Dataset Information

Morphine-Associated Contextual Cues Induce Structural Plasticity in Hippocampal CA1 Pyramidal Neurons.

ABSTRACT: In people with a prior history of opioid misuse, cues associated with previous drug intake can trigger relapse even after years of abstinence. Examining the processes that lead to the formation and maintenance of the memories between cues/context and the opioid may help to discover new therapeutic candidates to treat drug-seeking behavior. The hippocampus is a brain region essential for learning and memory, which has been involved in the mechanisms underlying opioid cravings. The formation of memories and associations are thought to be dependent on synaptic strengthening associated with structural plasticity of dendritic spines. Here, we assess how dendritic spines in the CA1 region of the hippocampus are affected by morphine-conditioning training. Our results show that morphine pairing with environmental cues (ie, the conditioned place preference (CPP) apparatus) triggers a significant decrease in the number of thin dendritic spines in the hippocampus. Interestingly, this effect was observed regardless of the expression of a conditioned response when mice were trained using an unpaired morphine CPP design and was absent when morphine was administered in the home cage. To investigate the mechanism underlying this structural plasticity, we examined the role of Rho GTPase in dendritic spine remodeling. We found that synaptic expression of RhoA increased with morphine conditioning and blocking RhoA signaling prevented the expression of morphine-induced CPP. Our findings uncover novel mechanisms in response to morphine-associated environmental cues and the underlying alterations in spine plasticity.

SUBMITTER: Fakira AK

PROVIDER: S-EPMC5026734 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Morphine-Associated Contextual Cues Induce Structural Plasticity in Hippocampal CA1 Pyramidal Neurons.

Fakira Amanda K AK Massaly Nicolas N Cohensedgh Omid O Berman Alexandra A Morón Jose A JA

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20160510 11

In people with a prior history of opioid misuse, cues associated with previous drug intake can trigger relapse even after years of abstinence. Examining the processes that lead to the formation and maintenance of the memories between cues/context and the opioid may help to discover new therapeutic candidates to treat drug-seeking behavior. The hippocampus is a brain region essential for learning and memory, which has been involved in the mechanisms underlying opioid cravings. The formation of me ...[more]

PMID: 27170097

Similar Datasets

Project description:BackgroundHippocampal CA1 pyramidal neurons receive two excitatory glutamatergic synaptic inputs: their most distal dendritic regions in the stratum lacunosum-moleculare (SLM) are innervated by the perforant path (PP), originating from layer III of the entorhinal cortex, while their more proximal regions of the apical dendrites in the stratum radiatum (SR) are innervated by the Schaffer-collaterals (SC), originating from hippocampal CA3 neurons. Endocannabinoids (eCBs) are naturally occurring mediators capable of modulating both GABAergic and glutamatergic synaptic transmission and plasticity via the CB1 receptor. Previous work on eCB modulation of excitatory synapses in the CA1 region largely focuses on the SC pathway. However, little information is available on whether and how eCBs modulate glutamatergic synaptic transmission and plasticity at PP synapses.Methodology/principal findingsBy employing somatic and dendritic patch-clamp recordings, Ca(2+) uncaging, and immunostaining, we demonstrate that there are significant differences in low-frequency stimulation (LFS)- or DHPG-, an agonist of group I metabotropic glutamate receptors (mGluRs), induced long-term depression (LTD) of excitatory synaptic transmission between SC and PP synapses in the same pyramidal neurons. These differences are eliminated by pharmacological inhibition with selective CB1 receptor antagonists or genetic deletion of the CB1 receptor, indicating that these differences likely result from differential modulation via a CB1 receptor-dependent mechanism. We also revealed that depolarization-induced suppression of excitation (DSE), a form of short-term synaptic plasticity, and photolysis of caged Ca(2+)-induced suppression of Excitatory postsynaptic currents (EPSCs) were less at the PP than that at the SC. In addition, application of WIN55212 (WIN) induced a more pronounced inhibition of EPSCs at the SC when compared to that at the PP.Conclusions/significanceOur results suggest that CB1 dependent LTD and DSE are differentially expressed at the PP versus SC synapses in the same neurons, which may have an impact on synaptic scaling, integration and plasticity of hippocampal CA1 pyramidal neurons.

Dataset Information

Morphine-Associated Contextual Cues Induce Structural Plasticity in Hippocampal CA1 Pyramidal Neurons.

Publications

Morphine-Associated Contextual Cues Induce Structural Plasticity in Hippocampal CA1 Pyramidal Neurons.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets