The unique neural wiring of the human hippocampus may maximize memory

Our brain’s memory center bears a sleek design.

A peek into living tissue from human hippocampi, a brain region crucial for memory and learning, revealed relatively few cell-to-cell connections for the vast number of nerve cells. But signals sent via those sparse connections proved extremely reliable and precise, researchers report December 11 in Cell.

One seahorse-shaped hippocampus sits deep within each hemisphere of the mammalian brain. In each hippocampus’s CA3 area, humans have about 1.7 million nerve cells called pyramidal cells. This subregion is thought to be the most internally connected part of the brain in mammals.

But much information about nerve cells in this structure has come from studies in mice, which have only 110,000 pyramidal cells in each CA3 subregion.

Previously discovered differences between mouse and human hippocampi hinted that animals with more nerve cells may have fewer connections — or synapses — between them, says cellular neuroscientist Peter Jonas of the Institute of Science and Technology Austria in Klosterneuburg. To see if this held true, he and his colleagues examined tissue taken with consent from eight patients who underwent brain surgery to treat epilepsy.

Recording electrical activity from human pyramidal cells in the CA3 area suggested that about 10 synapses existed for every 800 cell pairs tested. In mice, that concentration roughly tripled. Despite the relatively scant nerve cell connections in humans, those cells showed steady and robust activity when sending signals to one another — unlike mouse pyramidal cells.

Consistent with the setup in humans, mathematical modeling suggested that an abundance of nerve cells combined with sparse but strong connections is a design that maximizes memory retrieval and storage.

Understanding the unique properties of the human hippocampus will help researchers learn more about diseases that affect memory, Jonas says. “It’s important to realize that the human brain is not a scaled, large version of the rodent brain.”