Synaptic crosstalk conferred by a zone of differentially regulated Ca2+ signaling in the dendritic shaft adjoining a potentiated spine.

Patterns of postsynaptic activity that induce long-term potentiation of fast excitatory transmission at glutamatergic synapses between hippocampal neurons cause enlargement of the dendritic spine and promote growth in spine endoplasmic reticulum (ER) content. Such postsynaptic activity patterns also impact Ca2+ signaling in the adjoining dendritic shaft, in a zone centered on the spine-shaft junction and extending ∼10-20 µm in either direction along the shaft. Comparing this specialized zone in the shaft with the dendrite in general, plasticity-inducing stimulation of a single spine causes more profound depletion of Ca2+ stores in the ER, a greater degree of interaction between stromal interaction molecule 1 (STIM1) and L-type Ca2+ channels, and thus stronger STIM1 inhibition of these channels. Here we show that the length of this zone along the dendritic axis can be approximately doubled through the neuromodulatory action of β-adrenergic receptors (βARs). The mechanism of βAR enlargement of the zone arises from protein kinase A-mediated enhancement of L-type Ca2+ current, which in turn lowers [Ca2+]ER through ryanodine receptor-dependent Ca2+-induced Ca2+ release and activates STIM1 feedback inhibition of L-type Ca2+ channels. An important function of this dendritic zone is to support crosstalk between spines along its length such that spines neighboring a strongly stimulated spine are enabled to undergo structural plasticity in response to stimulation that would otherwise be subthreshold for spine structural plasticity. This form of crosstalk requires L-type Ca2+ channel current to activate STIM1, and βAR activity extends the range along the shaft over which such spine-to-spine communication can occur.