TY - JOUR
T1 - Central Cholinergic Neurons Are Rapidly Recruited by Reinforcement Feedback
AU - Hangya, Balázs
AU - Ranade, Sachin P.
AU - Lorenc, Maja
AU - Kepecs, Adam
N1 - Funding Information:
This work was supported by grants from the John Merck and McKnight Foundations and the National Institute of Neurological Disorders and Stroke (R01NS075531) (to A.K.). B.H. received support from the Swartz Foundation and Marie Curie International Outgoing Fellowship within the EU Seventh Framework Programme for Research and Technological Development. The authors are grateful to Barry Burbach and Rob Eifert for invaluable technical assistance; Goncalo Lopez for help with Bonsai; Sanchari Ghosh for assisting in recording cholinergic neurons outside the behavioral task; and Hyun-Jae Pi, Duda Kvitsiani, Joshua I. Sanders, Michael Long, Stephen Shea, and Jessica Tollkuhn for helpful comments and discussions.
Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015/8/27
Y1 - 2015/8/27
N2 - Summary Basal forebrain cholinergic neurons constitute a major neuromodulatory system implicated in normal cognition and neurodegenerative dementias. Cholinergic projections densely innervate neocortex, releasing acetylcholine to regulate arousal, attention, and learning. However, their precise behavioral function is poorly understood because identified cholinergic neurons have never been recorded during behavior. To determine which aspects of cognition their activity might support, we recorded cholinergic neurons using optogenetic identification in mice performing an auditory detection task requiring sustained attention. We found that a non-cholinergic basal forebrain population - but not cholinergic neurons - were correlated with trial-to-trial measures of attention. Surprisingly, cholinergic neurons responded to reward and punishment with unusual speed and precision (18 ± 3 ms). Cholinergic responses were scaled by the unexpectedness of reinforcement and were highly similar across neurons and two nuclei innervating distinct cortical areas. These results reveal that the cholinergic system broadcasts a rapid and precisely timed reinforcement signal, supporting fast cortical activation and plasticity.
AB - Summary Basal forebrain cholinergic neurons constitute a major neuromodulatory system implicated in normal cognition and neurodegenerative dementias. Cholinergic projections densely innervate neocortex, releasing acetylcholine to regulate arousal, attention, and learning. However, their precise behavioral function is poorly understood because identified cholinergic neurons have never been recorded during behavior. To determine which aspects of cognition their activity might support, we recorded cholinergic neurons using optogenetic identification in mice performing an auditory detection task requiring sustained attention. We found that a non-cholinergic basal forebrain population - but not cholinergic neurons - were correlated with trial-to-trial measures of attention. Surprisingly, cholinergic neurons responded to reward and punishment with unusual speed and precision (18 ± 3 ms). Cholinergic responses were scaled by the unexpectedness of reinforcement and were highly similar across neurons and two nuclei innervating distinct cortical areas. These results reveal that the cholinergic system broadcasts a rapid and precisely timed reinforcement signal, supporting fast cortical activation and plasticity.
UR - http://www.scopus.com/inward/record.url?scp=84940382102&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2015.07.057
DO - 10.1016/j.cell.2015.07.057
M3 - Article
C2 - 26317475
AN - SCOPUS:84940382102
SN - 0092-8674
VL - 162
SP - 1155
EP - 1168
JO - Cell
JF - Cell
IS - 5
ER -