Feb 19, 2026
3 min read
Physical, social, and psychological stimulation during childhood and adolescence is critical to cognitive development.A recent study in mice suggests a molecular mechanism linking the environment to brain plasticity.
For decades, we've known that growing up in an environment rich in sensory, social, and physical stimulation promotes cognitive development and learning.Although these benefits are particularly important during childhood and adolescence, they are not limited to the early stages of life.Even in old age, a stimulating environment helps delay cognitive decline and keep the mind active.
Despite this behavioral evidence, we know very little about the underlying neural and molecular mechanisms.How does the brain translate environmental experience into lasting changes in learning ability and memory?
From the Institute of Neurosciences, a joint center of the Higher Council for Scientific Research (CSIC) and Miguel Hernández University (UMH) in Elche, we recently published in Nature Communications a study carried out on mice that provides new fundamental evidence of this process.
In particular, it shows that the influence of the environment is not uniform on all neuronal populations in the brain.In addition, it identifies one of its components, the AP-1 protein complex, as a central mediator between environment and cognition.
Three environments, three different brains
To study how the environment modulates cognition, our team, led by Dr. Ángel Barco, young female mice were raised for three months in three well defined environmental conditions.
The first group lived in an enriched environment.The animals shared large enclosures that allowed exploration and communication in groups of 15 to 20 individuals.In addition, they had training wheels and toys that were replaced regularly to maintain novelty.A second group lived in a standard environment, in small groups of 4-5 mice, with basic nesting material as the only resource.The third group grew up in an impoverished environment, characterized by social isolation and a total lack of stimulation.
After this period, the animals were tested for learning and memory.Rats from the enriched environment clearly showed better cognitive performance.This improvement was observed, for example, in the fear conditioning test, a rat version of Pavlovian classical conditioning.
In contrast, mice raised in reduced conditions had memory difficulties.Deficits were found in object recognition tests, which assess the animal's ability to distinguish a previously studied object from a new one.
Unraveling the complexity of brain cells
Understanding what happens at the molecular level in the brain is particularly complex, because dozens of neuronal and non-neuronal types coexist and interact with each other.Global analyzes combine signals from different cells, making the results difficult to interpret.To overcome this limitation, we decided to focus our research on two hippocampal neuronal populations that are essential for memory: pyramidal neurons and granule neurons.
On the one hand, we carefully divide certain regions of the hippocampus.On the other hand, we used a genetic engineering to address the neurons of interest.The combination of both methods allowed us to accurately isolate pyramidal and granule neurons.Therefore, we are able to use advanced genetic techniques to see how genes are turned on or off in each type of neuron.
One of the most striking findings of the study was that different environments did not affect the same neuronal populations in the same way.The enriched environment produced more pronounced molecular changes in the granule neurons, while the poor environment affected the pyramidal neurons more.
AP-1 as a key player in environmentally induced plasticity
In addition, the authors identified a molecular pattern that linked these changes in neurons to behavior: the two environmental conditions produced opposite effects on the AP-1 protein complex, which is responsible for regulating key genes for synaptic plasticity, that is, the ability of neurons to change their connections in response to experience.While the enriched environment activated AP-1, the poor environment suppressed it.This close correlation between AP-1 activity and cognitive performance suggested that the complex acts as a molecular translator of environmental experience.
Next, we tested whether AP-1 is required for environmentally induced memory changes. To this end, we disabled the Fos gene, which encodes a key subunit of the AP-1 complex. Doing so significantly diminished the cognitive benefits of an enriched environment.This experiment shows that without AP-1 activation, even stimulus-rich environments lose much of their ability to enhance cognition.
Thus, AP-1 acts as a key molecular translator of environmental effects on the brain.It activates genes that modify synapses and rearrange circuits, processes fundamental to learning and memory.
Turn experience into a clinical tool
These findings support the idea that physical, social and intellectual stimuli in childhood and adolescence are crucial for cognitive development.
Identifying AP-1 as a central regulator of this process opens the door to therapeutics that can be tailored or enhance the benefits of an enriched environment.Pharmacologically modulating this signaling pathway has the potential to open up new therapeutic opportunities in the future.Its application may help in the treatment of developmental brain disorders, age-related memory loss, or conditions of limited access to a stimulating environment.
Understanding how our environment "talks" to our genes is an important step in improving mental health.
