RT Journal Article SR Electronic T1 Retrograde Suppression of Post-Tetanic Potentiation at the Mossy Fiber-CA3 Pyramidal Cell Synapse JF eneuro JO eNeuro FD Society for Neuroscience SP ENEURO.0450-20.2021 DO 10.1523/ENEURO.0450-20.2021 VO 8 IS 2 A1 Makani, Sachin A1 Lutzu, Stefano A1 Lituma, Pablo J. A1 Hunt, David L. A1 Castillo, Pablo E. YR 2021 UL http://www.eneuro.org/content/8/2/ENEURO.0450-20.2021.abstract AB In the hippocampus, the excitatory synapse between dentate granule cell (GC) axons, or mossy fibers (MFs), and CA3 pyramidal cells (MF-CA3) expresses robust forms of short-term plasticity, such as frequency facilitation and post-tetanic potentiation (PTP). These forms of plasticity are due to increases in presynaptic neurotransmitter release, and can be engaged when dentate GCs fire in bursts (e.g., during exploratory behaviors) and bring CA3 pyramidal neurons above threshold. While frequency facilitation at this synapse is limited by endogenous activation of presynaptic metabotropic glutamate receptors (mGluRs), whether MF-PTP can be regulated in an activity-dependent manner is unknown. Here, using physiologically relevant patterns of MF stimulation in acute mouse hippocampal slices, we found that disrupting postsynaptic Ca2+ dynamics increases MF-PTP, strongly suggesting a form of Ca2+-dependent retrograde suppression of this form of plasticity. PTP suppression requires a few seconds of MF bursting activity and Ca2+ release from internal stores. Our findings raise the possibility that the powerful MF-CA3 synapse can negatively regulate its own strength not only during PTP-inducing activity typical of normal exploratory behaviors, but also during epileptic activity.