Dynamic Changes of the Infralimbic Cortex and Its Regulation of the Prelimbic Cortex in Rats with Chronic Inflammatory Pain

The prelimbic cortex(PL)is actively engaged in pain modulation.The infralimbic cortex(IL)has been reported to regulate the PL.However,how this regulation affects pain remains unclear.In the present study,we recorded temporary hyper-activity of PL pyramidal neurons responding to nociceptive stimuli,but a temporary hypofunction of the IL by in vivo electrophysiological recording in rats with peripheral inflammation.Manipulation of the PL or IL had opposite effects on thermal hyperalgesia.Furthermore,the functional connectivity and chemogenetic regulation between the subregions indicated an inhibitory influence of the IL on the PL.Activation of the pathway from the IL to the PL alleviated thermal hyperalgesia,whereas its inhibition exacerbated chronic pain.Overall,our results suggest a new mechanism underlying the role of the medial prefrontal cortex in chronic pain:hypo-function of the IL leads to hyperactivity of the PL,which regulates thermal hyperalgesia,and thus contributes to the chronicity of pain.

Projections from Infralimbic Cortex to Paraventricular Thalamus Mediate Fear Extinction Retrieval

The paraventricular nucleus of the thalamus(PVT),which serves as a hub,receives dense projections from the medial prefrontal cortex(mPFC)and projects to the lateral division of central amygdala(CeL).The infralimbic(IL)cortex plays a crucial role in encoding and recalling fear extinction memory.Here,we found that neurons in the PVT and IL were strongly activated during fear extinction retrieval.Silencing PVT neurons inhibited extinction retrieval at recent time point(24 h after extinction),while activating them promoted extinction retrieval at remote time point(7 d after extinction),suggesting a critical role of the PVT in extinction retrieval.In the mPFC-PVT circuit,projections from IL rather than prelimbic cortex to the PVT were dominant,and disrupting the IL-PVT projection suppressed extinction retrieval.Moreover,the axons of PVT neurons preferentially projected to the CeL.Silencing the PVT-CeL circuit also suppressed extinction retrieval.Together,our findings reveal a new neural circuit for fear extinction retrieval outside the classical IL-amygdala circuit.