Presynaptic mitochondria regulate activity-dependent regulation of synaptic transmission, called  short-term plasticity (STP), by supplying energy and buffering presynaptic Ca2+ concentration,. While Ca2+ is the most versatile intracellular signaling molecule, it may lead to cell death at very high concentration. Presynaptic mitochondria are frequently exposed to highest cytosolic [Ca2+]. Mitochondrial dysfunction is a key step in pathogenesis of most neurodegenerative disorders. Normal mitochondrial function depends on polarization of mitchondrial membrane. The earliest sign of mitochondrial dysfunction is their mild depolarization. Because mild mitochondrial depolarization blocks the primary Ca2+ release pathway from mitochondria, called mNCX, , it is possible that alteration in mitochondria-dependent presynaptic STP may provide the earliest sign for most neurodegenerative disorders. Accordingly, we have previously shown that mild depolarization of mitochondria and loss of post-tetanic potentiation (PTP, one of STP types) are the earliest signs detected in the Alzheimer’s model mice (Lee et al. 2012). In the present study, we identified the synapse types at which PTP depends on mitochondria among intracortical excitatory synapses. Given that mitochondrial involvement in PTP is synapse-type specific, the present study would provide a knowledge base for comprehending synaptic mechanisms that underlie the initial clinical signs of neurodegenerative disorders.