PTHrP NLS and C terminus deficiency impairs hippocampal synaptic transmission and plasticity.

<p>(A) Attenuation of spontaneous AMPA receptor-mediated postsynaptic currents (AMPA EPSCs). CA1 neurons were recorded at a −70 mV holding potential in conventional whole-cell patch mode. Top: Representative traces from CA1 neurons of P14 WT and <i>Pthrp</i> KI hippocampus. Both the frequency and amplitude of AMPA EPSCs were decreased in <i>Pthrp</i> KI mice. Bottom: Cumulative distribution of AMPA EPSCs amplitude (mean±SE) in WT and <i>Pthrp</i> KI mice. (B) Attenuation of spontaneous NMDA receptor-mediated postsynaptic currents (NMDA EPSCs). Spontaneous NMDA EPSCs were recorded at +40 mV in whole-cell mode. Top: Representative traces from neurons of WT and <i>Pthrp</i> KI hippocampus. Both the frequency and amplitude of NMDA EPSCs were decreased in <i>Pthrp</i> KI mice. Bottom: Cumulative distribution of NMDA EPSCs amplitude in P14 WT and <i>Pthrp</i> KI mice. (C) Representative traces display evoked AMPA EPSCs and NMDA EPSCs when cells were held at −70 mV and +40 mV, respectively. (D) Summary of statistical results shows the attenuation of the AMPA/NMDA ratio in <i>Pthrp</i> KI mice. (E) Sample experiments display LTP recorded in hippocampal CA1 neurons in P14 WT and KI mice. (F) Summary data show impared LTP in <i>Pthrp</i> KI mice. Compared with WT control, the magnitude of LTP in <i>Pthrp</i> KI mice was significantly attenuated. LTP was produced with a pairing protocol. Each value is the mean±SEM of determinations in 5 mice of each group. ** <i>P</i><0.01, compared to wild-type littermates.