Synaptic plasticity in two cell types of central amygdala for regulation of emotion and pain

Abstract

The amygdala is a critical brain site for regulation of emotion-associated behaviors such as pain and anxiety. Recent studies suggest that differential cell types and synaptic circuits within the amygdala complex mediate interacting and opposing effects on emotion and pain. However, the underlying cellular and circuit mechanisms are poorly understood at present. Here we used optogenetics combined with electrophysiological analysis of synaptic inputs to investigate pain-induced synaptic plasticity within the amygdala circuits in rats. We found that 50% of the cell population in the lateral division of the central nucleus of the amygdala (CeAl) received glutamate inputs from both basolateral amygdala (BLA) and from the parabrachial nucleus (PBN), and 39% of the remaining CeAl cells received glutamate inputs only from PBN. Inflammatory pain lasting 3 days, which induced anxiety, produced sensitization in synaptic activities of the BLA–CeAl–medial division of CeA (CeAm) pathway primarily through a postsynaptic mechanism. Moreover, in CeAl cells receiving only PBN inputs, pain significantly augmented the synaptic strength of the PBN inputs. In contrast, in CeAl cells receiving both BLA and PBN inputs, pain selectively increased the synaptic strength of BLA inputs, but not the PBN inputs. Electrophysiological analysis of synaptic currents showed that the increased synaptic strength in both cases involved a postsynaptic mechanism. These findings reveal two main populations of CeAl cells that have differential profiles of synaptic inputs and show distinct plasticity in their inputs in response to anxiety-associated pain, suggesting that the specific input plasticity in the two populations of CeAl cells may encode a different role in amygdala regulation of pain and emotion.

Tumor-infiltrating nerves functionally alter brain circuits and modulate behavior in a mouse model of head-and-neck cancer

“…Significantly, patients suffering from HNSCC often experience depressive disorders, which are poorly managed clinically [84][85][86] . Here, we found that nociceptor neurons infiltrating HNSCC connect to a preexisting brain-projecting circuit 87,88 that includes the trigeminal ganglia, the spinal nucleus of the trigeminal (SpVc), as well as the parabrachial nucleus (PBN), and central amygdala (CeA) [89][90][91][92] .…”

The projection from dorsal medial prefrontal cortex to basolateral amygdala promotes behaviors of negative emotion in rats

“…The open field test was conducted in an illuminated chamber (72 × 72 × 50 cm) divided by a central zone and an outer zone as we described before ( Cai et al, 2018 ; Ge et al, 2022 ). A rat was connected to the light source and was placed in the center of the chamber.…”

Brain nuclei and neural circuits in neuropathic pain and brain modulation mechanisms of acupuncture: a review on animal-based experimental research

“…Opposite changes may lead to NP and memory deficits, respectively ( Liu et al, 2017 ). The amygdala, ACC, and other key brain nuclei for sensing emotion-related behaviors such as pain and anxiety are also highly plastic ( Zhuo, 2020 ; Ge et al, 2022 ). Thus, modulating structural or functional plasticity in brain synapses can inhibit central sensitization and thus reduce NP.…”