Two different Ca2+-dependent inhibitory mechanisms of spontaneous firing by glutamate in dopamine neurons.
The excitatory neurotransmitter, glutamate, generates a characteristic burst-pause type of firing in midbrain dopamine neurons in association with the reward behavior, but the cellular mechanism by which glutamate generates these bursts is unknown. Here, we show that the bursts in spontaneously firing dopamine neurons can be generated by the combinative actions of the brief stimulatory and the subsequent Ca(2+)-dependent inhibitory signals in response to glutamate stimulation. The two Ca(2+)-dependent firing-extinction signals are activated by different glutamate receptors. Although the activation of metabotropic glutamate receptors rapidly stopped the enhanced firing through the Ca(2+) release from intracellular stores, the activation of NMDA and AMPA/kainate receptors abolished the firing immediately after termination of the stimulation due to the Ca(2+) accumulation in the cell. These two Ca(2+)-dependent inhibitory mechanisms appear to participate in the generation of characteristic bursts in dopamine neurons by controlling the maximum firing number of single bursts and the duration of post-firing pauses.
Kim
Shin Hye
SH
Department of Physiology and Medical Research Center for Regulation of Neuronal Cell Excitability, Center for Molecular Medicine, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Jangan-ku, Suwon, Korea.
Choi
Yu Mi
YM
Chung
Sungkwon
S
Uhm
Dae Yong
DY
Park
Myoung Kyu
MK
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D002478:Cells, Cultured; D004298:Dopamine / Q000378:metabolism*; D004558:Electric Stimulation; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism* / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D017470:Receptors, Glutamate; D018698:Glutamic Acid; D002118:Calcium; D004298:Dopamine