The sense of smell is a unique sense from a neurological standpoint. It is our most direct link to the external world, and the brain regions responsible for processing smell have changed very little over evolutionary time. Some neurons in the mouse olfactory cortex — the part of the brain dedicated to interpreting smell — resemble those found in lizards or salamanders more than those in the neocortex, a region of the brain found in mammals. Unlike signals from touch, sight, hearing, or taste, which first pass through the thalamus before reaching the cortex, signals from smell bypass this intermediate region. When you smell something pleasant, like freshly baked croissants, or something unpleasant, like burnt toast, the signals from odor molecules go directly to the olfactory cortex. This direct pathway suggests that the olfactory system has a different evolutionary origin compared to other senses. The neocortex is a feature of all mammals, including mice, dogs, and humans, but not of reptiles or amphibians. Scientists are trying to understand how the neocortex evolved, as it appears very different from the brains of lizards and salamanders, making direct comparisons difficult. However, the olfactory cortex is a part of the brain that is easier to compare across species. In a study led by Alexander Fleischmann of Brown University, researchers compared the neurons in the mouse olfactory cortex, the neocortex, and the brains of reptiles and amphibians. Modern techniques in molecular biology allow scientists to study gene expression in individual cells. Each cell in an organism contains the full genome, but only a subset of genes is active at any given time. By analyzing which genes are expressed, scientists can learn about a cell's function, its developmental history, and the molecular processes it carries out. In the mouse olfactory cortex, researchers found that, while it resembles other cortical areas in some ways, it also has distinct features. The study found that neurons in the olfactory cortex change more gradually from one type to another compared to the neocortex. In the olfactory cortex, the gene expression of different neuron types forms smooth gradients, whereas in the neocortex, the differences between neuron types are more abrupt. Despite these differences, some of the gene expression patterns found in the olfactory cortex were also observed in lizards and salamanders. The study also revealed that the olfactory cortex of adult mice contains many immature neurons, similar to those found in young mice. These immature neurons may help the brain adapt to environmental changes, a process known as neural plasticity. Comparing laboratory mice, which live in stable environments, with wild mice, which experience more dynamic conditions, showed that the differences in their olfactory cortices were mainly in the activating neurons. Overall, the mouse olfactory cortex appears to have retained three key ancestral features: smooth changes in gene expression between neurons, a similarity with more distantly related species, and a higher level of cellular plasticity due to the presence of immature neurons. These findings contribute to our understanding of brain evolution and have been compiled into a resource for researchers interested in olfaction, brain evolution, and cellular decision-making.