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Synaptic transmission is highly dynamic, especially during periods of repetitive activity. This short-term synaptic plasticity, elicited by either pairs or short trains of action potentials at moderate frequencies (1–10 Hz), may give rise to either depression or facilitation of synaptic transmission. We analyzed these processes in isolated, synaptically coupled pairs of inhibitory or excitatory neurons grown in low-density cultures of hippocampal neurons. Most inhibitory and excitatory synapses in these cultures displayed paired pulse depression, although the responses of excitatory synapses were more variable and occasionally facilitation was seen. With tetanic stimuli, inhibitory synapses showed depression, but excitatory synapses showed a much richer repertoire of behaviors, including depression and facilitation. While many inhibitory synapses showed posttetanic depression following short trains of action potentials, excitatory synapses instead showed posttetanic facilitation. This facilitation is accompanied by an increase in paired pulse ratio, suggesting that it is the result of presynaptic mechanisms. Finally, excitatory synapses often displayed paired pulse and tetanic facilitation of asynchronous release, a process not seen in inhibitory synapses in these cultures. These similarities and differences in short-term plasticity exhibited by inhibitory and excitatory cells are likely to be critical for information processing and the control of neuronal excitability, under both normal and pathological conditions, such as epilepsy. Synapse 50:41–52, 2003. © 2003 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]