ASIC1a regulates insular long-term depression and is required for the extinction of conditioned taste aversion

Li, Wei Guang; Liu, Ming Gang; Deng, Shining; Liu, Yan Mei; Shang, Lin; Ding, Jing; Hsu, Tsan Ting; Jiang, Qin; Liu, Ying; Li, Fēi; Zhu, Michael X.

doi:10.1038/ncomms13770

Cited by 51 publications

(59 citation statements)

References 70 publications

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“…12 Thus, ASIC1A is implicated in both synaptic potentiation and depression in multiple brain areas, which might help explain the diverse effects of ASIC1A disruption observed in these studies. 12 Thus, ASIC1A is implicated in both synaptic potentiation and depression in multiple brain areas, which might help explain the diverse effects of ASIC1A disruption observed in these studies.…”

Section: Conditioned Responses In the Absence Of Reinforcementmentioning

confidence: 88%

“…Consistent with the above observations, effects of ASIC1A on Pavlovian conditioning to aversive stimuli have been described. 12 Together, these findings suggest an important role for ASIC1A in Pavlovian conditioning to aversive stimuli. 4,6,[17][18][19][20] These deficits were reproduced with amygdalaspecific ASIC1A disruption, 17 and a deficit in contextual fear memory was rescued by expressing ASIC1A in the amygdala.…”

mentioning

confidence: 83%

“…In contrast, Asic1a −/− mice acquired conditioned taste aversion normally, although extinction was impaired. 12 Together, these findings suggest an important role for ASIC1A in Pavlovian conditioning to aversive stimuli.…”

mentioning

confidence: 83%

“…5,7,[13][14][15] Effects of ASIC1A disruption on dendritic spine density and glutamate receptor composition and function have been reported, 7,13,15,16 as well as effects on long-term potentiation 5,7,17 and long-term depression. 12 Thus, through its location and function, ASIC1A may be well positioned to influence Pavlovian conditioning.…”

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confidence: 99%

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A novel role for acid‐sensing ion channels in Pavlovian reward conditioning

Ghobbeh

Taugher

Alam

et al. 2018

Genes Brain and Behavior

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Pavlovian fear conditioning has been shown to depend on acid‐sensing ion channel‐1A (ASIC1A); however, it is unknown whether conditioning to rewarding stimuli also depends on ASIC1A. Here, we tested the hypothesis that ASIC1A contributes to Pavlovian conditioning to a non‐drug reward. We found effects of ASIC1A disruption depended on the relationship between the conditional stimulus (CS) and the unconditional stimulus (US), which was varied between five experiments. In experiment 1, when the CS preceded the US signaling an upcoming reward, Asic1a−/− mice exhibited a deficit in conditioning compared to Asic1a+/+ mice. Alternatively, in experiment 2, when the CS coinitiated with the US and signaled immediate reward availability, the Asic1a−/− mice exhibited an increase in conditioned responses compared to Asic1a+/+ mice, which contrasted with the deficits in the first experiment. Furthermore, in experiments 3 and 4, when the CS partially overlapped in time with the US, or the CS was shortened and coinitiated with the US, the Asic1a−/− mice did not differ from control mice. The contrasting outcomes were likely because of differences in conditioning because in experiment 5 neither the Asic1a−/− nor Asic1a+/+ mice acquired conditioned responses when the CS and US were explicitly unpaired. Taken together, these results suggest that the effects of ASIC1A disruption on reward conditioning depend on the temporal relationship between the CS and US. Furthermore, these results suggest that ASIC1A plays a critical, yet nuanced role in Pavlovian conditioning. More research will be needed to deconstruct the roles of ASIC1A in these fundamental forms of learning and memory.

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Section: Conditioned Responses In the Absence Of Reinforcementmentioning

confidence: 88%

mentioning

confidence: 83%

mentioning

confidence: 83%

mentioning

confidence: 99%

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A novel role for acid‐sensing ion channels in Pavlovian reward conditioning

Ghobbeh

Taugher

Alam

et al. 2018

Genes Brain and Behavior

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“…In contrast to the established role for ASIC1a in LTP, which promotes associative learning and memory in several brain areas, ASIC1a is a critical modulator of LTD in the insular cortex and this function is important for the extinction of the acquired taste aversion memory. Furthermore, since the diminished LTD in ASIC1a null mice was restored by re‐introduction of WT, but not the pore‐dead mutant of ASIC1a in insular neurons, the ionic conductance of ASIC1a is crucial for its role in insular synaptic depression (Li et al, ).…”

Section: Asic Channels and Synaptic Plasticitymentioning

confidence: 99%

Synaptic signals mediated by protons and acid‐sensing ion channels

Uchitel

Inchauspe

Weissmann

2019

Synapse

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Extracellular pH changes may constitute significant signals for neuronal communication. During synaptic transmission, changes in pH in the synaptic cleft take place. Its role in the regulation of presynaptic Ca2+ currents through multivesicular release in ribbon‐type synapses is a proven phenomenon. In recent years, protons have been recognized as neurotransmitters that participate in neuronal communication in synapses of several regions of the CNS such as amygdala, nucleus accumbens, and brainstem. Protons are released by nerve stimulation and activate postsynaptic acid‐sensing ion channels (ASICs). Several types of ASIC channels are expressed in the peripheral and central nervous system. The influx of Ca2+ through some subtypes of ASICs, as a result of synaptic transmission, agrees with the participation of ASICs in synaptic plasticity. Pharmacological and genetical inhibition of ASIC1a results in alterations in learning, memory, and phenomena like fear and cocaine‐seeking behavior. The recognition of endogenous molecules, such as arachidonic acid, cytokines, histamine, spermine, lactate, and neuropeptides, capable of inhibiting or potentiating ASICs suggests the existence of mechanisms of synaptic modulation that have not yet been fully identified and that could be tuned by new emerging pharmacological compounds with potential therapeutic benefits.

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Dorsolateral Striatal proBDNF Improves Reversal Learning by Enhancing Coordination of Neural Activity in Rats

Sun

Che

et al. 2020

Mol Neurobiol

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ASIC1a regulates insular long-term depression and is required for the extinction of conditioned taste aversion

Cited by 51 publications

References 70 publications

A novel role for acid‐sensing ion channels in Pavlovian reward conditioning

A novel role for acid‐sensing ion channels in Pavlovian reward conditioning

Synaptic signals mediated by protons and acid‐sensing ion channels

Dorsolateral Striatal proBDNF Improves Reversal Learning by Enhancing Coordination of Neural Activity in Rats

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