The brain activity map project and the challenge of functional connectomics

Abstract

The function of neural circuits is an emergent property that arises from the coordinated activity of large numbers of neurons. To capture this, we propose launching a large-scale, international public effort, the Brain Activity Map Project, aimed at reconstructing the full record of neural activity across complete neural circuits. This technological challenge could prove to be an invaluable step toward understanding fundamental and pathological brain processes.

Figure 1. Large-Scale Calcium Imaging of Neuronal Activity

(A) Living brain slice from primary visual cortex of a mouse stained with the calcium indicator fura-2 AM. More than a thousand neurons are labeled and can be imaged with a two-photon microscope. From Yuste et al. (2011). (B) The calcium concentration in the soma of a neuron (bottom) faithfully tracks the electrical firing pattern of the cell (top). From Smetters et al. (1999). (C) Reconstructed “raster plot” of the spontaneous spiking activity of 754 cells from a similar experiment. From Cossart et al., 2003.

Figure 2. Nanoprobes, Wireless, and Synthetic Biology Technologies for the BAM Project

(Left) Silicon nanoprobe arrays (after Du et al., 2009b). (A) Flip-chip assembly scheme for connecting the silicon devices with printed circuit boards. (B) SEM micrograph of the rear section of a 50-μm-thick shaft array showing the multilayer stacked structure. Adjacent layers have a spacing of 100 μm, which is set by the thickness of the flexible cable. (C) Side view of the 50-μm-thick shaft array showing that the shafts are stress balanced and are able to retain approximately constant relative spacing. (Right) Synthetic biology approaches. (D) A voltage sensitive calcium channel influences the error rate of an engineered DNA polymerase. X marks sites of mismatch between “T” in the template strand (lower) and “G” new copy strand. Note scale of the various devices and cells.