A limited role of NKCC1 in telencephalic glutamatergic neurons for developing hippocampal network dynamics and behavior
04/06/2021
A limited role of NKCC1 in telencephalic glutamatergic neurons for developing hippocampal network dynamics and behavior
Jürgen Grafa, Chuanqiang Zhanga, Stephan Lawrence Marguetb, Tanja Herrmannd, Tom Flossmanna, Robin Hinschb, Vahid Rahmatie, Madlen Guenthera, Christiane Frahma, Anja Urbacha, Ricardo Melo Nevesb, Otto W. Wittea, Stefan J. Kiebele, Dirk Isbrandtb, Christian A. Hübnerd, Knut Holthoffa, Knut Kirmse (2021)
PNAS 2021 118 (14) e2014784118
NKCC1 is the primary transporter mediating chloride uptake in immature principal neurons, but its role in the development of in vivo network dynamics and cognitive abilities remains unknown. Here, we address the function of NKCC1 in developing mice using electrophysiological, optical, and behavioral approaches. We report that NKCC1 deletion from telencephalic glutamatergic neurons decreases in vitro excitatory actions of γ-aminobutyric acid (GABA) and impairs neuronal synchrony in neonatal hippocampal brain slices. In vivo, it has a minor impact on correlated spontaneous activity in the hippocampus and does not affect network activity in the intact visual cortex. Moreover, long-term effects of the developmental NKCC1 deletion on synaptic maturation, network dynamics, and behavioral performance are subtle. Our data reveal a neural network function of NKCC1 in hippocampal glutamatergic neurons in vivo, but challenge the hypothesis that NKCC1 is essential for major aspects of hippocampal development.
