| The hippocampus is vital for memory formation, which depends critically on short term (lasting minutes or less) and long term (lasting 30 min to weeks) synaptic plasticity. Here, we describe a novel form of short-term plasticity in which synaptic efficacy depends exclusively on postsynaptic rate and explore the consequences of this phenomenon for long-term plasticity. We also examine the effects of action potential (AP) timing on input efficacy.; Patch clamp experiments were performed in CA1 pyramidal cells. We applied periodic current pulses to induce postsynaptic APs at a frequency (f) of 0.5 Hz--10 Hz. Following each AP by a time delay Deltat, we induced small (2--4 mV) EPSPs in the proximal dendrites by shocking the Schaffer collaterals. For f ≤ 1 Hz, EPSP magnitudes were 90% of baseline For f ≤ 5 Hz, EPSP magnitudes exceeded baseline amplitudes by approximately 20%, demonstrating that as firing rate increases, so does EPSP magnitude.; We have identified the mechanisms underlying rate-dependent EPSP magnitude: strychnine-sensitive glycine receptors, located post-synaptically, are open in the quiescent hippocampal brain slice and diminish the baseline EPSP by shunting the postsynaptic membrane. High rates of postsynaptic activity close these glycine receptors by increasing the activity of the glycine transporter, GlyT2, which reduces the amount of glycine available in the extracellular matrix, increasing EPSP magnitude by decreasing the number of open glycine receptors. Further, we have found that this increase in EPSP magnitude increases the amount of long term depression (LTD). This increase in LTD seems to be directly related to the glycine receptor activity, as increased depression is present in strychnine and diminished by inhibiting GlyT2. Finally, we investigated the effect of changing the delay Deltat, between the AP and EPSP. We find for short delays (1--20 ms), the EPSP is annihilated by the AP, which we believe is a result of the AP shunting the membrane. |
