Activation of silent and weak synapses by cAMP‐dependent protein kinase in cultured cerebellar granule neurons

Non‐technical summary  It is accepted that learning involves creating or increasing the activity of existing chemical connections (synapses) between neurons. Some connections, known as ‘silent synapses’, have no detectable activity under resting conditions but can be switched on by electrical stimuli that mimic learning. To better understand how this occurs, we compared silent and active synapses in cultured neurons. When neurons were challenged with electrical stimulation, the extent of activation of previously active synapses was unchanged, whereas silent synapses were activated. Silent synapse activation did not correlate with increases in intracellular calcium (which evokes neurotransmitter release), but was dependent on the action of the enzyme protein kinase A. A large proportion of synapses in the adult brain are thought to be silent, and therefore a detailed knowledge of silent synapse activation could give insights into the mechanisms of learning and memory.