The spines of both semaphorin-lacking and neuropilin-lacking mice were dramatically enlarged, compared to those of the smaller, spherical-looking spines in the wild-type mice. In wild types, Tran generally noted a single site of connection per spine. In the mutants, the site of connection between two neurons was often split.

Next, the team recorded the electrical output of mutant and wild-type neurons and found that the mutants, with more spines and larger spines, also had about a 2.5-times increase in the frequency of electrical activity, suggesting that this abnormal synaptic transmission is due to an increase in the number of synapses.

What causes synapses to form or not form in appropriate or inappropriate places is an extremely important and poorly understood process in the development of the nervous system, Kolodkin says, explaining that the neurons his team studies can have up to 10,000 synaptic connections with other neurons. If connections between neurons are not being formed how and where they're supposed to, then miscommunication occurs and circuits malfunction; as a result, any number of diseases or disorders might develop.

"Seizures can be interpreted as an uncontrolled rapid-firing of certain neural circuits," Kolodkin asserts. "Clearly there's a deficit in these animals that has a human corollary with respect to epilepsy. It's also thought that schizophrenia and autism spectrum disorders have developmental origins of one sort or another. There likely are aspects to the formation of synapses - if they're not in the correct location and in the correct number - that lead to certain types of defects. The spine deficits in these mice that are lacking semaphorin or its receptor appear very similar to those that are found in Fragile X, for instance."

Source: Johns Hopkins Medical Institutions