Memory retrieval in addiction: a role for miR-105-mediated regulation of D1 receptors in mPFC neurons projecting to the basolateral amygdala

Abstract

BackgroundDrug addiction is a chronic brain disorder characterized by the compulsive use of drugs. The study of chronic morphine-induced adaptation in the brain and its functional significance is of importance to understand the mechanism of morphine addiction. Previous studies have found a number of chronic morphine-induced adaptive changes at molecular levels in the brain. A study from our lab showed that chronic morphine-induced increases in the expression of D1 receptors at presynaptic terminals coming from other structures to the basolateral amygdala (BLA) played an important role in environmental cue-induced retrieval of morphine withdrawal memory. However, the neurocircuitry where the increased D1 receptors are located and how chronic morphine increases D1 receptor expression in specific neurocircuits remain to be elucidated.ResultsOur results show that chronic morphine induces a persistent increase in D1 receptor expression in glutamatergic terminals of projection neurons from the medial prefrontal cortex (mPFC) to the BLA, but has no influence on D1 receptor expression in projection neurons from the hippocampus or the thalamus to the BLA. This adaptation to chronic morphine is mediated by reduced expression of miR-105 in the mPFC, which results in enhanced D1 receptor expression in glutamatergic terminals of projection neurons from the mPFC to the BLA. Ex vivo optogenetic experiments show that a chronic morphine-induced increase in D1 receptor expression in glutamatergic terminals of projection neurons from the mPFC to the BLA results in sensitization of the effect of D1 receptor agonist on presynaptic glutamate release. mPFC to BLA projection neurons are activated by withdrawal-associated environmental cues in morphine-withdrawal rats, and overexpression of miR-105 in the mPFC leads to reduced D1 receptor induction in response to chronic morphine in glutamatergic terminals of the projection neurons from the mPFC to the BLA, and a reduction in place aversion conditioned by morphine withdrawal.ConclusionsThese results suggest that chronic morphine use induces a persistent increase in D1 receptors in glutamatergic terminals of projection neurons from the mPFC to the BLA via downregulation of miR-105 in the mPFC, and that these adaptive changes contribute to environmental cue-induced retrieval of morphine withdrawal memory.Electronic supplementary materialThe online version of this article (doi:10.1186/s12915-017-0467-2) contains supplementary material, which is available to authorized users.

Deep sequencing of small non-coding RNA highlights brain-specific expression patterns and RNA cleavage

“…Only three high-confidence susscrofa miRNA, mir-105, mir-124a, mir-1264, were exclusively expressed in all three brain regions, but not in the adrenal gland. This resonates well with previous studies on mammalian tissue-specific miRNA expression, as brain-enriched mir-124 is well conserved from worms to humans and is estimated to be the most abundant miRNA in the brain [33]; Mir-105 as well as mir-1264 have been implicated in brain-specific functions [30,34].…”

Cell-type specific D1 dopamine receptor modulation of projection neurons and interneurons in the prefrontal cortex

“…Alternatively, D1-R expression may fluctuate within the IT cell-class, either over the course of development, in response to activity, or salient stimuli (Brenhouse HC et al 2008;Zhao Y et al 2017). In the future, it will be interesting to assess the functional significance of individual IT neuron sub-classes within PFC, and determine the importance of dopamine modulation on these diverse populations of projection neurons (Otsuka T and Y Kawaguchi 2011;Hirai Y et al 2012;Ueta Y et al 2013;Yamashita T et al 2013).…”

Early Life Stress and the Onset of Obesity: Proof of MicroRNAs’ Involvement Through Modulation of Serotonin and Dopamine Systems’ Homeostasis

“…Increased evidence points out that several components of the dopaminergic system are influenced by some miRNAs ( Table 2 ). DRD1 appears to be regulated by miR-504 ( Zhang et al, 2013 ), rno-miR-105 ( Zhao et al, 2017 ), and for the cluster of hsa-miR-15a-5p, hsa-miR-15b-5p, and hsa-miR-16-5p, and mmu-miR-142-3p ( Tobón et al, 2012 , 2015 ). The expression of the DRD2 is modified by miR-143-3p ( Wang et al, 2019 ), miR-200a ( Wu et al, 2018 ), miR-504 ( Zhang et al, 2013 ), hsa-miR-9, and hsa-miR-326 ( Shi et al, 2014 ; Zhang et al, 2015 ; Gangisetty et al, 2017 ; Mavrikaki et al, 2019 ).…”