Honing in on the hippocampus

Reconstructing neural connections in the human hippocampus in three dimensions could improve computational models of brain and our understanding of disease.
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Three dimensional view of the connections between neurons in the human hippocampus. Excitatory synapses are shown in green and inhibitory synapses are shown in red. Image credit: Montero-Crespo et al. (CC BY 4.0)

There are billions of nerve cells or neurons in the human brain, and each one can form thousands of connections, also called synapses, with other neurons. That means there are trillions of synapses in the brain that keep information flowing.

Studying the arrangement of individual neurons in the human brain, and the connections between them, is incredibly difficult because of its complexity. Scientists have tools that can image the whole brain and can measure the activity in different regions, but these tools only visualize brain structures that are large enough to be seen with human eyes. Synapses are much smaller (in the range of nanometers), and can only be seen using thin slices of preserved brain tissue through a technique called electron microscopy.

The hippocampus is a part of the human brain that is critical for memory, learning and spatial orientation, and is affected in epilepsy and Alzheimer’s disease. Although numerous studies of the hippocampus have been performed in laboratory animals, such as mice, the question remains as to how much of the information gained from these studies applies to humans. Thus, studying the human brain directly is a major goal in neuroscience. However, the scarcity of human brain tissue suitable for the study of synapses is one of the most important issues to overcome. Fortunately, healthy human brain tissue that can be studied using electron microscopy is sometimes donated after death. Using these donations could improve the understanding of the synapses in normal brains and possible changes associated with disease.

Now, Montero-Crespo et al. have mapped synapses in the normal human hippocampus in three dimensions – providing the first detailed description of synaptic structure in this part of the brain. Using high-powered electron microscopes and donated brain tissue samples collected after death, Montero-Crespo et al. imaged almost 25,000 connections between neurons. The analysis showed that synapses were more densely packed in some layers of the hippocampus than in others. Most synapses were found to be connected to tiny dendritic ‘spines’ that sprout from dendritic branches of the neuron, and they activated (not suppressed) the next neuron.

Beyond its implications for better understanding of brain health and disease, this work could also advance computer modelling attempts to mimic the structure of the brain and its activity.