Repetitive activation of glutamatergic inputs evokes a long-lasting excitation in rat globus pallidus neurons in vitro.
External globus pallidus (GPe) neurons express abundant metabotropic glutamate receptor 1 (mGluR1) in their somata and dendrites and receive glutamatergic inputs mainly from the subthalamic nucleus. We investigated whether synaptically released glutamate could activate mGluR1s using whole cell and cell-attached recordings in rat brain slice preparations. Repetitive internal capsule stimulation evoked EPSPs followed by a slow depolarizing response (sDEPO) lasting 10-20 s. Bath application of both GABA(A) and GABA(B) receptor antagonists increased the amplitude of sDEPOs. A mixture of AMPA/kainate and N-methyl-d-aspartate receptor antagonists did not alter sDEPOs. The induction of sDEPOs was only partially mediated by mGluR1 because mGluR1 antagonists reduced but failed to completely block the responses. Voltage-clamp recordings revealed that slow inward currents sensitive to mGluR1 antagonist were larger at -60 than at -100 mV, whereas the currents insensitive to mGluR1 antagonist were larger at -100 than at -60 mV. In cell-attached recordings, repetitive internal capsule stimulation evoked long-lasting excitations in GPe neurons, which were also partially suppressed by mGluR1 antagonists. Application of a glutamate uptake inhibitor or an mGluR1 agonist significantly increased the spontaneous firing rate but decreased the excitations to repetitive stimulation. These results suggest that synaptically released glutamate can activate mGluR1, contributing to the induction of long-lasting excitation in GPe neurons and that background mGluR1 activation suppresses the slow mGluR1 responses. Thus mGluR1 may play important roles in the control of GPe neuronal activity.
Kaneda
Katsuyuki
K
Department of Anatomy and Neurobiology, College of Medicine, The University of Tennessee-Memphis, 855 Monroe Avenue, Memphis, TN 38163, USA.
Kita
Takako
T
Kita
Hitoshi
H
D000818:Animals; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology; D005917:Globus Pallidus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020531:Subthalamic Nucleus / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D018698:Glutamic Acid