Network stability through homeostatic scaling of excitatory and inhibitory synapses following inactivity in CA3 of rat organotypic hippocampal slice cultures.
Homeostatic plasticity is a phenomenon whereby synaptic strength is scaled in the context of the activity that the network receives. Here, we have analysed excitatory and inhibitory synapses in a model of homeostatic plasticity where rat organotypic hippocampal slice cultures were deprived of excitatory synaptic input by the NMDA and AMPA/KA glutamate receptor antagonists, AP5 and CNQX. We show that chronic excitatory synapse deprivation generates an excitable CA3 network where enhanced amplitude and frequency of spontaneous excitatory post-synaptic potentials were associated with increased glutamate receptor subunit expression and increased number and size of synapsin 1 and VGLUT1 positive puncta. Intact spontaneous inhibitory post-synaptic potentials coincided with persistent expression of the GABA-A receptor alpha subunit and GAD65 and an enhancement of parvalbumin-positive puncta. In this model of homeostatic plasticity, scaling up of synaptic excitation and maintenance of fast synaptic inhibition promote an excitable, but stable, CA3 network.
Buckby
Lucy E
LE
School of Biological Sciences, Royal Holloway University of London, Egham, Surrey TW20 0EX, UK.
Jensen
Thomas P
TP
Smith
Paul J E
PJ
Empson
Ruth M
RM
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D006624:Hippocampus / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D006706:Homeostasis; D009415:Nerve Net / Q000033:anatomy & histology / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D046509:Tissue Culture Techniques; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000631:Aminopyridines; D015415:Biomarkers; D018691:Excitatory Amino Acid Antagonists; D018091:Receptors, AMPA; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; D050598:Vesicular Glutamate Transport Protein 1; D005680:gamma-Aminobutyric Acid; C409466:NR1 NMDA receptor; C493466:Slc17a7 protein, rat