The paraventricular thalamus controls a central amygdala fear circuit

Inhibiting projections from the paraventricular nucleus of the thalamus to a specific division of the amygdala prevents fear conditioning in mice, indicating an important role for the thalamus–amygdala circuit in establishing and maintaining fear responses. Fear association memories are thought to be stored in the amygdala and are accessible throughout the lifetime of an animal. However, the circuits required for retrieval of this memory at different times are still unknown. Recent work revealed that the paraventricular nucleus of the thalamus (PVT) is strongly activated following physical and psychological stress in mice, and now two papers published in this week's issue of Nature demonstrate a role for the PVT as a critical memory/retrieval node in the thalamus during the transition from short-term to long-term storage of fear association memories. Mario Penzo et al. show that inhibiting projections from the PVT to a specific division of the amygdala prevented fear conditioning via disruption of the typical fear-induced synaptic potentiation on a specific subset of interneurons found in the amygdala following behavioural fear training. Fabricio Do-Monte et al. dissociate early from late retrieval time points and demonstrate that while the PVT is critical for late-time-point fear-memory retrieval, a separate circuit originating from the prelimbic prefrontal cortex and projecting to the amygdala is critical only for early-time-point retrieval. Appropriate responses to an imminent threat brace us for adversities. The ability to sense and predict threatening or stressful events is essential for such adaptive behaviour. In the mammalian brain, one putative stress sensor is the paraventricular nucleus of the thalamus (PVT), an area that is readily activated by both physical and psychological stressors1,2,3. However, the role of the PVT in the establishment of adaptive behavioural responses remains unclear. Here we show in mice that the PVT regulates fear processing in the lateral division of the central amygdala (CeL), a structure that orchestrates fear learning and expression4,5. Selective inactivation of CeL-projecting PVT neurons prevented fear conditioning, an effect that can be accounted for by an impairment in fear-conditioning-induced synaptic potentiation onto somatostatin-expressing (SOM+) CeL neurons, which has previously been shown to store fear memory6. Consistently, we found that PVT neurons preferentially innervate SOM+ neurons in the CeL, and stimulation of PVT afferents facilitated SOM+ neuron activity and promoted intra-CeL inhibition, two processes that are critical for fear learning and expression5,6. Notably, PVT modulation of SOM+ CeL neurons was mediated by activation of the brain-derived neurotrophic factor (BDNF) receptor tropomysin-related kinase B (TrkB). As a result, selective deletion of either Bdnf in the PVT or Trkb in SOM+ CeL neurons impaired fear conditioning, while infusion of BDNF into the CeL enhanced fear learning and elicited unconditioned fear responses. Our results demonstrate that the PVT–CeL pathway constitutes a novel circuit essential for both the establishment of fear memory and the expression of fear responses, and uncover mechanisms linking stress detection in PVT with the emergence of adaptive behaviour.