Poster Sessions

Dev-11

Tsz Wan Ho

M. T. Ho, K..A. Pelkey , L. Topolnik, R. S. Petralia, K. Takamiya, J. Xia, R. L. Huganir, J.-C. Lacaille, C. J. McBain

Developmental expression of Ca2+-permeable AMPARs underlies depolarization-induced LTD (DiLTD) at mossy fiber-CA3 pyramid synapses

Mossy fiber (MF) synapses made by dentate gyrus granule cell axons convey the major extrinsic input from neocortex to hippocampal CA3 pyramidal cells (PYRs). Interestingly, MF–PYR synapses mature entirely postnatally. This feature provides an attractive model to probe for receptor changes during synapse development in a defined central pathway. The glutamate receptor 2 (GluR2) subunit dictates several AMPAR biophysical properties and interacts with various molecules implicated in receptor trafficking. Thus, the presence or absence of the GluR2 subunit greatly influences AMPAR and, hence, synaptic function. Typically GluR2-containing, Ca2+-impermeable channels (CI-AMPARs) prevail at synapses between mature principal neurons; however, emerging evidence indicates that GluR2-lacking, Ca2+-permeable (CP)-AMPARs may be synaptically expressed by principal neurons early in development. In the current study we investigated whether native CP-AMPARs contribute to basal transmission and synaptic plasticity at developing MF–PYR synapses. We found that transmission at nascent MF–PYR synapses is mediated by a mixed population of CP- and CI-AMPARs as evidenced by a polyamine-dependent inwardly rectifying I–V relationship. Strikingly, MF–PYR transmission via CP-AMPARs is selectively depressed during depolarization-induced long-term depression (DiLTD), a postsynaptic form of MF–PYR plasticity observed only at young MF–PYR synapses. Indeed, postsynaptic CP-AMPAR-mediated Ca2+ transients (CaTs) at MF–PYR contacts in acute hippocampal slices were depressed to 6.5 +/- 3.4% of baseline responses after DiLTD induction. Moreover, DiLTD results in a reduced rectification of MF–PYR synaptic currents indicating that transmission becomes primarily supported by CI-AMPARs following DiLTD. Furthermore, we found that the PDZ-domain containing protein - PICK1 regulates the expression of CP-AMPARs at immature MF-PYR synapses. Interestingly, DiLTD was absent in young PICK1 knock-out mice, further supporting the preferential targeting of CP-AMPARs during DiLTD. Together, our findings indicate that the transient participation of CP-AMPARs at young MF–PYR synapses dictates the developmental window to observe DiLTD. In addition, the data support a general model involving the transient expression of CP-AMPARs during synapse development.