RT Journal Article
SR Electronic
T1 Loss of the Er81 Transcription Factor in Cholinergic Cells Alters Striatal Activity and Habit Formation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.01.14.905497
DO 10.1101/2020.01.14.905497
A1 Yadollah Ranjbar-Slamloo
A1 Noorya Yasmin Ahmed
A1 Alice Shaam Al Abed
A1 Lingxiao Gao
A1 Yovina Sontani
A1 Alexandre R’Com-H Cheo Gauthier
A1 Ehsan Arabzadeh
A1 Nathalie Dehorter
YR 2020
UL http://biorxiv.org/content/early/2020/01/15/2020.01.14.905497.abstract
AB The finely-tuned activity of cholinergic interneurons (CINs) in the striatum is key for motor control, learning, and habit formation. Yet, the molecular mechanisms that determine their unique functional properties remain poorly explored. Using a combination of genetic and biochemical assays, in vitro and in vivo physiological characterisation, we report that selective ablation of the Er81 transcription factor leads to prominent changes in CIN molecular, morphological and electrophysiological features. In particular, the lack of Er81 amplifies intrinsic delayed-rectifier and hyperpolarization-activated currents, which subsequently alters the tonic and phasic activity of CINs. We further demonstrate that these alterations enhance their pause and time-locked responses to sensorimotor inputs in awake mice. Finally, this study reveals an Er81-dependent developmental mechanism in CINs essential for habit formation in adult mice.Highlights - The Er81 transcription factor is expressed in striatal cholinergic interneurons (CINs)- Conditional deletion of Er81 alters key molecular, morphological and electrophysiological properties of CINs in adult mice- Deletion of Er81 reduces the intrinsic excitability of CINs by upregulating delayed rectifier and hyperpolarization-activated currents- Deletion of Er81 alters in vivo striatal activity and habit formation