A study analyzing individual synapses in macaques and mice shows primate neurons have two to five times fewer synapses than mice in the visual cortex.

Primates are generally considered smarter than mice. But in a surprising finding, neuroscience researchers at the University of Chicago and Argonne National Laboratory have discovered that mice actually have more synapses connecting the neurons in their brains.

In a study comparing the brains of macaques and mice at the synaptic level, the researchers found that the primates had far fewer synapses per neuron compared to the rodents, in both excitatory and inhibitory neurons in layer 2/3 of the primary visual cortex. Using artificial recurrent neural network modeling, the team was further able to determine that the metabolic cost of building and maintaining synapses likely drives larger neural networks to be sparser, as seen in primates versus mouse neurons. The results were published September 14 in Cell Reports.

The research team leveraged recent advances in electron microscopy, as well as existing publicly available data sets, to compare the connectivity in both species. They chose to examine both excitatory and inhibitory synapses, as most previous research had focused on only excitatory synapses. Focusing on layer 2/3 neurons in the adult primary visual cortex made it easier to compare across species, as these neurons have distinct morphologies that are similar in both primates and mice.

After reconstructing the microscopy images and measuring the shapes of 107 macaque neurons and 81 mouse neurons, the researchers identified nearly 6,000 synapses in the macaque samples and over 9,700 synapses in the mouse samples. Upon comparing the datasets, they found that primate neurons receive two to five times fewer excitatory and inhibitory synaptic connections than similar mouse neurons.

Computer modeling considered two potential metabolic costs: the cost of the individual electrical signals sent by neurons, called action potentials, which are energetically very expensive, and the cost of building and maintaining the synapses between different cells. What they found was that as the number of neurons increased in the network, growing metabolic constraints made it more difficult to create and maintain the connections between cells, leading to a reduced density of synapses.

The results will help inform future research in both primates and mice, as well as comparisons between the two.

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