Control of excitatory and inhibitory synapse formation by neuroligins.
The normal function of neural networks depends on a delicate balance between excitatory and inhibitory synaptic inputs. Synapse formation is thought to be regulated by bidirectional signaling between pre- and postsynaptic cells. We demonstrate that members of the Neuroligin family promote postsynaptic differentiation in cultured rat hippocampal neurons. Down-regulation of neuroligin isoform expression by RNA interference results in a loss of excitatory and inhibitory synapses. Electrophysiological analysis revealed a predominant reduction of inhibitory synaptic function. Thus, neuroligins control the formation and functional balance of excitatory and inhibitory synapses in hippocampal neurons.
Chih
Ben
B
Department of Physiology and Cellular Biophysics, Center for Neurobiology and Behavior, Columbia University, New York, NY 10032, USA.
Engelman
Holly
H
Scheiffele
Peter
P
D000200:Action Potentials; D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal; D002460:Cell Line; D002478:Cells, Cultured; D003712:Dendrites / Q000502:physiology / Q000648:ultrastructure; D015536:Down-Regulation; D005071:Evoked Potentials; D019706:Excitatory Postsynaptic Potentials; D006624:Hippocampus / Q000166:cytology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009433:Neural Inhibition; D009474:Neurons / Q000502:physiology; D017729:Presynaptic Terminals / Q000502:physiology*; D020033:Protein Isoforms; D034622:RNA Interference; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013569:Synapses / Q000502:physiology*; D013570:Synaptic Membranes / Q000502:physiology*; D009435:Synaptic Transmission; D014162:Transfection; D050598:Vesicular Glutamate Transport Protein 1; D050495:Vesicular Inhibitory Amino Acid Transport Proteins
D015816:Cell Adhesion Molecules, Neuronal; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D050598:Vesicular Glutamate Transport Protein 1; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; C093438:neuroligin 1; C098003:neuroligin 2; C098004:neuroligin 3; C033652:postsynaptic density proteins; C493406:vesicular GABA transporter