Ultrastructural relationship between N-methyl-d-aspartate-NR1 receptor subunit and mu-opioid receptor in the mouse central nucleus of the amygdala

Abstract

The central nucleus of the amygdala (CeA) is an important neuroanatomical substrate of emotional processes that are critically involved in addictive behaviors. Glutamate and opioid systems in the CeA play significant roles in neural plasticity and addictive processes, however the cellular sites of interaction between agonists of N-methyl-d-aspar-tate (NMDA) and μ-opioid receptors (μOR) in the CeA are unknown. Dual labeling immunocytochemistry was used to determine the ultrastructural relationship between the essential NMDA-NR1 receptor subunit and μOR in the CeA. It was found that over 80% of NR1-labeled profiles were dendrites while less than 10% were axons. In the case of μOR-labeled profiles, approximately 60% were dendritic, and over 35% were axons. Despite their somewhat distinctive patterns of cellular location, numerous dual-labeled profiles were observed. Approximately 80% of these were dendritic, and less than 10% were axonal. Moreover, many dual-labeled dendritic profiles were contacted by axon terminals receiving asymmetric-type synapses indicative of excitatory signaling. These results indicate that NMDA and μORs are strategically localized in dendrites, including those receiving excitatory synapses, of central amygdala neurons. Thus, postsynaptic co-modulation of central amygdala neurons may be a key cellular substrate mediating glutamate and opioid interaction on neural signaling and plasticity associated with normal and pathological emotional processes associated with addictive behaviors.

Unraveling glutamate–opioid receptor interactions using high-resolution electron microscopy: Implications for addiction-related processes

“…Techniques used to discern the cellular distribution of glutamate and opioid receptor/ligand constituents have provided critical information pertaining to functional implications of interactions between these systems (Glass, et al, 2009). Using immunohistochemistry combined with electron microscopy, such high-resolution neuroanatomical studies have revealed sites of receptor interaction that can inform experimental approaches using pharmacological manipulation to target these systems under conditions of chronic use of abused substances versus control conditions.…”

The Mu-Opioid Receptor and the NMDA Receptor Associate in PAG Neurons: Implications in Pain Control

“…Importantly, these two receptors colocalize on single neurons within the CNS (reviewed by Trujillo, 2002), and at the ultrastructural level both receptors show convincing colocalization (Glass et al, 2009). Specifically, the midbrain periaqueductal gray (PAG) is densely innervated by glutamatergic projections from the forebrain, and there is robust MOR-NMDAR colocalization in the dendrites and somata of ventrolateral PAG neurons (Commons et al, 1999;Narita et al, 2008).…”

The histidine triad nucleotide-binding protein 1 supports mu-opioid receptor–glutamate NMDA receptor cross-regulation

“…In one such midbrain structure, the periaqueductal gray matter (PAG), the MOR are located superficially in the ventrolateral PAG and thus, they are accessible from the CSF [21]. At the ultrastructural level, MOR and NMDAR co-localize convincingly [22]. Specifically, the mesencephalic PAG is densely innervated by glutamatergic projections from the forebrain and these receptors co-localize robustly in the dendrites and somata of ventrolateral PAG neurons [10,23].…”