Figure 7.

Mechanisms underlying the reduced NMDAR activation in Ts65Dn mice. A, Schematic drawing of SC-activated synapses onto CA1 pyramidal cells. B, Brief burst activation of SC inputs engages a positive feedback loop between membrane depolarization and voltage-dependent NMDAR activation in CA1-pyramidal cell dendrites of WT mice. This positive feedback is regulated by α5-GABAR-mediated voltage-dependent inhibition. C, Both increased dendritic inhibition and reduced NMDAR expression disrupt NMDAR activation in Ts65Dn mice. D, Application of the α5-NAM reduces dendritic inhibition and restores dendritic E/I balance to enable normal NMDAR activation in Ts65Dn mice.