Adaptation to synaptic inactivity in hippocampal neurons.
In response to activity deprivation, CNS neurons undergo slow adaptive modification of unitary synaptic transmission. The changes are comparable in degree to those induced by brief intense stimulation, but their molecular basis is largely unknown. Our data indicate that prolonged AMPAR blockade acts through loss of Ca2+ entry through L-type Ca2+ channels to bring about an increase in both vesicle pool size and turnover rate, as well as a postsynaptic enhancement of the contribution of GluR1 homomers, concentrated at the largest synapses. The changes were consistent with a morphological scaling of overall synapse size, but also featured a dramatic shift toward synaptic drive contributed by the Ca2+-permeable homomeric GluR1 receptors. These results extend beyond "synaptic homeostasis" to involve more profound changes that can be better described as "metaplasticity".
Thiagarajan
Tara C
TC
Department of Molecular and Cellular Physiology, Beckman Center, Stanford University School of Medicine, Stanford, California 94305, USA.
Lindskog
Maria
M
Tsien
Richard W
RW
D000222:Adaptation, Physiological / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D015153:Blotting, Western; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D007150:Immunohistochemistry; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011073:Polyamines / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D051381:Rats; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000378:metabolism; D017661:Receptors, Presynaptic / Q000187:drug effects / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D014162:Transfection
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D011073:Polyamines; D018091:Receptors, AMPA; D017661:Receptors, Presynaptic; C034092:delta-philanthotoxin