Journal Club : Rodent Secondary Somatosensory Cortex SII

Who were the primary developers of two-photon microscopy for visualizing brain activity?  Following Watt Webb’s seminal work, it was Winfried Denk, David Tank, Karel Svoboda, and David Kleinfeld. What do these four have in common?  They all worked at Bell Labs, and they all do imaging in rodent somatosensory cortex.  Primary somatosensory cortex (SI), particularly barrel cortex has many advantages. You can directly observe the input (whisker touching), you can get behavioral output, the cortex is smooth, has a vivid characteristic pattern of cytochrome oxidase staining and is accessible to a cortical window. Consequently, SI is one of the best characterized regions of cortex.  Far less understood is the structure and function of secondary somatosensory cortex (SII), but it likely plays an essential role in rodent sensory perception. For Journal Club #3, I review what is know of the location, structure, connectivity, physiology and function of SII.

Mice aren’t that blind

Just saw a cool informal talk from Andreas Burkhalter about the mouse visual cortex.  He has a fascinating paper, Area Map of Mouse Visual Cortex, in the Journal of Comparative Neurology, in which he identifies not just three or four areas of mouse visual cortex, but twelve! Each area has a complete map of the entire visual field.  He combines triplet injections of Di-I, Di-O and BDA as fiducial markers with a label for callosal connections. He fixes the tissue in a manner that allows the unrolling and flattening of the entire mouse cortex. This allows him to segment and show the orientation of each field in a single cortical layer in the same slice. Different layers give different patterns of projection. Given the richness of the data obtained, I’m surprised that more systems neuroscientists don’t use identical techniques.

Triple labeling of mouse visual cortex

He has also created a wiring diagram of each of these and shown that receptive field size increases with the depth in the visual system hierarchy. He also noted that although Michael Stryker finds 50% of visual cortex neurons are direction selection (when stimulated by drifting gratings), he finds only 10% are direction selective when using random dot patterns. Presumably, drifting gratings provide additional cues beyond direction of motion that confound analysis. For such a ‘blind’ creature, mice sure have a complex pattern of circuitry to process visual information.

Brainbow mice are out

Jeff Lichtman‘s Brainbow mouse paper is out! Not that I really need to report that news, as it is, of course, on the cover of Nature. Jean Livet comes up with some really clever genetic strategies involving incompatible, overlapping Lox sites to generate random, combinatorial patterns of multiple fluorescent proteins inside the cell. Around 90 different shades can be discerned by spectral deconvolution.

Besides making pretty covers, why is this so cool?

Well, this technique provides a method for generating high resolution maps of the brain. With a single fluorescent tag, the processes of neighboring cells blur together and became impossible to trace unambiguously. With brainbow, many neighboring axons are clearly resolvable. This is the perfect genetic tool to use for a large-scale, all-out effort for the complete mapping of the circuitry of the mouse brain. It would be a tremendous challenge, but perhaps no more difficult than the human genome project. A large public consortium, or a Celera of the brain can really attack the connectivity problem now.

Of course, there still is the more difficult problem of showing the functional connectivity of the circuit map. Then again, this technique isn’t limited to swapping in static fluorescent tags. The insert cassette could be doped with a single FP functional indicator like G-CaMP2… Would this allow the combination of static circuit mapping with functional testing?