Science Editor

The link between the brain and the immune system – once thought to be entirely separate entities, more or less linked only mechanically, through the neck vertebrae attaching the skull to the rest of the body – expanded yet again this week with a report that immune system cells contribute to brain plasticity, which is at the heart of brain function.

In their experiments, a group of scientists demonstrated that microglia – the brain's immune system cells – not only protect the brain from infection. They also play a role in shaping the synapses, or connections between brain cells, that are central to neural communication.

Senior author Ania Majewska told BioWorld Today that her laboratory at the University of Rochester focuses on what she summarized as "extracellular mechanisms of plasticity."

"Most people consider [plasticity] to be something that goes on inside neurons," she said.

But neurons do not change their stripes alone; their connections are also influenced by so-called supporting cells, including glial cells such as astrocytes – and, it now appears, microglia.

Microglia, she said, can "sidle right up to neurons" and interact with them in a variety of ways. That such interactions occur under pathological conditions, in response to neuronal injury after infection or stroke, is well-established. Indeed, disposing of neuronal debris in times of illness is the primary function of microglial cells.

But in their current paper, which is published in the November 2010 edition of PLoS Biology, Majewska and first author Marie-Eve Tremblay, along with co-author Rebecca Lowry, showed that the interactions "were modulated by experience," Tremblay told BioWorld Today.

The results demonstrated that microglia "interact with synapses under nonpathological conditions," Majewska added.

The teams suspected microglia might play a role in synaptic plasticity because microglia are well known to "monitor" neurons; that is, they send out processes to transiently contact synapses, the connections between cells that determine whether and how neurons communicate.

Synaptic plasticity, or changes in such connectivity, is the way that memories are stored in the brain.

To study what if any role microglia play in such processes, the authors first used repeated imaging to study the behavior of microglia over time.

Even in the absence of an infection, when there was no immunological tasks to be done, the microglia were anything but quiet. Instead, they continuously made contacts with synapses – most often, with small dendritic spines.

Such small spines "tend to be immature, weak synapses," Majewska explained. "They are transient; they come and go."

But if they were contacted by microglia processes, they were more likely to go than to come. Spines that came to the attention of microglia were three times as likely to disappear as other spines.

Next, the team investigated animals kept in the dark for a few days at a stretch. The brain will rapidly adapt to changing conditions by changing its wiring – a very simple form of plasticity or learning.

They found that when the lights were off, microglia sprang into action. They contacted more and larger synapses, and tended to be larger themselves, which could be a sign that they were literally eating the synapses they contacted. Return to a normal light-dark cycle reversed those changes.

Previous work had shown that microglia can get rid of the debris of damaged neurons in times of illness or injury.

But Majewska said that microglial activity changes in response to light, or a lack thereof, clearly supports the notion that these immune cells have roles in shaping brain connections in the absence of neural damage, as well.

If all they were doing is fighting disease, immune cells "shouldn't care what the animal sees," she said. But when the mice were deprived of light, microglia "changed their interaction" with neurons.

Tremblay said that in the future, targeting microglia might turn out to be an avenue for fighting many diseases, both neurodegenerative and memory disorders like Alzheimer's disease, and neurodevelopmental disorders like autism and Fragile X syndrome.

But for that, it will be necessary to first learn to specifically target microglia – a goal that is on the team's more near-term list.

"We'd really like to find ways to manipulate microglia directly," she added, which would pave the way for showing directly that manipulating this cell type affects learning and memory.