Activity-dependent maintenance of long-term potentiation at visual cortical inhibitory synapses.
Neural activity producing a transient increase in intracellular Ca(2+) concentration can induce long-term potentiation (LTP) at visual cortical inhibitory synapses similar to those seen at various excitatory synapses. Here we report that low-frequency neural activity is required to maintain LTP at these inhibitory synapses. Inhibitory responses of layer 5 cells evoked by layer 4 stimulation were studied in developing rat visual cortical slices under a pharmacological blockade of excitatory synaptic transmission using intracellular and whole-cell recording methods. Although LTP induced by high-frequency stimulation (HFS) persisted while test stimulation was applied at 0.1 Hz, it was not maintained in approximately two-thirds of cells after test stimulation was stopped for 30 min. In the rest of the cells, LTP seemed to be maintained by spontaneous presynaptic spikes, because presynaptic inhibitory cells discharged spontaneously in our experimental condition and because LTP was totally abolished by a temporary application of Na(+) channel blockers. Experiments applying various Ca(2+) channel blockers and Ca(2+) chelators after HFS demonstrated that LTP maintenance was mediated by presynaptic Ca(2+) entries through multiple types of high-threshold Ca(2+) channels, which activated Ca(2+)-dependent reactions different from those triggering transmitter release. The Ca(2+) entries associated with action potentials seemed to be regulated by presynaptic K(+) channels, presumably large-conductance Ca(2+)-activated K(+) channels, because the application of blockers for these channels facilitated LTP maintenance. In addition, noradrenaline facilitated the maintenance of LTP. These findings demonstrate a new mechanism by which neural activity regulates the continuation and termination of LTP at visual cortical inhibitory synapses.
Komatsu
Y
Y
Department of Visual Neuroscience, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.komatsu@riem.nagoya-u.ac.jp
Yoshimura
Y
Y
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000502:physiology*; D009433:Neural Inhibition / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000378:metabolism; D017729:Presynaptic Terminals / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology; D026941:Sodium Channel Blockers; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014793:Visual Cortex / Q000502:physiology*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D026941:Sodium Channel Blockers; D012701:Serotonin; D009638:Norepinephrine