PDF(Pubmed)
Abstract：
While the functional and behavioral role of the medial habenula (MHb) is still emerging, recent data indicate an involvement of this nuclei in regulating mood, aversion, and addiction. Unique to the MHb is a large cluster of cholinergic neurons that project to the interpeduncular nucleus and densely express acetylcholine receptors (AChRs) suggesting that the activity of these cholinergic neurons may be regulated by ACh itself. Whether endogenous ACh from within the habenula regulates cholinergic neuron activity has not been demonstrated. Supporting a role for ACh in modulating MHb activity, acetylcholinesterase inhibitors increased the firing rate of MHb cholinergic neurons in mouse habenula slices, an effect blocked by AChR antagonists and mediated by ACh which was detected via expressing fluorescent ACh sensors in MHb in vivo. To test if cholinergic afferents innervate MHb cholinergic neurons, we used anterograde and retrograde viral tracing to identify cholinergic inputs. Surprisingly, tracing experiments failed to detect cholinergic inputs into the MHb, including from the septum, suggesting that MHb cholinergic neurons may release ACh within the MHb to drive cholinergic activity. To test this hypothesis, we expressed channelrhodopsin in a portion of MHb cholinergic neurons while recording from non-opsin-expressing neurons. Light pulses progressively increased activity of MHb cholinergic neurons indicating feed-forward activation driven by MHb ACh release. These data indicate MHb cholinergic neurons may utilize a unique feed-forward mechanism to synchronize and increase activity by releasing local ACh.
摘要：
虽然内囊（MHb）的功能和行为作用仍在显现，最近的数据表明这个原子核参与调节情绪，厌恶,和上瘾。MHb独有的是一大簇胆碱能神经元，它们投射到节间核并密集表达乙酰胆碱受体（AChR），这表明这些胆碱能神经元的活性可能受ACh本身的调节。尚未证明来自hub子体内的内源性ACh是否调节胆碱能神经元的活性。支持ACh在调节MHb活性中的作用，乙酰胆碱酯酶抑制剂（ACEIs）增加了MHb胆碱能神经元的放电率，通过在MHbin体内表达荧光ACh传感器检测到ACh介导的ACh效应被AChR拮抗剂阻断。为了测试胆碱能传入神经是否支配MHb胆碱能神经元，我们使用顺行和逆行病毒示踪来鉴定胆碱能输入.令人惊讶的是,示踪实验未能检测到进入MHb的胆碱能输入，包括隔膜，提示MHb胆碱能神经元可能在MHb内释放ACh以驱动胆碱能活动。为了检验这个假设，我们在部分MHb胆碱能神经元中表达了视紫红质，同时记录了非视蛋白表达神经元。光脉冲逐渐增加MHb胆碱能神经元的活性，表明由MHbACh释放驱动的前馈激活。这些数据表明MHb胆碱能神经元可以利用独特的前馈机制来通过释放局部ACh来同步和增加活性。
