Persistent exposure to stressful events can produce serious and lasting disturbances in cognitive function and mood state. 

Research directed towards understanding why these changes occur has discovered that one of the central mechanisms involved is the ability of stress to reduce the number of synaptic contacts between neurons. While the neurobiological processes involved in precipitating this reduction have remained elusive, several studies have suggested that microglia may play a central role. Firstly, it has recently been shown that microglia are extremely active in both modifying and removing synapses within the healthy brain. Secondly, the CIA’s research team has discovered compelling evidence that psychological stress profoundly alters microglial activation, particularly within the prefrontal cortex, and that pharmacological inactivation of microglia attenuates the magnitude of stress-induced cognitive impairments. Putting these two significant findings together, we propose that stress-induced microglial alterations may play a central role in stress-induced reductions in synaptic density. Accordingly, the principal objective of the current proposal is to understand, at a neuroanatomical level, how exposure to stress alters the interaction between microglia and synapses. The studies to be undertaken in this proposal will provide fundamental knowledge on microglial driven neuronal plasticity, a novel and emerging area of research within psychiatric neuroscience and neuroscience more broadly.


Dr Frederick Rohan Walker 

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