Editors' ChoiceNeuroscience

Dissecting Function in the Living Brain

Sci. Signal.  04 Mar 2008:
Vol. 1, Issue 9, pp. ec87
DOI: 10.1126/stke.19ec87

Because the brain is composed of many interconnected cell types in close proximity, it is not easy to determine the precise function of any one class. Existing methods such as lesions or pharmacological inhibition are relatively crude, and their effects cannot reliably be used to eliminate the contribution of one cell type. Even genetic approaches, which can be targeted to certain cells, have only been used to inhibit one receptor subtype, and the deficits are often present throughout development, confounding interpretation. Nakashiba et al. constructed a tetanus-toxin-based triple transgenic mouse that allows reversible inhibition of all the synaptic activity of one type of cell in the hippocampus, the CA3 pyramidal cell. When the CA3 hippocampal cells were silenced, the rats could still learn a spatial task but could not recall certain memories or perform rapid learning tasks.

T. Nakashiba, J. Z. Young, T. J. McHugh, D. L. Buhl, S. Tonegawa, Transgenic inhibition of synaptic transmission reveals role of CA3 output in hippocampal learning. Science 319, 1260-1264 (2008). [Abstract] [Full Text]