Thalamic projections sustain prefrontal activity during working memory maintenance

• DOI: 10.1038/nn.4568
• Publication Date: 2017-05-08T15:04:30Z
• Authors: Scott S Bolkan; Joseph M Stujenske; Sebastien Parnaudeau; Timothy J Spellman; Caroline Rauffenbart; Atheir I Abbas; Alexander Z Harris; Joshua A Gordon; Christoph Kellendonk
• Keywords: Male; Neurons; 0301 basic medicine; Time Factors; [SDV]Life Sciences [q-bio]; Action Potentials; Prefrontal Cortex; Choice Behavior; Hippocampus; Article; 12. Responsible consumption; Mice; 03 medical and health sciences; Memory, Short-Term; Thalamus; Neural Pathways; Animals; Humans; [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]; [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]; Maze Learning; Spatial Memory

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.