Neuroimmune Activation Drives Multiple Brain States

Neuroimmune signaling is increasingly identified as a critical component of neuronal processes underlying memory, emotion and cognition. The interactions of microglia and astrocytes with neurons and synapses, and the individual cytokines and immune signaling molecules that mediate these interactions are a current focus of much research. Here, we discuss neuroimmune activation as a mechanism triggering different states that modulate cognitive and affective processes to allow for appropriate behavior during and after illness or injury. We propose that these states lie on a continuum from a naïve homeostatic baseline state in the absence of stimulation, to acute neuroimmune activity and chronic activation. Importantly, consequences of illness or injury including cognitive deficits and mood impairments can persist long after resolution of immune signaling. This suggests that neuroimmune activation also results in an enduring shift in the homeostatic baseline state with long lasting consequences for neural function and behavior. Such different states can be identified in a multidimensional way, using patterns of cytokine and glial activation, behavioral and cognitive changes, and epigenetic signatures. Identifying distinct neuroimmune states and their consequences for neural function will provide a framework for predicting vulnerability to disorders of memory, cognition and emotion both during and long after recovery from illness.