CC BY
14
Section CELLULAR NEUROSCIENCE
VMAT2 in Astrocytes Regulates Morphology of Pyramidal Neurons in Developing Pfc by Modulating Extracellular Levels of Dopamine
Pucci L.1 *, Tamara Z.1, Petrelli F.1, Cali C.1, Dellerac G.2, Kirchhoff F.3, Déglon N.4,5, Giros B.6,7,Edwards R.8, Mothet J.P.2, Paola Bezzi1
1 Department of Fundamental Neuroscience (DNF), University of Lausanne (UNIL), Lausanne, Switeerland;
2 Centre de Recherche en Neurobiologie et Neurophysiologie de Marseille, Aix-Marseille Université UMR7286 CNRS 13344 Marseille Cedex 15, France;
3 Department of Molecular Physiology, University of Saarland, D-66421 Homburg, Germany CMBN, Rikshospitale;
4 Department of Clinical Neurosciences, CHUV, University of Lausanne, Switeerland;
5 Neuroscience Research Center, CHUV, CH-1011 Lausanne, Switeerland;
6 Department of Psychiatry, Douglas Mental Health University Institute, McGill University, Montreal, Quebec, H4H1R3, Canada;
7 NSERM, UMRS 1130; CNRS, UMR 8246; Sorbonne University UPMC, Neuroscience Paris-Seine, F-75005, Paris, France CNRS;
8 Departments of Neurology and Physiology, University of California San Francisco, San Francisco, California 94158, USA. * Presenting e-mail: luca.pucci@unil.ch
OM&P
Neuromodulation of neuronal circuits of the prefrontal cortex (PFC) by monoamines influences synaptic plasticity and executive functions and may play critical roles in psychiatric disorders (Arnsten et al., Neuron., 2012). The cellular mechanisms governing the homeostasis of monoamines in the developing PFC are not completely defined. Evidence that astrocytes express the whole enzymatic apparatus for the metabolism of monoamines (Youdim et al., Nature Rev Neurosci., 2006) strongly suggests a possible involvement of astroglial cells in mechanisms governing monoaminergic homeostasis.
Here we report that astrocytes located in PFC express a plasma membrane organic cation transporters 3 (OCT-3) and contain dopamine (DA). Moreover we found that astrocytes express vesicular monoamine transporter 2 (VMAT2) and that the signal of this transporter was readily recognizable on different subset of intracellular organelles such as endosomes and lysosomes. The physiological relevance of VMAT2 in astrocytes is investigated by generating conditional transgenic mice in which VMAT2 is specifically deleted in GFAP expressing cells (aVMAT2cKO). Interestingly, VMAT2 deletion in astrocytes leads to a specific deficits in astrocytes storing DA and a decrease in the extracellular levels of DA in the PFC. Moreover, we found out that the decreased levels of DA in the developing PFC of aVMAT2cKO mice alters the spine formation of pyramidal neurons that can be rescued by chronic administration of L-DOPA or VMAT2 re-expression in astrocytes by lentivirus during postnatal development. These results highlight a critical role for VMAT2 in astrocytes in the regulation of DA levels and the normal development of pyramidal neurons in the PFC.
Unraveling the Role of Astroglial Networks in Neuronal Coordination
Nathalie Rouach*
College de France, France.
* Presenting e-mail: nathalie.rouach@college-de-france.fr
Astrocytes interact with neurons to regulate network activity. Although the gap junction subunits connexin 30 and connexin 43 mediate the formation of extensive astroglial networks that cover large functional neuronal territories, their role in neuronal synchronization remains unknown. Using connexin 30- and connexin 43-deficient mice, we showed that astroglial networks promoted sustained population bursts in hippocampal slices by setting the basal active state of neurons. Astroglial networks limited excessive neuronal depolarization induced by spontaneous synaptic activity, increased neuronal release probability, and favored the recruitment of neurons during bursting, thus promoting the coordinated activation of neuronal networks. In vivo, this sustained neuronal coordination translated into increased severity of acutely evoked epileptiform events and convulsive behavior. These results revealed that connexin-mediated astroglial networks synchronize bursting of neuronal assemblies, which can exacerbate pathological network activity and associated behavior.
Opera Med Physiol 2016 Vol. 2 (S1) 7
