Abstract：
At the heart of the prefrontal network is the mediodorsal (MD) thalamus. Despite the importance of MD in a broad range of behaviors and neuropsychiatric disorders, little is known about the physiology of neurons in MD. We injected the retrograde tracer cholera toxin subunit B (CTB) into the medial prefrontal cortex (mPFC) of adult wild-type mice. We prepared acute brain slices and used current clamp electrophysiology to measure and compare the intrinsic properties of the neurons in MD that project to mPFC (MD→mPFC neurons). We show that MD→mPFC neurons are located predominantly in the medial (MD-M) and lateral (MD-L) subnuclei of MD. MD-L→mPFC neurons had shorter membrane time constants and lower membrane resistance than MD-M→mPFC neurons. Relatively increased hyperpolarization-activated cyclic nucleotide-gated (HCN) channel activity in MD-L neurons accounted for the difference in membrane resistance. MD-L neurons had a higher rheobase that resulted in less readily generated action potentials compared with MD-M→mPFC neurons. In both cell types, HCN channels supported generation of burst spiking. Increased HCN channel activity in MD-L neurons results in larger after-hyperpolarization potentials compared with MD-M neurons. These data demonstrate that the two populations of MD→mPFC neurons have divergent physiologies and support a differential role in thalamocortical information processing and potentially behavior.NEW & NOTEWORTHY To realize the potential of circuit-based therapies for psychiatric disorders that localize to the prefrontal network, we need to understand the properties of the populations of neurons that make up this network. The mediodorsal (MD) thalamus has garnered attention for its roles in executive functioning and social/emotional behaviors mediated, at least in part, by its projections to the medial prefrontal cortex (mPFC). Here, we identify and compare the physiology of the projection neurons in the two MD subnuclei that provide ascending inputs to mPFC in mice. Differences in intrinsic excitability between the two populations of neurons suggest that neuromodulation strategies targeting the prefrontal thalamocortical network will have differential effects on these two streams of thalamic input to mPFC.
摘要：
前额叶网络的核心是中背丘脑（MD）。尽管MD在广泛的行为和神经精神疾病中的重要性，对MD中神经元的生理学知之甚少。我们将逆行示踪霍乱毒素B亚基（CTB）注射到成年野生型小鼠的内侧前额叶皮质（mPFC）中。我们准备了急性脑切片，并使用电流钳电生理学来测量和比较投射到mPFC（MD→mPFC神经元）的MD神经元的固有特性。我们发现MD→mPFC神经元主要位于MD的内侧（MD-M）和外侧（MD-L）亚核。MD-L→mPFC神经元比MD-M→mPFC神经元具有更短的膜时间常数和更低的膜电阻。MD-L神经元中超极化激活的环核苷酸门控（HCN）通道活性相对增加是膜电阻的差异。与MD-M→mPFC神经元相比，由于较高的流变酶，MD-L神经元不易产生动作电位。在这两种细胞类型中，HCN通道支持突发尖峰的生成。与MD-M神经元相比，MD-L神经元中HCN通道活性的增加会导致更大的超极化后电位。这些数据,证明MD→mPFC神经元的两个群体具有不同的生理学，提示在丘脑皮层信息处理和潜在行为中的不同作用。
