TY - JOUR
T1 - Serotonergic regulation of bipolar cell survival in the developing cerebral cortex
AU - Wong, Fong Kuan
AU - Selten, Martijn
AU - Rosés-Novella, Claudia
AU - Sreenivasan, Varun
AU - Pallas-Bazarra, Noemí
AU - Serafeimidou-Pouliou, Eleni
AU - Hanusz-Godoy, Alicia
AU - Oozeer, Fazal
AU - Edwards, Robert
AU - Marín, Oscar
N1 - Funding Information:
We thank I. Andrews for excellent technical assistance, K. Nave (Max Planck Institute for Experimental Medicine, Germany) for NexCre/+ mice, J. Burrone and B. Rico for critical reading of the manuscript, and members of the Marín and Rico laboratories for stimulating discussions and ideas. This work was supported by grants from the European Research Council (ERC-2017-AdG 787355) and the European Union's Horizon 2020 Research and Innovation Programme AIMS-2-TRIALS (777394) to O.M. F.K.W. and O.M. conceived the study. F.K.W. performed most experiments described in this manuscript. F.K.W. and C.R.-N. performed initial experiments establishing the programmed cell death of Htr3a+ interneurons. M.S. performed electrophysiological experiments. V.S. E.S.-P. and A.H.-G. contributed to data collection. F.O. prepared AAVs. N.P.-B. validated the shRNA constructs and viruses. R.E. contributed Vglut1 and Vglut2 mice. F.K.W. and O.M. wrote the paper with input from all authors. The authors declare no competing interests.
Funding Information:
We thank I. Andrews for excellent technical assistance, K. Nave (Max Planck Institute for Experimental Medicine, Germany) for Nex Cre/+ mice, J. Burrone and B. Rico for critical reading of the manuscript, and members of the Marín and Rico laboratories for stimulating discussions and ideas. This work was supported by grants from the European Research Council ( ERC-2017-AdG 787355 ) and the European Union’s Horizon 2020 Research and Innovation Programme AIMS-2-TRIALS (777394) to O.M.
Publisher Copyright:
© 2022 The Authors
PY - 2022/7/5
Y1 - 2022/7/5
N2 - One key factor underlying the functional balance of cortical networks is the ratio of excitatory and inhibitory neurons. The mechanisms controlling the ultimate number of interneurons are beginning to be elucidated, but to what extent similar principles govern the survival of the large diversity of cortical inhibitory cells remains to be investigated. Here, we investigate the mechanisms regulating developmental cell death in neurogliaform cells, bipolar cells, and basket cells, the three main populations of interneurons originating from the caudal ganglionic eminence and the preoptic region. We found that all three subclasses of interneurons undergo activity-dependent programmed cell death. However, while neurogliaform cells and basket cells require glutamatergic transmission to survive, the final number of bipolar cells is instead modulated by serotonergic signaling. Together, our results demonstrate that input-specific modulation of neuronal activity controls the survival of cortical interneurons during the critical period of programmed cell death.
AB - One key factor underlying the functional balance of cortical networks is the ratio of excitatory and inhibitory neurons. The mechanisms controlling the ultimate number of interneurons are beginning to be elucidated, but to what extent similar principles govern the survival of the large diversity of cortical inhibitory cells remains to be investigated. Here, we investigate the mechanisms regulating developmental cell death in neurogliaform cells, bipolar cells, and basket cells, the three main populations of interneurons originating from the caudal ganglionic eminence and the preoptic region. We found that all three subclasses of interneurons undergo activity-dependent programmed cell death. However, while neurogliaform cells and basket cells require glutamatergic transmission to survive, the final number of bipolar cells is instead modulated by serotonergic signaling. Together, our results demonstrate that input-specific modulation of neuronal activity controls the survival of cortical interneurons during the critical period of programmed cell death.
KW - Apoptosis
KW - Cell Survival
KW - Cerebral Cortex
KW - Interneurons
KW - Neurons
UR - http://www.scopus.com/inward/record.url?scp=85133265130&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2022.111037
DO - 10.1016/j.celrep.2022.111037
M3 - Article
C2 - 35793629
SN - 2211-1247
VL - 40
SP - 111037
JO - Cell Reports
JF - Cell Reports
IS - 1
M1 - 111037
ER -