Acute neuroinflammation increases excitability of prefrontal parvalbumin interneurons and their functional recruitment during novel object recognition.

There is an emerging body of literature suggesting that unlike the chronic neuroinflammatory response, acute neuroinflammation is self-regulated and is beneficial for central nervous system homeostasis and cognitive integrity. However, the neurophysiological alterations upon acute neuroinflammation and their implications on cognitive function remain poorly understood. In the present study, we reliably established a mouse model of acute and self-limiting neuroinflammation by administering a single intraperitoneal injection of low-dose lipopolysaccharide, which induced reversible sickness behavior and increased pro-inflammatory cytokine expression in the medial prefrontal cortex (mPFC). During acute neuroinflammation, fast-spiking parvalbumin-expressing interneurons (PV interneurons) in the mPFC exhibited a hyperexcitable phenotype exemplified by increased input resistance, decreased rheobase current, and a higher frequency of action potentials. Furthermore, PV interneurons in the prelimbic subregion of the mPFC were excessively recruited into circuits supporting novel object recognition memory, which remained intact after acute neuroinflammation. Together, our findings suggest that alterations in PV neuronal excitability resulting from acute neuroinflammation may mediate neuronal recruitment and confer a beneficial outcome on functional integrity of NOR circuit in the mPFC.