Activity-dependent tuning of inhibitory neurotransmission based on GABAAR diffusion dynamics.
An activity-dependent change in synaptic efficacy is a central tenet in learning, memory, and pathological states of neuronal excitability. The lateral diffusion dynamics of neurotransmitter receptors are one of the important parameters regulating synaptic efficacy. We report here that neuronal activity modifies diffusion properties of type-A GABA receptors (GABA(A)R) in cultured hippocampal neurons: enhanced excitatory synaptic activity decreases the cluster size of GABA(A)Rs and reduces GABAergic mIPSC. Single-particle tracking of the GABA(A)R gamma2 subunit labeled with quantum dots reveals that the diffusion coefficient and the synaptic confinement domain size of GABA(A)R increases in parallel with neuronal activity, depending on Ca(2+) influx and calcineurin activity. These results indicate that GABA(A)R diffusion dynamics are directly linked to rapid and plastic modifications of inhibitory synaptic transmission in response to changes in intracellular Ca(2+) concentration. This transient activity-dependent reduction of inhibition would favor the onset of LTP during conditioning.
Bannai
Hiroko
H
Biologie Cellulaire de la Synapse N&P, Ecole Normale Supérieure Paris, INSERM U789, 46 Rue d'Ulm 75005 Paris, France.
Lévi
Sabine
S
Schweizer
Claude
C
Inoue
Takafumi
T
Launey
Thomas
T
Racine
Victor
V
Sibarita
Jean-Baptiste
JB
Mikoshiba
Katsuhiko
K
Triller
Antoine
A
D000818:Animals; D000831:Animals, Newborn; D019921:Biotinylation / Q000379:methods; D019703:Calcineurin / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D004558:Electric Stimulation / Q000379:methods; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D036881:Long-Term Synaptic Depression / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D011724:Pyridazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D016704:Synapsins / Q000378:metabolism; D046509:Tissue Culture Techniques
D002352:Carrier Proteins; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D008565:Membrane Proteins; D011724:Pyridazines; D011963:Receptors, GABA-A; D016704:Synapsins; C073441:gephyrin; D016202:N-Methylaspartate; C049853:gabazine; D019703:Calcineurin; D002118:Calcium