期刊
EXPERIMENTAL NEUROLOGY
卷 227, 期 1, 页码 149-158出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2010.10.010
关键词
Addiction; Glutamate; Opioids; Synaptic plasticity
资金
- [DA-027128]
- [DA-024030]
- NATIONAL INSTITUTE ON DRUG ABUSE [R03DA027128, R01DA024030] Funding Source: NIH RePORTER
Activation of GluR2-expressing non-calcium-permeable AMPA-type glutamate receptors in the central nucleus of the amygdala (CeA) may play an important role in integrating emotion and memory with goal-directed behaviors involved in opioid addiction. The location of non-calcium-permeable AMPA receptors within distinct neuronal compartments (i.e., soma, dendrite, or axon) is an important functional feature of these proteins; however, their ultrastructural location and subcellular relationship with mu-opioid receptors (mu OR) in the CeA are unknown. Immunocytochemical electron microscopy was used to characterize the ultrastructural distribution of GluR2 and its association with mu OR in the mouse CeA. A single-labeling analysis of GluR2 distribution employing immunoperoxidase or immunogold markers revealed that this protein was frequently affiliated with intracellular vesicular organelles, as well as the plasma membrane of CeA neuronal profiles. Among all GluR2-labeled neuronal structures, over 85% were dendrites or somata. Unlabeled axon terminals frequently formed asymmetric excitatory-type synaptic junctions with GluR2-labeled dendritic profiles. Dual-labeling immunocytochemical analysis showed that GluR2 and mu OR were co-localized in neuronal compartments. Among all dual-labeled structures, approximately 80% were dendritic. Synaptic inputs to these dual-labeled dendrites were frequently from unlabeled axon terminals forming asymmetric excitatory-type synapses. The presence of GluR2 in dendritic profiles receiving asymmetric synapses suggests that activation of the non-calcium-permeable AMPA receptor plays a role in the postsynaptic modulation of excitatory signaling involving CeA neuronal circuits that coordinate sensory, affective, and behavioral processes involved in drug addiction. Given the critical role of non-calcium-permeable AMPA receptor function in neural and behavioral adaptability, their dendritic association with mu OR in CeA dendrites provides a neuronal substrate for opioid-mediated plasticity. (C) 2010 Elsevier Inc. All rights reserved.
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