Absence of long-term depression in the visual cortex of glutamic Acid decarboxylase-65 knock-out mice.
Long-term depression (LTD) is widely considered a mechanism for experience-induced synaptic weakening in the brain. Recent in vivo studies on glutamic acid decarboxylase [GAD 65 (-/-)] knock-out mice indicates that GABAergic synaptic inhibition is also required for the normal weakening of deprived inputs in the visual cortex. To better understand how GABAergic inhibition might control plasticity, we assessed the status of synaptic inhibition and LTD in visual cortical slices of GAD 65 knock-out mice. We found the following: (1) the efficacy of GABAergic synapses during repetitive activation is reduced in GAD 65 (-/-) mice; (2) the induction of LTD is impaired in the visual cortex of GAD 65 (-/-) mice; and (3) chronic, but not acute, treatment with the benzodiazepine agonist diazepam restores LTD in GAD 65 (-/-) mice. These results suggest that a certain inhibitory tone is required for the induction of LTD in visual cortex. We propose that the lack of visual cortical LTD in GAD 65 (-/-) may account for the lack of experience-dependent plasticity in these mice.
Choi
Se-Young
SY
Department of Neuroscience and Howard Hughes Medical Institute, Mind Brain Institute, Johns Hopkins University, Baltimore, Maryland 21218, USA.
Morales
Bernardo
B
Lee
Hey-Kyoung
HK
Kirkwood
Alfredo
A
D000818:Animals; D046508:Culture Techniques; D003975:Diazepam / Q000494:pharmacology; D005074:Evoked Potentials, Visual; D019706:Excitatory Postsynaptic Potentials; D018757:GABA Modulators / Q000494:pharmacology; D005968:Glutamate Decarboxylase / Q000235:genetics* / Q000502:physiology*; D007527:Isoenzymes / Q000235:genetics* / Q000502:physiology*; D007700:Kinetics; D051379:Mice; D018345:Mice, Knockout; D009473:Neuronal Plasticity; D009435:Synaptic Transmission; D014793:Visual Cortex / Q000201:enzymology* / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018757:GABA Modulators; D007527:Isoenzymes; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2; D003975:Diazepam