Theta-frequency facilitation of AMPA receptor-mediated synaptic currents in the principal cells of the medial septum.
Recent evidence suggests that Ca(2+)-permeable AMPA receptors display rapid, short-lasting current facilitation. In this study, we investigated the properties of AMPA receptor-mediated synaptic currents in medial septal neurons of the rat in an in vitro slice preparation. Immunocytochemistry with a selective antibody to the GluR2 subunit revealed that both choline acetyltransferase-containing and parvalbumin-containing neurons of the medial septum express no detectable GluR2 subunit immunoreactivity. We used whole cell voltage-clamp recordings to measure synaptically evoked AMPA receptor-mediated currents from medial septal neurons following stimulation of midline afferents. The GYKI 52466 (50 microM)- and 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide (NBQX) (20 microM)-sensitive AMPA receptor-mediated component of the synaptic response was isolated by blocking GABA(A)- and N-methyl-D-aspartate receptor-mediated currents with 30 microM bicuculline and 100 microM 2-amino-5-phosphonovaleric acid, respectively. In some cases, patched cells were filled with Lucifer yellow (0.1%) and imaged using 2-photon laser scanning microscopy. AMPA receptor-mediated currents that were observed in large medial septal neurons (20--30 microm) displayed rectification. These currents were sensitive to external application of philanthotoxin-343 (PhTx-343, 50 microM), a potent, high-affinity antagonist of Ca(2+)-permeable, GluR2-lacking AMPA receptors. Rectifying AMPA receptor-mediated currents also displayed a rapid increase in amplitude when evoked five times at low frequency such as 6 Hz. In contrast to currents observed in large medial septal neurons, AMPA-receptor mediated currents evoked in the remaining small (8--11 microm) neurons were nonrectifying and displayed rapid synaptic depression when stimulated five times at 6 Hz. The currents evoked in these cells were unaffected by external application of PhTx-343 and were therefore GluR2-containing AMPA receptors. The results of the present study demonstrate that the principal projection neurons of the medial septum contain PhTx-343-sensitive, GluR2-lacking AMPA receptors that display rapid current facilitation when stimulated at low frequencies.
Armstrong
J N
JN
Neuroscience Research Group, Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
MacVicar
B A
BA
D000818:Animals; D048429:Cell Size; D004553:Electric Conductivity; D004558:Electric Stimulation; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism / Q000502:physiology*; D012688:Septum Pellucidum / Q000166:cytology / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D013826:Theta Rhythm
D018091:Receptors, AMPA; C104722:glutamate receptor ionotropic, AMPA 2