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¹ Queensland Brain Institute, University of Queensland, St Lucia, Queensland 4072, Australia

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 Ca²⁺ in the dendrites that propagate as waves into the soma and nucleus. These Ca²⁺ waves initiate in the proximal dendrites and show limited propagation centrifugally away from the soma. In other cell types, Ca²⁺ 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 Ca²⁺ from inositol 1,4,5-trisphosphate (IP₃)-sensitive intracellular Ca²⁺ stores. Whereas action potentials (APs) alone were relatively ineffective in raising nuclear Ca²⁺, their pairing with metabotropic receptor activation evoked an IP₃-receptor-mediated Ca²⁺-induced Ca²⁺ release, raising nuclear Ca²⁺ into the micromolar range. Metabotropic-receptor-mediated Ca²⁺-store release was highly compartmentalized. When coupled with metabotropic receptor stimulation, large robust Ca²⁺ 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 Ca²⁺ transient was detected in spine-dense high-order dendritic segments. Ca²⁺ rises evoked by photolytic uncaging of IP₃ showed the same distribution, suggesting that IP₃-sensitive Ca²⁺ 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.

(Received 19 November 2006; accepted after revision 9 February 2007; first published online 15 February 2007)
Corresponding author P. Sah: Queensland Brain Institute, The University of Queensland, St Lucia, Queensland 4072, Australia. Email: pankaj.sah{at}uq.edu.au

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