RT Journal Article
SR Electronic
T1 Epileptogenesis <em>In Vivo</em> Enhances the Sensitivity of Inhibitory Presynaptic Metabotropic Glutamate Receptors in Basolateral Amygdala Neurons <em>In Vitro</em>
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 983
OP 995
DO 10.1523/JNEUROSCI.17-03-00983.1997
VO 17
IS 3
A1 Volker Neugebauer
A1 N. Bradley Keele
A1 Patricia Shinnick-Gallagher
YR 1997
UL http://www.jneurosci.org/content/17/3/983.abstract
AB Modulation of excitatory synaptic transmission by presynaptic metabotropic glutamate receptors (mGluRs) was examined in brain slices from control rats and rats with amygdala-kindled seizures. Using whole-cell voltage-clamp and current-clamp recordings, this study shows for the first time that in control and kindled basolateral amygdala neurons, two pharmacologically distinct presynaptic mGluRs mediate depression of synaptic transmission. Moreover, in kindled neurons, agonists at either group II- or group III-like mGluRs exhibit a 28- to 30-fold increase in potency and suppress synaptically evoked bursting. The group II mGluR agonist (2S,3S,4S)-2-(carboxycyclopropyl)glycine (l-CCG) dose-dependently depressed monosynaptic EPSCs evoked by stimulation in the lateral amygdala with EC50values of 36 nm (control) and 1.2 nm (kindled neurons). The group III mGluR agonistl-2-amino-4-phosphonobutyrate (l-AP4) was less potent, with EC50 values of 297 nm (control) and 10.8 nm (kindled neurons). The effects ofl-CCG and l-AP4 were fully reversible. Neitherl-CCG (0.0001–10 μm) nor l-AP4 (0.001–50 μm) caused membrane currents or changes in the current–voltage relationship. The novel mGluR antagonists (2S,3S,4S)-2-methyl-2-(carboxycyclopropyl)-glycine (MCCG; 100 μm) and (S)-2-methyl-2-amino-4-phos-phonobutyrate (MAP4; 100 μm) selectively reversed the inhibition byl-CCG and l-AP4 to 81.3 ± 12% and 65.3 ± 6.6% of predrug, respectively. MCCG and MAP4 (100–300 μm) themselves did not significantly affect synaptic transmission. The exquisite sensitivity of agonists in the kindling model of epilepsy and the lack of evidence for endogenous receptor activation suggest that presynaptic group II- and group III-like mGluRs might be useful targets for suppression of excessive synaptic activation in neurological disorders such as epilepsy.