Metabotropic receptor activation is important for learning, memory and synaptic plasticity in the amygdala and other brain regions. Synaptic stimulation of metabotropic receptors in basolateral amygdala (BLA) projection neurons evokes a focal rise in free Ca(2+) in the dendrites that propagate as waves into the soma and nucleus. These Ca(2+) waves initiate in the proximal dendrites and show limited propagation centrifugally away from the soma. In other cell types, Ca(2+) waves have been shown to be mediated by either metabotropic glutamate receptor (mGluR) or muscarinic receptor (mAChR) activation. Here we show that mGluRs and mAChRs act cooperatively to release Ca(2+) from inositol 1,4,5-trisphosphate (IP(3))-sensitive intracellular Ca(2+) stores. Whereas action potentials (APs) alone were relatively ineffective in raising nuclear Ca(2+), their pairing with metabotropic receptor activation evoked an IP(3)-receptor-mediated Ca(2+)-induced Ca(2+) release, raising nuclear Ca(2+) into the micromolar range. Metabotropic-receptor-mediated Ca(2+)-store release was highly compartmentalized. When coupled with metabotropic receptor stimulation, large robust Ca(2+) rises and AP-induced amplification were observed in the soma, nucleus and sparsely spiny dendritic segments with metabotropic stimulation. In contrast, no significant amplification of the Ca(2+) transient was detected in spine-dense high-order dendritic segments. Ca(2+) rises evoked by photolytic uncaging of IP(3) showed the same distribution, suggesting that IP(3)-sensitive Ca(2+) stores are preferentially located in the soma and proximal dendrites. This distribution of metabotropic-mediated store release suggests that the neuromodulatory role of metabotropic receptor stimulation in BLA-dependent learning may result from enhanced nuclear signalling.