(Figure 1: Fluorescent labeling reveals mossy fibers (red) projecting from the dentate gyrus (green) into the CA2 subregion (orange). Credit: Keigo Kohara, RIKEN–MIT Center for Neural Circuit Genetics)

Novel combination of techniques reveals new details about the neuronal networks for memory

Learning and memory are believed to occur as a result of the strengthening of synaptic connections among neurons in a brain structure called the hippocampus. The hippocampus consists of five subregions, and a circuit formed between four of these is thought to be particularly important for memory formation. Keigo Kohara and colleagues from the RIKEN–MIT Center for Neural Circuit Genetics and RIKEN BioResource Center have now identified a previously unknown circuit involving the fifth subregion.

For a hundred years, memory research has typically focused on the main circuit, which projects from layer II of the entorhinal cortex via the dentate gyrus to subregion CA3 and then CA1. Subregion CA2 lies between CA3 and CA1 but its cells are less elaborate than those of its neighbors and were thought not to receive inputs from the dentate gyrus.

Kohara and his colleagues combined anatomical, genetic and physiological techniques to analyze the connections formed by neurons in the CA2 subregion of the hippocampus in unprecedented detail. First, they identified the CA2 subregion by examining the expression of three genes that encode proteins called RGS14, PCP4 and STEP using a fluorescent marker to label nerve fibers—a technique called fluorescent immunohistochemistry. They were surprised to discover that, contrary to expectations, CA2 neurons receive extensive inputs from cells in the dentate gyrus (Fig.1).

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