Homeostatic synapse-driven membrane plasticity in nucleus accumbens neurons.
Stable brain function relies on homeostatic maintenance of the functional output of individual neurons. In general, neurons function by converting synaptic input to output as action potential firing. To determine homeostatic mechanisms that balance this input-output/synapse-membrane interaction, we focused on nucleus accumbens (NAc) neurons and demonstrated a novel form of synapse-to-membrane homeostatic regulation, homeostatic synapse-driven membrane plasticity (hSMP). Through hSMP, NAc neurons adjusted their membrane excitability to functionally compensate for basal shifts in excitatory synaptic input. Furthermore, hSMP was triggered by synaptic NMDA receptors (NMDARs) and expressed by the modification of SK-type Ca(2+)-activated potassium channels. Moreover, hSMP in NAc neurons was abolished in rats during a short- (2 d) or long- (21 d) term withdrawal from repeated intraperitoneal injections of cocaine (15 mg/kg/d, 5 d). These results suggest that hSMP is a novel form of synapse-to-membrane homeostatic plasticity and dysregulation of hSMP may contribute to cocaine-induced cellular alterations in the NAc.
Program in Neuroscience, Washington State University, Pullman, Washington 99164-6520, USA.
Masago
M
Ishikawa
Ping
P
Mu
Jason T
JT
Moyer
John A
JA
Wolf
Raymond M
RM
Quock
Neal M
NM
Davies
Xiu-Ti
XT
Hu
Oliver M
OM
Schlüter
Yan
Y
Dong
D000818:Animals; D001030:Apamin / Q000494:pharmacology; D001703:Biophysics; D003042:Cocaine / Q000494:pharmacology; D000076122:Disks Large Homolog 4 Protein; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D018942:Macrolides / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009714:Nucleus Accumbens / Q000166:cytology*; D010455:Peptides / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D034622:RNA Interference / Q000502:physiology; D034741:RNA, Small Interfering; D051381:Rats; D017207:Rats, Sprague-Dawley; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D046509:Tissue Culture Techniques; D014161:Transduction, Genetic / Q000379:methods
D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D018765:Dopamine Uptake Inhibitors; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D047908:Intracellular Signaling Peptides and Proteins; D018942:Macrolides; D008565:Membrane Proteins; D010455:Peptides; D026902:Potassium Channel Blockers; D034741:RNA, Small Interfering; D051640:Small-Conductance Calcium-Activated Potassium Channels; D049452:Green Fluorescent Proteins; D001030:Apamin; C064719:iberiotoxin; D003042:Cocaine