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© Research
Publication : Biological Psychiatry

Rapid Synaptogenesis in the Nucleus Accumbens Is Induced by a Single Cocaine Administration and Stabilized by Mitogen-Activated Protein Kinase Interacting Kinase-1 Activity.

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Biological Psychiatry - 14 Mar 2017

Dos Santos M, Salery M, Forget B, Garcia Perez MA, Betuing S, Boudier T, Vanhoutte P, Caboche J, Heck N.

Link to Pubmed [PMID] – 28545678

Biol Psychiatry. 2017 Dec 1;82(11):806-818. doi: 10.1016/j.biopsych.2017.03.014. Epub 2017 Mar 29

BACKGROUND:

Repeated cocaine exposure produces new spine formation in striatal projection neurons (SPNs) of the nucleus accumbens. However, an acute exposure to cocaine can trigger long-lasting synaptic plasticity in SPNs leading to behavioral alterations. This raises the intriguing question as to whether a single administration of cocaine could enduringly modify striatal connectivity.

METHODS:

A three-dimensional morphometric analysis of presynaptic glutamatergic boutons and dendritic spines was performed on SPNs 1 hour and 1 week after a single cocaine administration. Time-lapse two-photon microscopy in adult slices was used to determine the precise molecular-events sequence responsible for the rapid spine formation.

RESULTS:

A single injection triggered a rapid synaptogenesis and persistent increase in glutamatergic connectivity in SPNs from the shell part of the nucleus accumbens, specifically. Synapse formation occurred through clustered growth of active spines contacting pre-existing axonal boutons. Spine growth required extracellular signal-regulated kinase activation, while spine stabilization involved transcription-independent protein synthesis driven by mitogen-activated protein kinase interacting kinase-1, downstream from extracellular signal-regulated kinase. The maintenance of new spines driven by mitogen-activated protein kinase interacting kinase-1 was essential for long-term connectivity changes induced by cocaine in vivo.

CONCLUSIONS:

Our study originally demonstrates that a single administration of cocaine is able to induce stable synaptic rewiring in the nucleus accumbens, which will likely influence responses to subsequent drug exposure. It also unravels a new functional role for cocaine-induced extracellular signal-regulated kinase pathway independently of nuclear targets. Finally, it reveals that mitogen-activated protein kinase interacting kinase-1 has a pivotal role in cocaine-induced connectivity.

https://www.ncbi.nlm.nih.gov/pubmed/28545678