ER vesicles and mitochondria move and communicate at synapses

Endoplasmic reticulum (ER) and mitochondria are multifunctional cell organelles and their involvement in Ca2+ handling is important in various neural activities. In the respiratory neurons, we observed ER as continuous reticulum in the soma and as isolated vesicles in dendrites. The vesicles moved bidirectionally with intermittent stops and decreased their velocity near exocytotic sites. ER vesicles and mitochondria that resided in these regions changed lumenal Ca2+ and mitochondrial potential in concert with synaptic activity. Ca2+ release from ER or mitochondria evoked exocytosis. ER vesicles and mitochondria bidirectionally exchanged Ca2+, the efficacy of which depended on the distance between organelles. Depolarisation-evoked exocytosis had different kinetics, depending on whether functional ER vesicles and mitochondria were present in perisynaptic regions and able to exchange Ca2+ or only one organelle type was available. Transfer of Ca2+ from ER to mitochondria produced long-lasting elevations of residual Ca2+ that increased the duration of exocytosis. In slice preparations, synaptic currents in inspiratory neurons were suppressed after disengagement of ER vesicles and mitochondria, and the activity was potentiated after stimulation of Ca2+ exchange between the organelles. We propose that communication between perisynaptic ER vesicles and mitochondria can shape intracellular Ca2+ signals and modulate synaptic and integrative neural activities.