Labile glutamate signaling onto CA1 pyramidal cells in the developing hippocampus depends mechanistically on input...

The apical dendrite of hippocampal CA1 pyramidal cells receives information from the entorhinal cortex via the dentate gyrus and CA3 (Schaffer-collateral (SC) input) proximally within the stratum radiatum (SR) and directly from the entorhinal cortex/thalamus distally within the stratum lacunosum-moleculare (SLM). During the early postnatal development, very low/low frequency (0.033-1Hz) activation of previously non-stimulated (naïve) SC synapses (SR-CA1 synapses) results in a stimulus-, but not frequency-, dependent depression which is explained by postsynaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) silencing. This lability of AMPA signaling has been suggested to play a role in the activity-dependent organization of the SR synaptic input. Compared with the SR region the SLM region is matured earlier and may become organized in a different manner. Here, using field recordings of synaptic activity in hippocampal slices from 2nd postnatal week rats, we found that SLM-CA1 synapses are also readily depressed by activity in the very low/low frequency range (0.033-1Hz). The depression was, however, quite distinct from that of SR-CA1 synapses, being frequency dependent and reversing faster following stimulus interruption. Bath application of an AMPA receptor agonist produced only a small (-8%) post-application (10min) depression of SLM-CA1 synapses in contrast to that of SR-CA1 synapses (-33%). The SLM-CA1 synapses did also exhibit less long-term depression than the SR-CA1 synapses. We conclude that in the developing hippocampus the labile glutamate signaling onto CA1 pyramidal cell depends mechanistically on input pathway. The labile AMPA signaling at SLM-CA1 synapses is most likely explained by a presynaptic mechanism with limited amount of postsynaptic AMPA silencing.