Variations to the Kirrel3 gene are known to be associated with intellectual disability, autism, and Jacobsen syndrome, a rare developmental disorder that often includes intellectual disabilities. Because of this strong association, the research team investigated how changes to Kirrel3 impair brain circuits critical for memory and learning.

Any cognitive task, from learning a new skill, having a conversation or driving to work requires the neurons of our brains to talk to each other. They are linked by connections called synapses that transmit these messages from one neuron to the next. Each neuron makes multiple synapses allowing it to send and receive information to many neurons within a large network.

The study shows that Kirrel3 helps form part of a large synaptic structure called the mossy fibre synapse that is located in the hippocampus, a major region of the brain required for learning and memory. In developing mice that don't have Kirrel3, the mossy fibre synapse becomes malformed, causing the hippocampus to become overactive.

"In addition to being in the hippocampus, the gene is also expressed in other parts of the brain. It is possible that defects in those regions may also contribute to the neurodevelopmental disorders associated with Kirrel3" said the author.

Changes in the activity of synapses are thought to play an important role in the physical changes to the brain found in several neuropsychiatric disorders. Both synapses that inhibit and excite the stimulation of nerves are important to normal function and an imbalance between them can cause dysfunction. Decreased inhibition is implicated in autism spectrum disorders, whereas excess inhibition has been proposed to occur in mental retardation syndromes, such as Down's and Rett Syndromes.

http://elifesciences.org/content/4/e09395