Increase in proton concentration [H⁺] or decrease in local and global extracellular pH occurs in both physiological and pathological conditions. Acid-sensing ion channels (ASICs), belonging to the ENaC/Deg superfamily, play an important role in signal transduction as proton sensor. ASICs and in particular ASIC-1a (one of the six ASICs subunits) which is permeable to Ca²⁺, are involved in many physiological processes (including synaptic plasticity) and neurodegenerative diseases. Activity-dependent long-term potentiation (LTP) is a major type of long-lasting synaptic plasticity in the CNS, associated with learning, memory, development, fear and persistent pain. Neurons in the anterior cingulate cortex (ACC) play critical roles in pain perception and chronic pain and express ASIC-1a channels. During synaptic transmission, acidification of the synaptic cleft presumably due to the co-release of neurotransmitter and H⁺ from synaptic vesicles activates postsynaptic ASIC-1a channels in ACC of mice. This generates ASIC1a synaptic currents that add to the glutamatergic excitatory postsynaptic currents (EPSCs). Here we report that modulators like histamine and corticosterone, acting through ASIC-1a regulate synaptic plasticity, reducing the threshold for LTP induction of glutamatergic EPSCs. Our findings suggest a new role for ASIC-1a mediating the neuromodulator action of histamine and corticosterone regulating specific forms of synaptic plasticity in the mouse ACC.

在生理和病理条件下，质子浓度[H ⁺ ]的增加或局部和整体细胞外pH的降低都会发生。属于ENaC / Deg超家族的酸敏感离子通道（ASIC）作为质子传感器在信号传导中起着重要作用。可以渗透Ca ^2+的ASIC，尤其是ASIC-1a（六个ASIC子单元之一）参与许多生理过程（包括突触可塑性）和神经退行性疾病。依赖活动的长期增强（LTP）是中枢神经系统中持久的突触可塑性的主要类型，与学习，记忆，发育，恐惧和持续性疼痛相关。前扣带回皮层（ACC）中的神经元在疼痛感知和慢性疼痛中起关键作用，并表达ASIC-1a通道。在突触传递过程中，可能是由于神经递质和H ⁺的共同释放导致突触裂的酸化来自突触小泡的细胞激活小鼠ACC中的突触后ASIC-1a通道。这会产生ASIC1a突触电流，这些电流会添加到谷氨酸能兴奋性突触后电流（EPSC）中。在这里我们报告说，通过ASIC-1a作用的组胺和皮质酮等调节剂可调节突触可塑性，降低LTP诱导的谷氨酸能EPSC的阈值。我们的发现表明ASIC-1a介导组胺和皮质酮的神经调节剂调节小鼠ACC突触可塑性的特定形式的新作用。