Bolkan Scott S, Stujenske Joseph M, Parnaudeau Sebastien, Spellman Timothy J, Rauffenbart Caroline, Abbas Atheir I, Harris Alexander Z, Gordon Joshua A, Kellendonk Christoph
Columbia University, College of Physicians and Surgeons, New York, New York, USA.
Institut de Biologie Paris Seine, UM119, Neuroscience Paris Seine, CNRS UMR8246, INSERM U1130, Paris, France.
Nat Neurosci. 2017 Jul;20(7):987-996. doi: 10.1038/nn.4568. Epub 2017 May 3.
The mediodorsal thalamus (MD) shares reciprocal connectivity with the prefrontal cortex (PFC), and decreased MD-PFC connectivity is observed in schizophrenia patients. Patients also display cognitive deficits including impairments in working memory, but a mechanistic link between thalamo-prefrontal circuit function and working memory is missing. Using pathway-specific inhibition, we found directional interactions between mouse MD and medial PFC (mPFC), with MD-to-mPFC supporting working memory maintenance and mPFC-to-MD supporting subsequent choice. We further identify mPFC neurons that display elevated spiking during the delay, a feature that was absent on error trials and required MD inputs for sustained maintenance. Strikingly, delay-tuned neurons had minimal overlap with spatially tuned neurons, and each mPFC population exhibited mutually exclusive dependence on MD and hippocampal inputs. These findings indicate a role for MD in sustaining prefrontal activity during working memory maintenance. Consistent with this idea, we found that enhancing MD excitability was sufficient to enhance task performance.
丘脑背内侧核（MD）与前额叶皮质（PFC）存在相互连接，且在精神分裂症患者中观察到MD - PFC连接性降低。患者还表现出认知缺陷，包括工作记忆受损，但丘脑 - 前额叶回路功能与工作记忆之间的机制联系尚不清楚。通过通路特异性抑制，我们发现小鼠MD与内侧前额叶皮质（mPFC）之间存在方向性相互作用，MD到mPFC支持工作记忆维持，mPFC到MD支持后续选择。我们进一步鉴定出在延迟期间放电增加的mPFC神经元，这一特征在错误试验中不存在，且持续维持需要MD输入。引人注目的是，延迟调谐神经元与空间调谐神经元的重叠极少，并且每个mPFC群体对MD和海马体输入表现出相互排斥的依赖性。这些发现表明MD在工作记忆维持期间维持前额叶活动中发挥作用。与此观点一致，我们发现增强MD兴奋性足以提高任务表现。
