Marc Dos Santos1, Marine Salery1, Benoit Forget1, Maria Alexandra Garcia Perez1, Sandrine Betuing1, Thomas Boudier2, Peter Vanhoutte1, Jocelyne Caboche3, Nicolas Heck1. 1. Neurosciences Paris Seine, Institut de Biologie Paris Seine, University Pierre and Marie Curie University of Paris 06, Sorbonne Universités, Centre National pour la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Paris, France. 2. Neurosciences Paris Seine, Institut de Biologie Paris Seine, University Pierre and Marie Curie University of Paris 06, Sorbonne Universités, Centre National pour la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Paris, France; Bioinformatics Institute, Agency for Science, Technology, and Research, Singapore. 3. Neurosciences Paris Seine, Institut de Biologie Paris Seine, University Pierre and Marie Curie University of Paris 06, Sorbonne Universités, Centre National pour la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Paris, France. Electronic address: jocelyne.caboche@upmc.fr.
Abstract
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.
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.
Authors: Junshi Wang; King-Lun Li; Avani Shukla; Ania Beroun; Masago Ishikawa; Xiaojie Huang; Yao Wang; Yao Q Wang; Yue Yang; Noah D Bastola; Hugh H Huang; Lily E Kramer; Terry Chao; Yanhua H Huang; Susan R Sesack; Eric J Nestler; Oliver M Schlüter; Yan Dong Journal: Biol Psychiatry Date: 2020-08-25 Impact factor: 13.382
Authors: Benoit Forget; Jocelyne Caboche; Elena Martin Garcia; Arthur Godino; Laura Domingo Rodriguez; Vincent Kappes; Pierre Poirier; Andry Andrianarivelo; Eric Senabre Marchan; Marie-Charlotte Allichon; Mélanie Marias; Peter Vanhoutte; Jean-Antoine Girault; Rafael Maldonado Journal: Mol Psychiatry Date: 2021-11-16 Impact factor: 13.437
Authors: Marie-Charlotte Allichon; Vanesa Ortiz; Paula Pousinha; Andry Andrianarivelo; Anna Petitbon; Nicolas Heck; Pierre Trifilieff; Jacques Barik; Peter Vanhoutte Journal: Front Synaptic Neurosci Date: 2021-12-14