Cells preferentially responding to visual motion in a particular direction are said to be direction-selective, and these were first identified in the primary visual cortex. Since then, direction-selective responses have been observed in the retina of several species, including mice, indicating motion analysis begins at the earliest stage of the visual hierarchy. Yet little is known about how retinal direction selectivity contributes to motion processing in the visual cortex. In this talk, I will present our experimental efforts to narrow this gap in our knowledge. To this end, we used genetic approaches to disrupt direction selectivity in the retina and mapped neuronal responses to visual motion in the visual cortex of mice using intrinsic signal optical imaging and two-photon calcium imaging. In essence, our work demonstrates that direction selectivity computed at the level of the retina causally serves to establish specialized motion responses in distinct areas of the mouse visual cortex. This finding thus compels us to revisit our notions of how the brain builds complex visual representations and underscores the importance of the processing performed in the periphery of sensory systems.

Neocortical-hippocampal interactions during off-line periods such as slow-wave sleep are implicated in memory processing. In particular, recent memory traces are replayed in hippocampus during some sharp-wave ripple (SWR) events, and these replay events are positively correlated with neocortical memory trace reactivation. A prevalent model is that SWR arise ‘spontaneously’ in CA3 and propagate recent memory ‘indices’ outward to the neocortex to enable memory consolidation there; however, the spatiotemporal distribution of neocortical activation relative to SWR is incompletely understood. We used wide-field optical imaging to study voltage and glutamate release transients in dorsal neocortex in relation to CA1 multiunit activity (MUA) and SWR of sleeping and urethane anesthetized mice. Modulation of voltage and glutamate release signals in relation to SWRs varied across superficial neocortical regions, and it was largest in posteromedial regions surrounding retrosplenial cortex (RSC), which receives strong hippocampal output connections. Activity tended to spread sequentially from more medial towards more lateral regions. Contrary to the unidirectional hypothesis, activation exhibited a continuum of timing relative to SWRs, varying from neocortex leading to neocortex lagging the SWRs (± ~250 msec). The timing continuum was correlated with the skewness of peri-SWR hippocampal MUA and with a tendency for some SWR to occur in clusters. Thus, contrary to the model in which SWRs arise spontaneously in hippocampus, neocortical activation often precedes SWRs and may thus constitute a trigger event in which neocortical information seeds associative reactivation of hippocampal ‘indices’.

My lab seeks to understand how the mammalian brain performs the computations that underlie cognitive functions, including decision-making, short-term memory, and spatial navigation, at the level of the building blocks of the nervous system, cell types and neural populations organized into circuits. We have developed methods to measure, manipulate, and analyze neural circuits across various spatial and temporal scales, including technology for virtual reality, optical imaging, optogenetics, intracellular electrophysiology, molecular sensors, and computational modeling. I will present recent work that uses large scale calcium imaging to reveal the functional organization of the mouse posterior cortex for flexible decision-making during spatial navigation in virtual reality. I will also discuss work that uses optogenetics and calcium imaging during a variety of decision-making tasks to highlight how cognitive experience and context greatly alter the cortical circuits necessary for navigation decisions.

Our research team runs several related projects studying the cellular and molecular mechanisms involved in the development of axonal connections in the brain. In particular, our aim is to uncover the principles underlying thalamocortical axonal wiring, maintenance and ultimately the rewiring of connections, through an integrated and innovative experimental programme. The development of the thalamocortical wiring requires a precise topographical sorting of its connections. Each thalamic nucleus receives specific sensory information from the environment and projects topographically to its corresponding cortical. A second level of organization is achieved within each area, where thalamocortical connections display an intra-areal topographical organization, allowing the generation of accurate spatial representations within each cortical area. Therefore, the level of organization and specificity of the thalamocortical projections is much more complex than other projection systems in the CNS. The central hypothesis of our laboratory is that thalamocortical input influences and maintains the functional architecture of the sensory cortices. We also believe that rewiring and plasticity events can be triggered by activity-dependent mechanisms in the thalamus. Three major questions are been focused in the laboratory: i) the role of spontaneous patterns of activity in thalamocortical wiring and cortical development, ii) the role of the thalamus and its connectivity in the neuroplastic cortical changes following sensory deprivation, and iii) reprogramming thalamic cells for sensory circuit restoration. Within these projects we are using several experimental programmes, these include: optical imaging, manipulation of gene expression in vivo, cell and molecular biology, biochemistry, cell culture, sensory deprivation paradigms and electrophysiology. The results derived from our investigations will contribute to our understating of how reprogramming of cortical wiring takes place following brain damage and how cortical structure is maintained.