Unambiguous Determination of the Direct Inputs to a Single Neuron

Identifying neural circuits and figuring out how they process signals has been a prominent approach in attempts to understand how the brain works. However, the clear identification of neural circuit components is nearly always impossible. Even when a particular neuron is indisputably identified the rest of the circuit may usually only be guessed at using neural anatomical principles gained over the past century. A new technique reported in the paper “Targeting Single Neuronal Networks for Gene Expression and Cell Labeling In Vivo” (published August 26, 2010 in Neuron) may go a long way towards changing this situation.

Using the new technique, a single living neuron and the neurons that form synapses onto it may be unambiguously labeled. This is accomplished in part by using a modified virus that spreads from the original infected neuron through synapses to the neurons that formed the synapses. The first neuron is infected using a technique called electroporation. The virus only moves backwards (retrograde) and only crosses one synapse. The virus does not cross the infected neuron’s synapses onto other cells.

The labels depend on what are put into the genes. The electroporated neurons in this paper were labeled with yellow florescence while the neuron’s that synapse onto them were labeled with red florescence. One alternative labeling scheme suggested in the paper would be to use Brainbow labeling of the monosynaptically connected neurons so the synapses may be identified by color. (Brainbow labeling would cause each neuron to have a distinct randomly expressed florescent color.) Wouldn’t this be exciting while recording the electrical activity of the labeled neurons?

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