Cholinergic neuronal lesions in the medial septum and vertical limb of the diagonal bands of Broca induce contextual fear memory generalization and impair acquisition of fear extinction.
Cholinergic neuronal lesions in the medial septum and vertical limb of the diagonal bands of Broca induce contextual fear memory generalization and impair acquisition of fear extinction.
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DOI：
10.1002/hipo.22553
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发表时间：
2016-06
期刊：
影响因子：
3.5
通讯作者：
Keller SM
中科院分区：
文献类型：
--
作者：
Knox D;Keller SM
先前的研究表明，腹侧内侧前额叶皮层（vmPFC）和海马体（Hipp）对消失记忆至关重要。基底前脑（BF）胆碱能输入到vmPFC和Hipp对这些底物的神经功能至关重要，这表明BF胆碱能神经元可能对消退记忆至关重要。为了验证这一假设，我们将胆碱能损伤应用于BF的不同区域，观察这些损伤对消失记忆的影响。完全性BF胆碱能损伤诱发情境恐惧记忆泛化，且这种泛化恐惧具有抵抗性。完全BF胆碱能病变的动物不能获得提示性恐惧消退。中隔和Broca垂直对角带的限制性胆碱能病变（MS/vDBB）模拟BF胆碱能病变对情境恐惧记忆泛化和恐惧消退习得的影响。基底核水平对角线带胆碱能损伤（hDBB/NBM）引起了小范围的泛化情境恐惧记忆消退缺陷，但没有提示恐惧消退缺陷。本研究结果表明，MS/vDBB胆碱能神经元在泛化情境恐惧记忆的抑制和消退过程中起关键作用，并可能通过这一过程对线索恐惧消退的习得起关键作用。需要进一步研究MS/vDBB胆碱能神经元促进这些情绪记忆过程的神经回路和机制。
Previous research has shown that the ventral medial prefrontal cortex (vmPFC) and hippocampus (Hipp) are critical for extinction memory. Basal forebrain (BF) cholinergic input to the vmPFC and Hipp is critical for neural function in these substrates, which suggests BF cholinergic neurons may be critical for extinction memory. In order to test this hypothesis, we applied cholinergic lesions to different regions of the BF and observed the effects these lesions had on extinction memory. Complete BF cholinergic lesions induced contextual fear memory generalization, and this generalized fear was resistant to extinction. Animals with complete BF cholinergic lesions could not acquire cued fear extinction. Restricted cholinergic lesions in the medial septum and vertical diagonal bands of Broca (MS/vDBB) mimicked the effects that BF cholinergic lesions had on contextual fear memory generalization and acquisition of fear extinction. Cholinergic lesions in the horizontal diagonal band of Broca and nucleus basalis (hDBB/NBM) induced a small deficit in extinction of generalized contextual fear memory with no accompanying deficits in cued fear extinction. The results of this study reveal that MS/vDBB cholinergic neurons are critical for inhibition and extinction of generalized contextual fear memory, and via this process, may be critical for acquisition of cued fear extinction. Further studies delineating neural circuits and mechanisms through which MS/vDBB cholinergic neurons facilitate these emotional memory processes are needed.