Some of the features of neuronal synaptic transmission that can be modified over the short and long term include changes in presynaptic calcium levels, changes in vesicle numbers and probability of release, and alterations in postsynaptic receptor numbers and function. Such variations account in part for the synaptic plasticity that may underlie learning and memory. Alterations in levels of activity at the synapse require energy and other mitochondrial activities, and therefore mitochondria influence synaptic events by changes in mitochondrial targeting, shape, size and metabolic efficiency. Bcl-2 family proteins, by their actions at mitochondrial membranes, normally play an important role in cell death at the soma, but also strengthen or weaken synaptic connections. Mitochondria also regulate key metabolic events including protein and lipid synthesis required for synaptic plasticity.
Thus the actions of mitochondria at synaptic sites position these organelles to influence physiological and pathological changes in the brain. In neurodegenerative diseases, proteins that control mitochondrial ion channel activity may be key in deciding whether a synapse will live or die, and thereby whether a neuron will survive or undergo untimely death. In neurodevelopmental disease, mitochondrial metabolic changes are required for critical periods in brain and synaptic development.
Specialized Terms: Brain ischemia; Neurodegeneration; Neurodevelopment; Parkinson's Disease; Fragile X Disorder; Autism; Mitochondrial ion channels; Cell death; synaptic transmission; synaptic plasticity; ATP synthase; mitochondrial permeability transition pore (mPTP).
Endocrinology; Mitochondria; Nervous System; Synaptic Transmission; Neurobiology; Apoptosis