts that long-lasting memories are formed and maintained through activity-dependent changes in synaptic transmission. Structural and functional plasticity occur constantly in vivo and is strongly enhanced with new sensory experience. However task-induced structural plasticity of functionally-identified spines has not been reported yet.
We target single-neurons in the cortex and study their integrative properties over the course of learning. We investigate the molecular mechanisms responsible for synaptic plasticity through protein tracking and gene manipulation in single-neuron in vivo. This image shows a stretch of dendrite in vivo where AMPA receptors are labelled in green. Spine volume and AMPAR density can be used to measure task-induced plasticity.