Group I metabotropic glutamate receptors activate burst firing in rat midbrain dopaminergic neurons.
We have investigated the changes in the spontaneous firing pattern induced by DHPG ((S)-3,5-dihydroxyphenylglycine) and NMDA (N-methyl-d-aspartic acid) on rat dopaminergic neurons in substantia nigra pars compacta (SNc) using sharp microelectrode recordings in in vitro conditions. Twenty-five out of 33 cells modified the regular single-pacemaker activity in burst firing when exposed to the Group I metabotropic glutamate receptor (mGluR) agonist DHPG (30 microM) and d-tubocurarine (500 microM) (d-TC), whereas they all fired in bursts during NMDA (20 microM) plus d-TC application. The blockade of SK-channels by d-TC and apamin was essential for the production of both types of bursts. Although the two drugs induced a similar number of action potentials per burst, the DHPG-induced bursts had a lower frequency, a longer duration and a longer plateau period without spikes. In addition, the DHPG-induced bursting had a longer wash-out, could be reduced or blocked by the mGluR 1 selective, non-competitive antagonist CPCCOEt (7-cyclopropan[b]chromen-1a-carboxylic acid ethyl ester) (100 microM) while it was not affected by the mGluR 5 selective antagonist MPEP (2-methyl-6-(phenylethynyl)-pyridine (10 microM). These results suggest that both the activation of glutamate metabotropic type 1 and NMDA ionotropic receptors induce burst firing in the dopaminergic cells of the ventral midbrain when the activity of the SK-channels is reduced.
Prisco
Simonetta
S
IRCCS Fondazione S. Lucia, Experimental Neurology Laboratory, Via Ardeatina 306, 00179 Rome, Italy.
Natoli
Silvia
S
Bernardi
Giorgio
G
Mercuri
Nicola B
NB
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D004298:Dopamine / Q000502:physiology*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D008636:Mesencephalon / Q000187:drug effects / Q000502:physiology*; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives* / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D014403:Tubocurarine / Q000494:pharmacology
D018690:Excitatory Amino Acid Agonists; D018733:Nicotinic Antagonists; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D008734:Methoxyhydroxyphenylglycol; D016202:N-Methylaspartate; C010117:3,4-dihydroxyphenylglycol; D004298:Dopamine; D014403:Tubocurarine