Chemokines and the hippocampus: a new perspective on hippocampal plasticity and vulnerability.

The hippocampus is critical for several aspects of learning and memory and is unique among other cortical regions in structure, function and the potential for plasticity. This remarkable region recapitulates development throughout the lifespan with enduring neurogenesis and well-characterized plasticity. The structure and traits of the hippocampus that distinguish it from other brain regions, however, may be the same reasons that this important brain region is particularly vulnerable to insult and injury. The immune system within the brain responds to insult and injury, and the hippocampus and the immune system are extensively interconnected. Immune signaling molecules, cytokines and chemokines (chemotactic cytokines), are well known for their functions during insult or injury. They are also increasingly implicated in normal hippocampal neurogenesis (e.g., CXCR4 on newborn neurons), cellular plasticity (e.g., interleukin-6 in LTP maintenance), and learning and memory (e.g., interleukin-1β in fear conditioning). We provide evidence from the small but growing literature that neuroimmune interactions and immune signaling molecules, especially chemokines, may be a primary underlying mechanism for the coexistence of plasticity and vulnerability within the hippocampus. We also highlight the evidence that the hippocampus exhibits a remarkable resilience in response to diverse environmental events (e.g., enrichment, exercise), which all may converge onto common neuroimmune mechanisms.