TY - JOUR
T1 - Npas4 regulates excitatory-inhibitory balance within neural circuits through cell-type-specific gene programs
AU - Spiegel, Ivo
AU - Mardinly, Alan R.
AU - Gabel, Harrison W.
AU - Bazinet, Jeremy E.
AU - Couch, Cameron H.
AU - Tzeng, Christopher P.
AU - Harmin, David A.
AU - Greenberg, Michael E.
N1 - Funding Information:
We thank F. Polleux and J. De Marchena for help with establishing the MGE cultures, C. Mandel-Brehm and C. Chen for help with electrophysiology experiments, J.M. Gray and A.M. Costa for help with preparing RNA-seq libraries, B.L. Bloodgood for preliminary recordings from MGE cultures, N. Sharma for the lentiviral expression construct of Npas4, E. Griffith and T. Cherry for critical reading of the manuscript, and P. Zhang for managing the mouse colony. This work was funded by fellowships by the Human Frontiers Science Program and the Swiss National Science Foundation (I.S.) and the National Institutes of Health grant NS048276 (M.E.G.).
PY - 2014/5/22
Y1 - 2014/5/22
N2 - The nervous system adapts to experience by inducing a transcriptional program that controls important aspects of synaptic plasticity. Although the molecular mechanisms of experience-dependent plasticity are well characterized in excitatory neurons, the mechanisms that regulate this process in inhibitory neurons are only poorly understood. Here, we describe a transcriptional program that is induced by neuronal activity in inhibitory neurons. We find that, while neuronal activity induces expression of early-response transcription factors such as Npas4 in both excitatory and inhibitory neurons, Npas4 activates distinct programs of late-response genes in inhibitory and excitatory neurons. These late-response genes differentially regulate synaptic input to these two types of neurons, promoting inhibition onto excitatory neurons while inducing excitation onto inhibitory neurons. These findings suggest that the functional outcomes of activity-induced transcriptional responses are adapted in a cell-type-specific manner to achieve a circuit-wide homeostatic response.
AB - The nervous system adapts to experience by inducing a transcriptional program that controls important aspects of synaptic plasticity. Although the molecular mechanisms of experience-dependent plasticity are well characterized in excitatory neurons, the mechanisms that regulate this process in inhibitory neurons are only poorly understood. Here, we describe a transcriptional program that is induced by neuronal activity in inhibitory neurons. We find that, while neuronal activity induces expression of early-response transcription factors such as Npas4 in both excitatory and inhibitory neurons, Npas4 activates distinct programs of late-response genes in inhibitory and excitatory neurons. These late-response genes differentially regulate synaptic input to these two types of neurons, promoting inhibition onto excitatory neurons while inducing excitation onto inhibitory neurons. These findings suggest that the functional outcomes of activity-induced transcriptional responses are adapted in a cell-type-specific manner to achieve a circuit-wide homeostatic response.
UR - http://www.scopus.com/inward/record.url?scp=84901323269&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2014.03.058
DO - 10.1016/j.cell.2014.03.058
M3 - Article
C2 - 24855953
AN - SCOPUS:84901323269
SN - 0092-8674
VL - 157
SP - 1216
EP - 1229
JO - Cell
JF - Cell
IS - 5
ER -