TY - JOUR
T1 - Thalamic projections sustain prefrontal activity during working memory maintenance
AU - Bolkan, Scott S.
AU - Stujenske, Joseph M.
AU - Parnaudeau, Sebastien
AU - Spellman, Timothy J.
AU - Rauffenbart, Caroline
AU - Abbas, Atheir I.
AU - Harris, Alexander Z.
AU - Gordon, Joshua A.
AU - Kellendonk, Christoph
N1 - Funding Information:
This work was supported by grants from the NIMH (R01 MH096274 to J.A.G., F31 MH102041 to S.S.B. and F30 MH107204 to J.M.S.); by the Hope for Depression Research Foundation (to J.A.G.); and by the Irma Hirschl Trust (to C.K.).
Publisher Copyright:
© 2017 Nature America, Inc., part of Springer Nature. All rights reserved.
PY - 2017/6/27
Y1 - 2017/6/27
N2 - 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.
AB - 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.
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U2 - 10.1038/nn.4568
DO - 10.1038/nn.4568
M3 - Article
C2 - 28481349
AN - SCOPUS:85020395534
SN - 1097-6256
VL - 20
SP - 987
EP - 996
JO - Nature Neuroscience
JF - Nature Neuroscience
IS - 7
ER -