Anxiety disorders such as post-traumatic stress are characterized by an impaired ability to learn that cues previously associated with danger no longer represent a threat. However, the mechanisms underlying fear extinction remain unclear. Here we show in rats that extinction is associated with increased levels of synaptic inhibition in fear output neurons of the central amygdala (CEA). This increased inhibition results from a potentiation of fear input synapses to GABAergic intercalated amygdala neurons that project to CEA. Enhancement of inputs to intercalated cells required prefrontal activity during extinction training and involved a higher transmitter release probability coupled to an altered expression profile of ionotropic glutamate receptors. Overall, our results suggest that intercalated cells constitute a promising target for pharmacological treatments aiming to facilitate the treatment of anxiety disorders.
The lateral nucleus (LA) is the input station of the amygdala for information about conditioned stimuli (CS), whereas the medial sector of the central nucleus (CeM) is the output region that contributes most amygdala projections to brainstem fear effectors. However, there are no direct links between LA and CeM. As the main target of LA and with its strong projection to CeM, the basomedial amygdala (BM) constitutes a good candidate to bridge this gap. Consistent with this notion, it was reported that combined post-training lesions of the basal nuclei (BM plus basolateral -BL- nucleus) abolish conditioned fear responses whereas selective BL inactivation does not. Thus, we examined the relative contribution of BM and BL to conditioned fear using unit recordings and inactivation with muscimol micro-infusions in rats. Around 30% of BM and BL neurons acquired robust responses to auditory CSs predicting footshocks. While most BL cells stopped firing at CS offset, BM responses typically outlasted the CS by ≥40s, paralleling the persistence of conditioned fear after the CS. This observation suggests that BM neurons are not passive relays of rapidly adapting LA inputs about the CS. Surprisingly, independent inactivation of either BM or BL with muscimol did not cause a reduction of conditioned freezing even though an extinction recall deficit was seen the next day. In contrast, combined BL–BM inactivation did. Overall, there results support the notion that the basal nuclei are involved in conditioned fear expression and extinction but that there is functional redundancy between them.
Paternal behavior is not innate but arises through social experience. After mating and becoming fathers, male mice change their behavior toward pups from infanticide to paternal care. However, the precise brain areas and circuit mechanisms connecting these social behaviors are largely unknown. Here we demonstrated that the c-Fos expression pattern in the four nuclei of the preoptic-bed nuclei of stria terminalis (BST) region could robustly discriminate five kinds of previous social behavior of male mice (parenting, infanticide, mating, inter-male aggression, solitary control). Specifically, neuronal activation in the central part of the medial preoptic area (cMPOA) and rhomboid nucleus of the BST (BSTrh) retroactively detected paternal and infanticidal motivation with more than 95% accuracy. Moreover, cMPOA lesions switched behavior in fathers from paternal to infanticidal, while BSTrh lesions inhibited infanticide in virgin males. The projections from cMPOA to BSTrh were largely GABAergic. Optogenetic or pharmacogenetic activation of cMPOA attenuated infanticide in virgin males. Taken together, this study identifies the preoptic-BST nuclei underlying social motivations in male mice and reveals unexpected complexity in the circuit connecting these nuclei.
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