Seminaires externes en novembre du 04/11/2013 au 25/11/2013

Lundi 4 novembre
CLAUDE COLOMER

Action potential regulation of Arc expression

Erasmus MC, Rotterdam

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 showedthat nanostimulation-induced Arc expression required APs 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

Mardi 12 novembre

ISMAEL VALLADOLID ACEBES

Vulnerability to mood disorders linked to diet-induced diabesity is dependent on SNAP-25b expression

Karolinska Institute, Stockholm

In the last two decades, there has been a dramatic increase in the prevalence of obesity, type-2 diabetes and associated complications (diabesity). Epidemiological data suggest that diabesity is also linked to an increased risk of depression and mood disorders as well as cognitive impairment. However, there is currently little information about the biological mechanisms that link the development of depression and/or cognitive dysfunctions to metabolic disorders. Synaptic transmission and plasticity are intimately associated with the regulated release of neurotransmitters, mediated by similar molecular machineries releasing hormones and neuropeptides from a wide variety of excitable cells. Thus, alterations of hormonal release profiles coupled to metabolic dysfunction might be accompanied by changes in neuroexocytosis resulting in synaptic impairment, identifying the control of regulated membrane fusion as a common and possibly susceptible link for diet-induced damages both in periphery and in brain. HYPOTHESIS: Individuals with a genetic predisposal for a derangement of the machinery controlling release of neurotransmitters, neuropeptides and hormones have an increased vulnerability to develop mood disorders linked to diet-induced diabesity. AIMS: To further investigate the possible association between impairment in regulated exocytosis and diet-induced damages in peripheral tissue and brain, we performed “Western Diet” interventions in wild-type C57BL/6 and SNAP-25b deficient mice. METHODS: We monitored body weight, food intake and body fat distribution, as well as performed behavioural experiments. Glucose and lipid homeostasis characterization has been performed by using in vivo and in vitro studies. Examination of brain and peripheral tissues by using Western immunoblotting allowed to us to analyse the expression of proteins involved on leptin and/or insulin signalling pathways. RESULTS AND CONCLUSIONS: Our major findings deal with the higher vulnerability to dietinduced diabesity detected in SNAP-25b null mice. These peripheral complications occur concomitantly with depressive-like behaviour and motor dysfunctions, suggesting that an intact release of transmitters, neuropeptides and/or hormones by SNAP-25b is essential for prevention of major metabolic abnormalities related to eating behaviour, as well as to the onset of motor dysfunctions and depressive-like behaviour.

Lundi 18 novembre

VERONICA ALVAREZ

A synaptic mechanism controlling motivated behavior and compulsive cocaine use

NIH, Besthesda

Addiction is characterized by a loss of control in drug intake, which is seen only in a fraction of those exposed to stimulant drugs like cocaine. Low levels of D2 receptors in the striatum have been linked to the vulnerability to develop compulsive drug use; however, cellular or synaptic mechanisms associated with a resistant to develop the behavior are unknown. Here we show that individual variability in the development of high motivation and perseverative behavior toward cocaine is associated with synaptic plasticity in medium spiny neurons expressing dopamine D2 receptors (D2-MSNs) in the nucleus accumbens. Potentiation of glutamatergic inputs onto indirect pathway D2-MSNs was a hallmark of animals that resisted compulsive cocaine use. Furthermore, inhibition of D2-MSNs enhanced the motivation to obtain cocaine. These results indicate that recruitment of D2-MSNs in nucleus accumbens functions to restrain cocaine self-administration and serves as a natural protective mechanism in some individuals.

Lundi 25 novembre

LAURENT NGUYEN

Molecular regulation of neuronal migration in the developing cerebral cortex

Universite de Liège, Liège

The complex organization of the cerebral cortex reflects the elaborated patterns of cell migration that contributed to its development. The cortex contains neurons that are distributed within layers and are regionally organized into specialized areas that underlie sophisticated motor, cognitive and perceptual abilities. Cortical lamination follows a sequence of neuronal placement and maturation that arises from the successive birth and orderly migration of two major classes of neurons, the projection neurons and the interneurons. These neurons use distinct migration behaviours to reach and settle into the developing cortex and recent studies suggest that defects in neuronal migration lead to several disorders, which, in human, are characterised, by learning disabilities, mental retardation or epilepsy. Defining how cortical neurons migrate and integrate into specific cortical neuronal networks is therefore essential for understanding the biological basis of these disorders. My talk will give an overview of our recent work deciphering novel molecular mechanisms that drive neuronal migration in the cerebral cortex.