Fig. 5
Aβ-mediated neuronal hyperactivity depends on the elevated somatic NMDAR activation. a Synthetic human Aβ1–42 peptide oligomerization was confirmed by Western blots. Aβ42–1 peptide was used as a control. b Example traces showing the spontaneous firing of recorded CA1 pyramidal neurons before (RMP = − 65.97 mV) and after (RMP = − 60.89 mV) Aβ1–42 peptide (500 nM) treatment for 2 h. A dramatic enhancement of firing rate of hippocampal CA1 pyramidal neurons was observed in the Aβ-incubated slices. c The increased neuronal firing was reduced to the baseline level by locally applying an open NMDAR antagonist memantine (0.1 mM) to the soma of the recorded neuron. RMP was − 57.53 mV before memantine treatment and − 59.23 mV after memantine treatment. d Cumulative distribution of ISIs. e Statistical histogram showing that memantine significantly suppressed the Aβ1–42–induced enhancement of firing rate. **P < 0.01. f–h Same as in (c–e) except that ifenprodil (3 μM) was locally applied to the soma of recorded neurons. RMP was − 56.62 mV before ifenprodil treatment and − 65.24 mV after ifenprodil treatment. i Representative traces showing a dramatic increase in single NMDAR opening in the control, TBOA- or Aβ1–42-treated hippocampal pyramidal neurons. Cell-attached single-channel recording configuration was employed to record opening of NMDARs located on the soma of the recorded neuron. j Statistical histogram showing that both TBOA and Aβ1–42 dramatically elevated the open probability of somatic NMDARs. Data are means ± SEM, **P < 0.01, t test