
Like Ginsu knives, new tools find multiple uses in researchers' hands. Channelrhodopsin-2 is a cation channel from algae that depolarizes neurons in the presence of blue light. Now two research groups report complementary uses for channelrhodopsin-2 in the mouse brain: Petreanu et al. report a mapping technique for long axon projections in Nature Neuroscience, and Arenkiel et al. characterize neural circuit signal processing in Neuron.
It is difficult to determine the termination of long axons that cross the brain. Using current mapping techniques, a long axon must be followed through several brain sections, and synapses can only be inferred from overlapping axons and dendrites. Using channelrhodopsin-2, Petreanu et al. mapped the projections of pyramidal neurons in the barrel cortex, which is important in whisker sensation. They targeted channelrhodopsin-2 expression to layer 2/3 pyramidal neurons by electroporating mouse embryos. When these mice reached adulthood, the authors recorded action potentials in pyramidal cells expressing channelrhodopsin-2 after they illuminated either the cell body in layer 2/3 or the axon in layer 5, suggesting that channelrhodopsin-2 is transported to axons, where it can initiate action potentials.
Pyramidal cell axons that enter the corpus callosum terminate in the cortex on the opposite (contralateral) side of the brain. The authors did whole-cell recordings in the barrel cortex contralateral to the side that was electroporated and illuminated the region surrounding the recording electrode. They recorded excitatory postsynaptic currents in neurons in layers 2/3 and 5 and more rarely in layer 6. The authors recorded excitatory postsynaptic currents in these same layers of the ipsilateral cortex, suggesting that pyramidal neurons in the barrel cortex synapse in the same cortical layers on both sides of the brain.
Unlike pyramidal cells, the connections between mitral cells in the olfactory bulb and neurons in the piriform cortex have been mapped, but the processing of signals in these structures is controversial. Are action potentials in single piriform cortex neurons caused by single mitral cells or the convergence of signals from multiple mitral cells? Arenkiel et al. drove expression of channelrhodopsin-2 in mitral cells with the Thy1 promoter. They removed the skull covering the olfactory bulb and illuminated its dorsal surface while recording from mitral cells. Mitral cells fired action potentials in response to odors or blue light. Mitral cell responses were similar when the authors illuminated narrow or wide regions of the olfactory bulb, suggesting that mitral cells are not subject to lateral inhibition.
The authors then illuminated mitral cells with narrow or broad diameter light and recorded from neurons in the piriform cortex. When they illuminated a 600
m-diameter region of the olfactory bulb, neurons in the piriform cortex consistently fired action potentials. However, 300 and 100
m-diameter illumination increased action potential firing in piriform cortex neurons to a lesser extent, suggesting that signals from multiple mitral cells converge at piriform cortex neurons.
The ability to observe signal processing in real time may provide insight into disorders, like traumatic brain injury, that disrupt the normal flow of information in the brain.
