development of in vivo multiphoton microscopy in primates for studying computations in cortical microcolumns
The mammalian neocortex is a circuit of amazing complexity made up from 20 billion neurons interconnected with 100 trillion connections housing our sensory, motor and cognitive computations. The hope is that there are underlying rules that govern this apparent complexity and understanding these rules would provide an obvious strategy to understand how the cortex works . Almost one century ago, anatomists discovered a remarkable order in how the cortex is organized: the presence of cords of cells oriented orthogonal to the cortical surface. These microcolumns have been hypothesized to be the fundamental computational unit from which the cortex is constructed, analogous to transistors in computers . Thus, understanding the computations that a microcolumn performs is critical for understanding how the brain works. Unfortunately however, because of technical limitations, despite five decades of intense research, it has not been possible to understand the functional organization of microcolumns. In order to do so it is essential to record simultaneously from the neurons that belongs to a single microcolumn in vivo during different behavioral tasks. To date, no technology exists that allows us to do so. To this end, we propose developing in vivo fast random- access multi-photon (RAMP) microscopy using acoustooptical deflectors combined with multielectrode recording in awake, behaving non-human primates to study the functional organization of microcolumns. Primates are ideal for these studies since this is where microcolumns are most conspicuous. This new met hod will enable sampling rates of up to so KHz over any three-dimensional predetermined scanning path and thus will allow for the first time fast imaging along cortical depth in order to image microcolumns. Simultaneous multielectrode recordings will enable us to also record the spiking activity of many neurons belonging to a single microcolumn. Understanding the functional organization of microcolumns could also provide a novel way to approach a number of diseases such as autism, Down's syndrome and schizophrenia where differences in the organization of microcolumns have been observed.
Arnold O. Beckman exemplifies the meaning of the word humanitarian. Combined with his unwavering enthusiasm for life, his keen sense of humor and his strong moral and ethical principles, he is a national icon.