The sense of smell is a unique sense from a cerebral perspective. It is our most direct link with the external world and has changed very little during evolution. Signals from touch, sight, hearing, and taste first pass through a brain region called the thalamus before reaching their specific areas in the cortex. In contrast, when you smell something pleasant, like fresh-baked croissants, or something unpleasant, like burnt toast, the signals from odor molecules go directly to the brain's olfactory cortex without passing through the thalamus. This direct connection is special, and from an evolutionary point of view, the sense of smell is a very ancient way of learning about our environment. The sense of smell is widespread among animals, which means that we can compare animal brains to learn more about the origins of our own brain.
When we think of the brain, we usually think of the neocortex. This is the part of the brain that has significantly developed in humans and other primates. It is considered essential for understanding "advanced" characteristics like consciousness, intelligence, or language. The neocortex is found in all mammals, such as mice, dogs, and humans, but not in reptiles or amphibians. So, where did the neocortex come from? How has it evolved? For scientists, this is a puzzle with many known pieces and many missing ones. One of the missing pieces is that the neocortex appears very different from the brains of lizards and salamanders, making direct comparison difficult. However, humans and mice have other parts of the brain that are easier to compare with lizards and salamanders, such as the olfactory cortex.
In collaboration with Sara Zeppilli, Alexander Fleischmann (Brown University, United States), and other researchers, a team has worked to add a piece to this puzzle by comparing the neurons of the mouse olfactory cortex, those of its neocortex, and those of the brains of reptiles and amphibians. The analysis of neurons at the molecular level is a powerful way to better understand the brain. Experimental technologies have advanced significantly in recent years, allowing scientists to systematically determine the levels of expression of all genes for each cell of a given tissue. The level of expression of a gene indicates how necessary it is in a given cell. For example, in a mouse, each cell has the full set of genes, but only a subset is needed for the cell to perform its function. This information helps scientists understand the state of the cell, the decisions it has made, or the molecular functions it performs.
By examining the neurons in the olfactory cortex, researchers found that, in many ways, the olfactory cortex resembled other cortical areas but had some marked differences. Focusing on neurons, they identified the usual cell types found in the mouse cortex, such as different types of excitatory and inhibitory neurons. In examining these neurons, they discovered that the types of excitatory neurons change more gradually from one type to another in the olfactory cortex than in the neocortex. The types of olfactory neuronal cells seem to form smooth gene expression gradients, while the types of neocortical neurons are more clearly distinct and have more abrupt changes in expression between them.
This discovery led to an important evolutionary question: are the neurons of the olfactory cortex closer to other brain regions of the mouse or do they resemble more the neurons of other non-mammalian species? The answer proved surprising. The types of neurons in the mouse olfactory cortex resemble those of lizards or salamanders more than those of the mouse neocortex. This is remarkable because, for 200 million years, the olfactory cortex neurons of the mouse have evolved alongside those of the mouse neocortex.
The team also found a large number of immature neuron types in the adult mouse olfactory cortex. Using machine learning, they predicted that these immature neurons are destined to become excitatory neurons during the mouse's life. They hypothesized that these neurons play a role in brain plasticity, helping mice adapt their neural circuits to changes in their environment. For example, they might help mice detect new odors. Comparing the results from laboratory mice, living in a monotonous environment, with those of wild mice living in a more dynamic environment, they found that the main differences between the two groups' olfactory cortices were at the level of excitatory neurons.
Combining these results, the mouse olfactory cortex seems to have retained three ancestral molecular characteristics: gradual changes in gene expression between excitatory neurons, marked similarity with evolutionarily distant species, and increased cellular plasticity due to the presence of a pool of immature neurons. This study provides a valuable resource for researchers interested in olfaction, brain evolution, and cellular decision-making. For the researchers, it is a fundamental study on which they are building new projects, such as a study aimed at understanding how the cells of the olfactory cortex modify their gene expression in response to learning a new odor. Through the sense of smell, they have added a piece to the puzzle that constitutes the evolution of the brain.
Olfactory Cortex Shows Ancient Neural Traits in Mammals
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