Contribution of NR2B subunits to synaptic transmission in amygdaloid interneurons.

Synaptic responses of interneurons in the rat lateral amygdala (LA) to electrical microstimulation of putative cortical and thalamic afferents were studied in slice preparations in situ. The EPSPs at both thalamic and cortical inputs were composed of two major components that were sensitive to 6,7-dinitroxaline-2,3-dione and DL-2-amino-5-phosphonovaleric acid (APV), indicating mediation through AMPA and NMDA receptors. NMDA receptor activation contributed to basal synaptic transmission, as evidenced through a reduction of EPSP amplitudes and integrals by APV. NMDA receptor-mediated postsynaptic currents showed magnesium-regulated voltage dependence, and current-voltage relationships displayed a region of negative slope conductance negative to resting potential. Deactivation of NMDA receptor-mediated currents followed a two exponential time course, with both components being significantly reduced by ifenprodil (10 microm), an antagonist of the NR2B subunit of NMDA receptors. Significant differences were not observed between NMDA currents or ifenprodil effects at thalamic and cortical inputs. Furthermore, recordings from a sample of projection neurons in the LA provided additional evidence for the existence of ifenprodil-sensitive components of thalamically and cortically evoked NMDA receptor-mediated responses. Immunohistochemical double-labeling and combined in situ hybridization/immunohistochemistry demonstrated that GABA-immunoreactive as well as GABA-negative cells express the NR2B subunit. Overall, these results show that GABAergic interneurons in the LA express functional NMDA receptors, which participate in basal synaptic transmission at both thalamic and cortical inputs. The finding that NR2B subunits are critically involved in NMDA receptor-mediated signaling at the two major input pathways to interneurons and projection cells in the LA is particularly interesting in the light of previous observations that NR2B antagonists interfere with plastic changes in the LA related to associative fear conditioning.