Researchers from the INCLIVA Psychiatry and Neurodegenerative Diseases research group and the University of Valencia have shown that the structure and connectivity of interneurons in the adult brain, the communication bridge between neurons, can be changed.
The results of the research, led by Juan Nácher Roselló, senior professor at the Department of Cellular Biology, Functional Biology, and Physical Anthropology at the University of Valencia, was published in the international journal Frontiers in Cellular Neuroscience this June.
Dr. Nácher explained that “although we have traditionally had a static view of the adult brain, we have known for decades that neurons are capable of modifying their structure and connections to adapt to a changing environment and to perform cognitive functions such as learning or memory tasks. The connections between neurons are made largely through structures called dendritic spines. These spines and the connections they mediate appear and disappear depending on the neuronal activity present and are influenced by different events such as stress and other adverse experiences”.
Until now the study of how the structure of dendritic spines (and consequently that of neuronal connections) change in the adult brain was limited to spines found in excitatory neurons, the ones mainly responsible for the essential communication pathways in our brain. In turn, the functioning of excitatory neurons is regulated by inhibitory neurons, or interneurons, which synchronize them and integrate them into local circuits.
“Our research aimed to determine if the dendritic spines of interneurons, and consequently their connections, are also dynamic and therefore capable of changing”, said Juan Nácher.
“We have observed the emergence and disappearance of these spines with the help of transgenic mice that have fluorescent interneurons”, he said. To stimulate these events the researchers used glutamate, a molecule that interferes in the communication between neurons and which acts as a neurotransmitter released by the emitting neuron which is captured by the receptor neuron, usually in a dendritic spine.
“We chose glutamate because specific NMDA-type receptors involved in memory formation participate in its uptake. We used compound MK801 to block the binding of glutamate to this receptor in the interneurons of our mice. This blockade resulted in changes in the anxiety and locomotion of these animals, which confirmed its effect on their brains”, he explained. “In addition, the administration of MK801 rapidly decreased the rate of appearance of new dendritic spines and the density of these spines in interneurons”, he added.
“Our results show the ability to change the structure and connectivity of interneurons in the adult brain and the important influence of NMDA receptors in this process”, he concluded.
For Dr. Nácher, the results are especially interesting because alterations in these receptors and in interneurons have been found in different psychiatric diseases such as schizophrenia. Their finding opens the doors to the development of possible therapeutic routes against these types of diseases.