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基底外侧杏仁核抑制可减少条件性味觉厌恶中的回避行为——短暂的化学遗传学沉默使行为转向持续舔舐。

Basolateral amygdala inhibition reduces avoidance in conditioned taste aversion-Transient chemogenetic silencing shifts behavior toward sustained licking.

作者信息

Inui Tadashi, Kikuchi Emi, Suzuki Yuto, Hasegawa Momoko, Wei Zimo, Huang Helai, Yoshizawa Tomohiko, Funahashi Makoto

机构信息

Oral Physiology, Department of Oral Functional Science, Division of Oral Medical Science, Faculty of Dental Medicine and Graduate School of Dental Medicine, Hokkaido University, Japan.

Oral Physiology, Department of Oral Functional Science, Division of Oral Medical Science, Faculty of Dental Medicine and Graduate School of Dental Medicine, Hokkaido University, Japan; Orthodontics, Department of Oral Functional Science, Division of Oral Medical Science, Faculty of Dental Medicine and Graduate School of Dental Medicine, Hokkaido University, Japan.

出版信息

Behav Brain Res. 2025 Oct 18;495:115784. doi: 10.1016/j.bbr.2025.115784. Epub 2025 Aug 21.

DOI:10.1016/j.bbr.2025.115784
PMID:40848811
Abstract

The basolateral amygdala (BLA) plays a critical role in aversive learning and decision‑making, yet its specific contribution to the expression of conditioned taste aversion (CTA) remains incompletely understood. Here, we examined how transient chemogenetic inhibition of the BLA influences licking microstructure and approach-avoidance behavior toward a conditioned saccharin solution. Male C57BL/6 mice received bilateral BLA injections of AAV8‑hSyn‑hM4Di‑mCherry (experimental) or AAV8‑hSyn‑mCherry (control). CTA was induced by pairing saccharin (CS) with LiCl (US). Following CTA acquisition, animals were tested drug‑free (Test 1), after CNO or saline administration (Test 2), and drug‑free on the subsequent day (Test 3). In Test 2, CNO‑treated hM4Di‑expressing mice showed increased total licking, larger mean burst sizes, and a greater frequency of large bursts (>200 licks), accompanied by longer Entry‑Lick durations and reduced Entry‑Stop durations. Event‑based analyses confirmed fewer prolonged pauses and more sustained licking bouts in this group. These effects were absent in control groups and did not persist into Test 3, indicating a short‑lived influence on behavioral expression without erasure of the aversive memory. Together with previous manganese‑enhanced MRI evidence of BLA projections to the central amygdala, nucleus accumbens, and bed nucleus of the stria terminalis engaged during CTA expression, these results suggest that BLA activity modulates moment‑to‑moment avoidance through its downstream circuits. The findings provide new insight into the amygdala's role in regulating complex ingestive behaviors and highlight potential neural targets for modifying maladaptive avoidance.

摘要

基底外侧杏仁核(BLA)在厌恶学习和决策中起着关键作用,但其对条件性味觉厌恶(CTA)表达的具体贡献仍未完全明确。在此,我们研究了对BLA进行短暂化学遗传抑制如何影响对条件性糖精溶液的舔舐微观结构以及趋近 - 回避行为。雄性C57BL/6小鼠双侧杏仁核基底外侧注射AAV8 - hSyn - hM4Di - mCherry(实验组)或AAV8 - hSyn - mCherry(对照组)。通过将糖精(条件刺激,CS)与氯化锂(非条件刺激,US)配对来诱导CTA。在CTA习得后,对动物进行无药物测试(测试1),在注射CNO或生理盐水后进行测试(测试2),并在随后一天进行无药物测试(测试3)。在测试2中,接受CNO处理的表达hM4Di的小鼠表现出总舔舐次数增加、平均爆发大小更大以及大爆发(>200次舔舐)频率更高,同时进入 - 舔舐持续时间更长且进入 - 停止持续时间缩短。基于事件的分析证实该组中长时间停顿减少且持续舔舐发作增多。对照组未出现这些效应,且这些效应在测试3中未持续存在,表明对行为表达有短暂影响,而不会消除厌恶记忆。结合先前锰增强MRI显示在CTA表达期间BLA向中央杏仁核、伏隔核和终纹床核投射的证据,这些结果表明BLA活动通过其下游回路调节即时回避。这些发现为杏仁核在调节复杂摄食行为中的作用提供了新见解,并突出了用于改变适应不良回避的潜在神经靶点。

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