Divergent interplay between STIM1 and STIM2 sets the efficacy of central synapses.

STIM1 and STIM2 differentially regulate synaptic efficacy, with STIM1 mainly supporting excitatory and STIM2 critical for inhibitory synapses in hippocampal neurons.

• Why it matters: Understanding how STIM isoforms influence neurotransmission is important because their roles in synaptic function are not well defined, which limits knowledge of calcium regulation in neural communication.
• What they did: The study used Ca 2+ imaging and electrophysiology in hippocampal neurons lacking STIM1, STIM2, or both, to analyze presynaptic and postsynaptic functions at excitatory and inhibitory synapses.
• The result: Both isoforms redundantly activated store-operated Ca 2+ entry and supported neurotransmitter release, but their effects on postsynaptic receptor levels were opposing, with combined loss rescuing postsynaptic function.