The number of connections between nerve cells in the brain can be regulated by an immune system molecule¹, according to a new study from UC Davis. The research, published Feb. 27 in the journal Nature Neuroscience, reveals a potential link between immunity², infectious disease（传染病） and conditions such as schizophrenia（精神分裂症） or autism. Schizophrenia, autism and other disorders³ are associated with changes in connectivity in the brain, said Kimberley McAllister, associate professor in the Center for Neuroscience and Departments of Neurology and Neurobiology, Physiology⁴ and Behavior at UC Davis. Those changes affect the ability of the brain to process information correctly.

"Certain immune genes⁵ and immune dysregulation（调节异常） have also been associated with autism and schizophrenia, and the immune molecules⁶ that we study in brain development could be a pathway that contributes to that altered connectivity," McAllister said.

The study does not show a direct link between immune responses and autism, but rather reveals a molecular⁷ pathway through which a peripheral⁸（外围的，次要的） immune response or particular genetic⁹ profile could alter early brain development, McAllister said.

The researchers looked at a protein called Major Histocompatibility Complex type 1 (MHC type I). In both rodents¹⁰ and humans, these proteins vary between individuals, and allow the immune system to distinguish between 'self' and 'non-self.' They play a role, for example, in rejecting transplanted organs and in defending against cancer and virus infections.

In this and another recently published study, McAllister's group found that MHC type I molecules are present on young brain cells during early postnatal development. To test their function, they studied mice lacking MHC type I on the surface of neurons, as well as isolated¹¹ neurons from mice and rats with altered levels of MHC type I. They found that when the density¹² of these molecules on the surface of a brain cell goes up, the number of connections, or synapses¹⁴（突触） , it has with neighboring brain cells goes down. The reverse was also true: decreased MHC expression increased synaptic connections.

"The effect on synapse¹³ density was mediated¹⁵ through MHC type I proteins," McAllister said.

"But these immune proteins don't just regulate synapse density, they also determine the balance of excitation and inhibition on young neurons -- a property critical for information processing and plasticity in young brains."

Expression of MHCI on neurons was itself regulated by neural¹⁶ activity, the team found, and MHCI mediated the ability of neural activity to alter synaptic connections.

About 10 years ago, other researchers discovered that MHC type I is involved in elimination¹⁷ of connections during a critical period of late postnatal（出生后的） brain development.

"We have now found that there is another role for MHC type I in establishing connections during early postnatal development of the brain," McAllister said.