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Synaptic fatigue refers to a temporary reduction in the ability of a synapse to transmit signals due to the depletion of neurotransmitters after prolonged or repeated stimulation. When a neuron is highly active for an extended period, its supply of neurotransmitters can diminish, leading to a weaker synaptic response until the neurotransmitter levels are replenished. This helps prevent overstimulation and allows the synapse to recover.