Department of Anatomy, Brain Health Research Centre, University of Otago, Dunedin 9054, New Zealand.
Department of Clinical and Biomedical Sciences, University of Exeter Medical School, Hatherly Laboratories, Exeter EX4 4PS, United Kingdom.
Curr Neuropharmacol. 2024;22(9):1566-1575. doi: 10.2174/1570159X22666231115151403.
Cholinergic interneurons (ChIs) are important for learning and memory. They exhibit a multiphasic excitation-pause-rebound response to reward or sensory cues indicating a reward, believed to gate dopamine-dependent learning. Although ChIs receive extensive top-down inputs from the cortex and bottom-up inputs from the thalamus and midbrain, it is unclear which inputs are involved in the development of ChI multiphasic activity.
We used a single-unit recording of putative ChIs (pChIs) in response to cortical and visual stimulation to investigate how top-down and bottom-up inputs regulate the firing pattern of ChIs.
We demonstrated that cortical stimulation strongly regulates pChIs, with the maximum firing rate occurring at the peak of the inverted local field potential (iLFP), reflecting maximum cortical stimulation. Pauses in pChIs occurred during the descending phase of iLFP, indicating withdrawal of excitatory cortical input. Visual stimulation induced long pauses in pChIs, but it is unlikely that bottom- up inputs alone induce pauses in behaving animals. Also, the firing pattern of ChIs triggered by visual stimulation did not correlate with the iLFP as it did after cortical stimulation. Top-down and bottom-up inputs independently regulate the firing pattern of ChIs with similar efficacy but notably produce a well-defined pause in ChI firing.
This study provides evidence that the multiphasic ChI response may require both top-down and bottom-up inputs. The findings suggest that the firing pattern of ChIs correlated to the iLFP might be a useful tool for estimating the degree of contribution of top-down and bottom-up inputs in regulating the firing activity of ChIs.
胆碱能中间神经元 (ChIs) 对学习和记忆很重要。它们对奖励或感官线索表现出多相兴奋-暂停-反弹反应，表明门控多巴胺依赖学习。尽管 ChIs 从皮层接收广泛的自上而下的输入，并从丘脑和中脑接收自下而上的输入，但尚不清楚哪些输入参与了 ChI 多相活动的发展。
我们使用皮质和视觉刺激的单个神经元记录来研究自上而下和自下而上的输入如何调节 ChI 的发射模式。
我们证明皮质刺激强烈调节 pChIs，最大发射率出现在倒置局部场电位 (iLFP) 的峰值处，反映出最大皮质刺激。pChIs 在 iLFP 的下降阶段出现暂停，表明兴奋性皮质输入的撤回。视觉刺激诱导 pChIs 长时间暂停，但不太可能是单独的自下而上输入在行为动物中诱导暂停。此外，视觉刺激引发的 ChIs 发射模式与 iLFP 不相关，而与皮质刺激后不同。自上而下和自下而上的输入独立地以相似的功效调节 ChIs 的发射模式，但显著地产生 ChIs 发射的明确暂停。
这项研究提供了证据表明，多相 ChI 反应可能需要自上而下和自下而上的输入。研究结果表明，与 iLFP 相关的 ChIs 发射模式可能是一种有用的工具，可用于估计自上而下和自下而上的输入在调节 ChIs 发射活动中的贡献程度。
