Projections from Infralimbic Cortex to Paraventricular Thalamus Mediate Fear Extinction Retrieval

Neurosci Bull. 2021 Feb;37(2):229-241. doi: 10.1007/s12264-020-00603-6. Epub 2020 Nov 12.

Abstract

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.

Keywords: Amygdala; Fear extinction retrieval; Infralimbic cortex; Medial prefrontal cortex; Neural circuit; Paraventricular thalamus; Post-traumatic stress disorder.

MeSH terms

  • Central Amygdaloid Nucleus*
  • Extinction, Psychological
  • Fear*
  • Prefrontal Cortex
  • Thalamus