Photolysis of postsynaptic caged Ca²⁺ can potentiate and depress mossy fiber synaptic responses in rat hippocampal CA3 pyramidal neurons. J Neurophysiol vv: pppp-pppp, yyyy. First published Month dd, yyyy; DOI. The induction of mossy fiber-CA3 long-term potentiation (LTP) and depression (LTD) has been variously described as being dependent on either pre- or postsynaptic factors. Some of the postsynaptic factors for LTP induction include ephrin-B receptor tyrosine kinases and a rise in postsynaptic Ca²⁺ ([Ca²⁺]_i). Ca²⁺ is also believed to be involved in the induction of the various forms of LTD at this synapse. We used photolysis of caged Ca²⁺ compounds to test whether a postsynaptic rise in [Ca²⁺]_i is sufficient to induce changes in synaptic transmission at mossy fiber synapses onto rat hippocampal CA3 pyramidal neurons. We were able to elevate postsynaptic [Ca²⁺]_i to approximately 1 µM for a few seconds in pyramidal cell somata and dendrites. We estimate that CA3 pyramidal neurons have approximately five-fold greater endogenous Ca²⁺ buffer capacity than CA1 neurons, limiting the rise in [Ca²⁺]_i achievable by photolysis. This [Ca²⁺]_i rise induced either a potentiation or a depression at mossy fiber synapses in different preparations. Neither the potentiation nor the depression was accompanied by consistent changes in paired-pulse facilitation, suggesting that these forms of plasticity may be distinct from synaptically induced LTP and LTD at this synapse. Our results are consistent with a postsynaptic locus for the induction of at least some forms of synaptic plasticity at mossy fiber synapses.