Neuroinflammation and Prefrontal Cortical Microcircuits: A Narrative Review of Hints from Experimental Models

Neuroinflammation is increasingly recognized as a major contributor to cognitive and neuropsychiatric dysfunction. The prefrontal cortex (PFC), a key substrate for executive functions and emotional behaviors, appears particularly vulnerable to inflammatory insults due to its high metabolic demand, prolonged developmental trajectory, and specialized microcircuit organization. In this narrative review, we focus on evidence from experimental models of neuroinflammation affecting the PFC. In particular, we approach the topic from the novel perspective of how neuroinflammation affects PFC microcircuitry, exploiting evidence from experimental models. The impact of neuroinflammatory processes on PFC microcircuit players, namely pyramidal neurons and different classes of inhibitory interneurons, will be examined and discussed. We also examine regional features that may underlie PFC susceptibility. Although available findings support the idea that neuroinflammation destabilizes PFC microcircuits, marked heterogeneity across models, timing, inflammatory burden, and readouts still limits direct comparison across studies. A more mechanistic and longitudinal understanding of these changes will be essential to clarify how inflammatory insults reshape PFC computation and contribute to cognitive dysfunction.