title: Distribution of IP3-mediated calcium responses and their role in nuclear signalling in rat basolateral amygdala neurons.
abstract: 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.
authors.affiliation: Queensland Brain Institute, The University of Queensland, St Lucia, Queensland 4072, Australia.
authors.forename: John M
authors.initials: JM
authors.lastname: Power
authors.forename: Pankaj
authors.initials: P
authors.lastname: Sah
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000679:Amygdala / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D003712:Dendrites / Q000378:metabolism; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014018:Tissue Distribution
chemical_list: D018094:Receptors, Metabotropic Glutamate; D011976:Receptors, Muscarinic; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium