ORCID Profile
0000-0002-5754-8873
Current Organisation
Sorbonne University
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Publisher: Springer Science and Business Media LLC
Date: 08-07-2014
DOI: 10.1007/S00429-014-0837-2
Abstract: Addiction can be considered as a form of neuronal adaptation within the reward circuitry. Upon psychostimulant administration, long-term behavioral adaptations are associated with synaptic plasticity and morphological changes of medium spiny neurons (MSN) from the striatum. Increased spine density onto MSN in response to chronic cocaine exposure in mice has been described for more than a decade, but no evidence indicates that these newly formed spines establish connections. We developed a method for labeling, automated detection and morphological analysis of synaptic contacts. In idual labeling of neurons in mice that express the Vesicular GLUtamate Transporter-1 fused to Venus allows visualization of both dendritic spines and axonal boutons. Automated three-dimensional segmentation and morphometric analysis retrieve information on thousands of synapses at high resolution. We used this method to demonstrate that new cortico-striatal connections are formed in the striatum upon chronic cocaine. We also show that the cortical input weight is preserved over other cerebral inputs and that the newly formed spines contact pre-existing axonal boutons. Our results pave the way for other studies, since our method can be applied to any other neuronal type as demonstrated herein for glutamatergic connections on pyramidal neurons and Purkinje cells.
Publisher: Elsevier BV
Date: 02-2017
DOI: 10.1016/J.YMETH.2016.11.016
Abstract: We present a new plugin for ImageJ called DiAna, for Distance Analysis, which comes with a user-friendly interface. DiAna proposes robust and accurate 3D segmentation for object extraction. The plugin performs automated object-based co-localization and distance analysis. DiAna offers an in-depth analysis of co-localization between objects and retrieves 3D measurements including co-localizing volumes and surfaces of contact. It also computes the distribution of distances between objects in 3D. With DiAna, we furthermore introduce an original method, which allows for estimating the statistical significance of object co-localization. DiAna offers a complete and intuitive 3D image analysis tool for biologists.
Publisher: Elsevier BV
Date: 12-2017
DOI: 10.1016/J.BIOPSYCH.2017.03.014
Abstract: 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. 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. 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. 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.
No related grants have been discovered for nicolas heck.