Towards complete structural and functional imaging of cortical circuits
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1
Harvard Medical School, United States
For the past six years, our lab has been using two-photon calcium imaging to measure the in vivo physiological activity of virtually every neuron (up to several thousand) in volumes of visual cortex spanning up to several hundred mm (Ohki et al., 2005, 2006). More recently, we have scaled up the collection of serial-section electron microscopic images so we can measure the fine anatomical structure of similarly large volumes of cortical tissue. By combining these two methods, we hope to collect data sets that provide a complete physiological and structural overview of a specific piece of the cortex.
Because we are interested in large cortical volumes at high resolution, we have concentrated on very high throughput. To reconstruct the finest axons, dendrites, and synapses with electron microscopy, pixels must be on the order of <5 nm and section thickness should be at most 40 nm. At this resolution, reconstruction of a 100 mm cube requires at least 1012 bytes of data (one terabyte). A 500 mm cube would require 125 terabytes. Our first large data set consists of ~1,200 neurons in a volume that spans roughly 450 x 350 x 50 µm of cortical tissue, which is large enough to trace many of the connections between neurons within the volume. We have also studied the physiological properties of a small fraction of the cells in this volume and solved the correspondence problem between the physiological and anatomical data sets. We can point to cell bodies, axons, and dendrites within the volume and correlate their morphology and connections with the visual physiology as determined by calcium imaging.
As with many large-scale datasets, such as the genome, these anatomical data will never be fully analyzed. Instead, they will serve as a repository-an infinite slide box-of anatomical information that can answer specific well-posed questions. For any given question, only a tiny fraction of the data need be analyzed, but the completeness of the data provides a number of unique opportunities. Our lab is addressing one class of questions: are there sub-networks within the local circuit that process distinct information? If a circuit is made up of red, green, yellow and blue cells (representing a functional property such as orientation selectivity), are the red cells connected to the red cells? More generally, are intracortical connections specific, where specificity is defined as “making sense” in a functional context? This question can be posed for the multiple types of connections within a cortical circuit: between excitatory neurons within layers and between layers; and those involving the multiple types of inhibitory neurons.
Conference:
Computational and Systems Neuroscience 2010, Salt Lake City, UT, United States, 25 Feb - 2 Mar, 2010.
Presentation Type:
Oral Presentation
Topic:
Oral presentations
Citation:
Reid
R
(2010). Towards complete structural and functional imaging of cortical circuits.
Front. Neurosci.
Conference Abstract:
Computational and Systems Neuroscience 2010.
doi: 10.3389/conf.fnins.2010.03.00001
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Received:
17 Feb 2010;
Published Online:
17 Feb 2010.
*
Correspondence:
R. Clay Reid, Harvard Medical School, Boston, United States, REID@HMS.HARVARD.EDU