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Séminaire - Claude ColomerAction Potential Regulation of Arc Expression

Abstract :

The immediate-early gene Arc plays a key role in neuronal plasticity mechanisms underlying learning and memory. However, the exact relationship between neuronal activity and Arc expression has remained elusive. Here we used juxtacellular nanostimulation (Houweling & Brecht, 2008) to establish the relationship between action potential (AP) firing and Arc expression in single cortical pyramidal neurons in vivo.

We systematically varied the number and frequency of APs in single layer 2 pyramidal cells in barrel somatosensory cortex of Arc-dVenus transgenic mice and subsequently monitored fluorescence of the Arc reporter using confocal microscopy. Fluorescence was observed after firing as few as 25-200 APs depending on the rate of AP firing. For a given firing rate expression increased monotonically with increasing AP numbers and approached asymptotic levels after 500 APs. The relationship between neuronal activity and Arc expression displayed a strong AP frequency dependence such that spike trains at lower firing rates required larger numbers of APs to induce Arc expression and resulted in lower asymptotic levels. Control experiments showed that nanostimulation-induced Arc expression required action potentials and was not dependent on excitatory synaptic inputs. Additional experiments in which brief nanostimulation trials were applied at regular time intervals suggest that AP activity can be faithfully integrated over periods of time lasting up to tens of minutes.

Together, we demonstrate that Arc expression is tightly regulated by neuronal activity over a wide range of time scales, from seconds to minutes. Moreover, these results are the first to establish a quantitative transfer function between in vivo neuronal activity and gene expression, at the single cell level.

Selected publications

2012: Colomer C., Martin A.O., Desarménien M.G., Guérineau N.C. Gap junction-mediated intercellular communication in the adrenal medulla: An additional ingredient of stimulus-secretion coupling regulation. Biochim Biophys Acta., 1818(8):1937-51.

2010: Colomer C.*, Olivos Oré L.A.*, et al. Functional characterization of alpha9-containing cholinergic nicotinic receptors in the rat adrenal medulla: implication in stress-induced functional plasticity. J. Neurosci., 30(19):6732-42.

2009: Colomer C., Desarménien M.G., Guérineau N.C. Revisiting the stimulus-secretion coupling in the adrenal medulla: role of gap junction-mediated intercellular communication. Mol Neurobiol., 40(1): 87-100. review

2008: 1_Colomer C., et al. Functional remodeling of gap junction-mediated electrical communication between adrenal chromaffin cells in stressed rats. J. Neurosci. 28(26): 6616-26.

2_ Colomer C., Lafont C., Guérineau N.C. Stress-induced intercellular communication remodeling in the rat adrenal medulla. Ann. N. Y. Acad. Sci., 1148: 106-11.

2005: Colomer C.*, Ster J.*, et al. Insulin-like growth factor-1 inhibits adult supraoptic neurons via complementary modulation of mechanoreceptors and glycine receptors. J Neurosci. 25(9): 2267-76.

 

Christophe Mulle (mulle @ u-bordeaux2.fr)

Address...

Erasmus MC Department of Neuroscience
Research group(s): Houweling
Position: Post-doc
Visiting address: NL-3015 GE Rotterdam