Research interest: Neocortical structure, function and plasticity at the large neuronal ensembles level: from basic to pre-clinical research.

Neocortex, believed by Neuroscientists to be the hallmark of brain evolution, is still poorly understood and therefore constitutes a major challenge for Neuroscientists. This challenge calls for an innovative combination of new concepts about cortical function combined with state-of-the-art technologies.
For our basic research, our approach aims to unravel the functional organization of neocortex at the level of large evoked ensembles of many thousands of active, interacting neurons – a level of neocortical functional organization known as the ‘mesoscopic’ level. These large ensembles have been functionally imaged, verified by microelectrode arrays, and were found to be supported by long-range horizontal axonal projections within neocortical gray matter, suggesting a novel unification of structure and function at the neocortical mesoscopic level. Our working hypothesis is that such mesoscopic neuronal ensemble, found in many neocortical locations and in many mammalian cortices, constitute the most fundamental motif of neocortical function and that the integrative activity of such ensembles underpins perception, learning and memory, and behavior. Strong plasticity of such ensembles has been revealed when rodents were transferred from their impoverished, small cage to a novel environment that imitates their natural environment (our ‘naturalistic habitat’).
Our preclinical research has elucidated how such ensembles and their interactions with neocortical blood circulation could be harnessed to protect the neocortex from injury. This is the case of ischemic stroke injury in a rodent model, where injury can be avoided by employing protective sensory stimulation (a case of a novel neurovascular plasticity).
At the technical level we employ a state-of-the-art battery of complementary techniques to study neuronal ensembles. These include high resolution functional imaging that are tailored to study the mesoscopic level (a novel high-resolution fast intrinsic signal optical imaging, voltage-sensitive dyes optical imaging, and the novel functional ultrasound imaging enabling high resolution functional imaging from the entire rodent brain); optogentic-based neocortical mapping by laser photostimulation; large microelectrode arrays; blood-flow imaging (laser speckle imaging, Doppler optical coherence tomography, functional ultrasound imaging); spectroscopy; AAV virus-based tract tracing of axonal projections; pharmacological and histological manipulations; and behavioral analysis.
Our animal model is the rodent neocortex. While most of our research has targeted sensory neocortex (especially the ‘barrel cortex’ subdivision of the somatosensory cortex where the rodent’s whiskers are represented) in the anesthetized rodent, we are now expanding to employ our techniques to study the entire neocortex in the awake rodent. We are also currently expanding our studies on caged vs. naturalistic habitat rodents by building a ‘rodent paradise’; continue with extensive studies to reveal the mechanisms underlying ischemic stroke protection by sensory stimulation; and further studying the relationship between large neuronal ensembles and their relationship with blood flow, perception, learning and behavior in young adults and old rodents.