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Dopamine D1 receptors co-distribute with N-methyl-D-aspartic acid type-1 subunits and modulate synaptically-evoked N-methyl-D-aspartic acid currents in rat basolateral amygdala.
Neuroscience. 2006 Oct 27; 142(3):671-90.N

Abstract

Activation of dopamine D1 or glutamate, N-methyl-d-aspartic acid (NMDA) receptors in the basolateral amygdala (BLA) can potently influence affective behaviors and associative learning. Physical protein-protein interactions also can occur between C-terminal peptides of D1 receptors and the NMDA-receptor subunit-1 (NR1), suggesting intracellular associations of direct relevance to dopaminergic modulation of NMDA currents. We examined this possibility by combining electron microscopic immunolabeling of the D1 and NR1 C-terminal peptides with in vitro patch-clamp recording in the rat BLA. In the in vivo preparations, D1 and NR1 were localized to the surface or endomembranes of many of the same somata and dendrites as well as a few axon terminals, including those forming asymmetric, excitatory-type synapses. In vitro analysis of physiologically characterized projection neurons revealed an excitatory response to bath application of either dopamine or the preferential D1 receptor agonist, dihydrexidine. In these neurons, dopamine also selectively reduced stimulation-evoked isolated NMDA receptor-mediated currents, but not isolated non-NMDA receptor-mediated currents or the response to exogenous NMDA application. The selective reduction of the NMDA receptor-mediated currents suggests that this effect occurs at a postsynaptic locus. Moreover, both D1 and NR1 were localized to postsynaptic surfaces of biocytin-filled and physiologically characterized projection neurons. Our results provide ultrastructural evidence for D1/NR1 endomembrane associations that may dynamically contribute to the attenuation of NMDA receptor-mediated currents following prior activation of D1 receptors in BLA projection neurons. The potential for postsynaptic cross-talk between D1 and NMDA receptors in BLA projection neurons as well as a similar interaction in presynaptic terminals could have important implications for the formation and extinction of affective memories.

Authors+Show Affiliations

Department of Neurology and Neuroscience, Weill Medical College of Cornell University, 411 East 69th Street, Room KB-410, New York, NY 10021, USA. vpickel@med.cornell.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

16905271

Citation

Pickel, V M., et al. "Dopamine D1 Receptors Co-distribute With N-methyl-D-aspartic Acid Type-1 Subunits and Modulate Synaptically-evoked N-methyl-D-aspartic Acid Currents in Rat Basolateral Amygdala." Neuroscience, vol. 142, no. 3, 2006, pp. 671-90.
Pickel VM, Colago EE, Mania I, et al. Dopamine D1 receptors co-distribute with N-methyl-D-aspartic acid type-1 subunits and modulate synaptically-evoked N-methyl-D-aspartic acid currents in rat basolateral amygdala. Neuroscience. 2006;142(3):671-90.
Pickel, V. M., Colago, E. E., Mania, I., Molosh, A. I., & Rainnie, D. G. (2006). Dopamine D1 receptors co-distribute with N-methyl-D-aspartic acid type-1 subunits and modulate synaptically-evoked N-methyl-D-aspartic acid currents in rat basolateral amygdala. Neuroscience, 142(3), 671-90.
Pickel VM, et al. Dopamine D1 Receptors Co-distribute With N-methyl-D-aspartic Acid Type-1 Subunits and Modulate Synaptically-evoked N-methyl-D-aspartic Acid Currents in Rat Basolateral Amygdala. Neuroscience. 2006 Oct 27;142(3):671-90. PubMed PMID: 16905271.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dopamine D1 receptors co-distribute with N-methyl-D-aspartic acid type-1 subunits and modulate synaptically-evoked N-methyl-D-aspartic acid currents in rat basolateral amygdala. AU - Pickel,V M, AU - Colago,E E, AU - Mania,I, AU - Molosh,A I, AU - Rainnie,D G, Y1 - 2006/08/14/ PY - 2006/02/24/received PY - 2006/06/28/revised PY - 2006/06/30/accepted PY - 2006/8/15/pubmed PY - 2007/1/4/medline PY - 2006/8/15/entrez SP - 671 EP - 90 JF - Neuroscience JO - Neuroscience VL - 142 IS - 3 N2 - Activation of dopamine D1 or glutamate, N-methyl-d-aspartic acid (NMDA) receptors in the basolateral amygdala (BLA) can potently influence affective behaviors and associative learning. Physical protein-protein interactions also can occur between C-terminal peptides of D1 receptors and the NMDA-receptor subunit-1 (NR1), suggesting intracellular associations of direct relevance to dopaminergic modulation of NMDA currents. We examined this possibility by combining electron microscopic immunolabeling of the D1 and NR1 C-terminal peptides with in vitro patch-clamp recording in the rat BLA. In the in vivo preparations, D1 and NR1 were localized to the surface or endomembranes of many of the same somata and dendrites as well as a few axon terminals, including those forming asymmetric, excitatory-type synapses. In vitro analysis of physiologically characterized projection neurons revealed an excitatory response to bath application of either dopamine or the preferential D1 receptor agonist, dihydrexidine. In these neurons, dopamine also selectively reduced stimulation-evoked isolated NMDA receptor-mediated currents, but not isolated non-NMDA receptor-mediated currents or the response to exogenous NMDA application. The selective reduction of the NMDA receptor-mediated currents suggests that this effect occurs at a postsynaptic locus. Moreover, both D1 and NR1 were localized to postsynaptic surfaces of biocytin-filled and physiologically characterized projection neurons. Our results provide ultrastructural evidence for D1/NR1 endomembrane associations that may dynamically contribute to the attenuation of NMDA receptor-mediated currents following prior activation of D1 receptors in BLA projection neurons. The potential for postsynaptic cross-talk between D1 and NMDA receptors in BLA projection neurons as well as a similar interaction in presynaptic terminals could have important implications for the formation and extinction of affective memories. SN - 0306-4522 UR - https://www.unboundmedicine.com/medline/citation/16905271/Dopamine_D1_receptors_co_distribute_with_N_methyl_D_aspartic_acid_type_1_subunits_and_modulate_synaptically_evoked_N_methyl_D_aspartic_acid_currents_in_rat_basolateral_amygdala_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(06)00928-6 DB - PRIME DP - Unbound Medicine ER -