The mammalian neocortex is instrumental in a variety of cognitive functions, and understanding cortical circuitry is essential for prevention and treatment of mental disorders. A prominent feature of the cortex is that neurons with similar functional properties are organized in columns. However, how the columnar structure arises during development remains poorly understood. Our recent study in mouse visual cortex has shown that sister neurons originating from a common progenitor cell during early brain development exhibit strong similarity in orientation tuning, arguably the most important functional property in the primary visual cortex. This finding demonstrated, for the first time, a direct correspondence between the ontogenetic and functional columns, and it opened new avenues for studying cortical circuitry. The proposed study aims to address several basic questions concerning the developmental origin of cortical microcircuits, using a combination of techniques including two-photon imaging, electrophysiological recording, neuronal labeling, and molecular perturbation with recombinant viral vectors. By testing whether and how the functional similarity between sister neurons depends on their lineage and physical distances, we will define the basic processing unit of the cortex (Aim 1). By manipulating the excitability and NMDA receptor expression in selected neurons and visual experience of the animal, we will elucidate the interactions between developmental lineage, electrical activity, and visual experience in shaping the functional properties of cortical neurons (Aims 2 and 3). Finally, using high-speed circuit mapping with glutamate uncaging, we will detect common inputs to clonally related sister neurons in order to understand the synaptic basis for their functional similarity. These experiments represent a major step to bridge developmental and systems neuroscience, and they are likely to provide unprecedented insights into the development and organizational principle of cortical microcircuits.
Understanding the functional organization of the mammalian neocortex and how it is constructed during development is essential for developing therapeutic approaches for treating neurological disorders. For example, strabismus and amblyopia are developmental disorders associated with deficits in visual cortical processing, and schizophrenia and autism have been linked to abnormal development of other cortical areas. Our study aims at understanding how columnar organization, a fundamental feature of the neocortex, is shaped by developmental lineage, electrical activity, and visual experience. The insights gained from these studies should have important implications for the treatment and prevention of visual impairment and a variety of other brain disorders.
|Bochner, David N; Sapp, Richard W; Adelson, Jaimie D et al. (2014) Blocking PirB up-regulates spines and functional synapses to unlock visual cortical plasticity and facilitate recovery from amblyopia. Sci Transl Med 6:258ra140|
|Zhang, Siyu; Xu, Min; Kamigaki, Tsukasa et al. (2014) Selective attention. Long-range and local circuits for top-down modulation of visual cortex processing. Science 345:660-5|
|Hang, Giao B; Dan, Yang (2011) Asymmetric temporal integration of layer 4 and layer 2/3 inputs in visual cortex. J Neurophysiol 105:347-55|
|Bavelier, Daphne; Levi, Dennis M; Li, Roger W et al. (2010) Removing brakes on adult brain plasticity: from molecular to behavioral interventions. J Neurosci 30:14964-71|
|Alitto, Henry J; Dan, Yang (2010) Function of inhibition in visual cortical processing. Curr Opin Neurobiol 20:340-6|
|Li, Cheng-Yu T; Poo, Mu-Ming; Dan, Yang (2009) Burst spiking of a single cortical neuron modifies global brain state. Science 324:643-6|