Synaptic transmission; Glutamate receptors; Prenatal nicotine exposure; Dopamine; Midbrain system; Drugs of abuse; Development
Yuan Tifei, Mameli Manuel, O' Connor Eoin, Dey Partha, Verpelli Chiara, Sala Carlo, Perez-Otano Isabel, Lüscher Christian, Bellone Camilla (2013), Expression of cocaine-evoked synaptic plasticity by GluN3A-containing NMDA receptors., in Neuron
, 80(4), 1025.
Yuan Tifei, Bellone Camilla (2013), Glutamatergic receptors at developing synapses: the role of GluN3A-containing NMDA receptors and GluA2-lacking AMPA receptors., in European Journal Pharmacology
Paoletti Pierre, Bellone Camilla, Zhou Qiang (2013), NMDA receptor subunit diversity: impact on receptor properties, synaptic plasticity and disease., in Nat. Rev. Neurosci.
Bellone Camilla, Lüscher Christian (2012), Drug-evoked plasticity: do addictive drugs reopen a critical period of postnatal synaptic development?, in Front Mol Neurosci
Camilla Bellone, Manuel Mameli (2012), mGluR-Dependent Synaptic Plasticity in Drug-Seeking., in Front Pharmacol.
Bellone Camilla, Mameli Manuel, Lüscher Christian (2011), In utero exposure to cocaine delays postnatal synaptic maturation of glutamatergic transmission in the VTA., in Nature neuroscience
, 14(11), 1439-46.
De la Rossa andres, Bellone Camilla, Golding Bruno, Vitali Ilaria, Moss Jonathan, Toni Nicolas, Lüscher Christian, Jabaudon Denis, In vivo reprogramming of circuit connectivity in postmitotic neocortical neurons., in n vivo reprogramming of circuit connectivity in postmitotic neocortical neurons
, on line-doi:10.103.
Golding Bruno, Pouchelon Gabrielle, Bellone Camilla, Murthy Sahana, DiNardo Ariel, Govindan Subashoka, Luscher Christian, Shimogori Tomomi, Dayer Alexandre, Jabaudon Denis, Retinal Input Directs the Recruitment of Inhibitory Interneurons Into Thalamic Visual Circuits., in Neuron
O' Connor Eoin, Bariselli Sebastiano, Bellone Camilla, Synaptic Basis of Social Dysfunction: A focus on Postsynaptic Proteins Linking Group-I mGluRs with AMPARs and NMDARs, in EJN
Background: Nicotine from tobacco smoking is one of the most highly addictive substances and has a major social and health consequence. However tobacco exposure is not only a health concern for adults; it has been shown to exert deleterious effects on the health of the fetus, newborn and adolescent as well. Tobacco in fact is the most commonly used substance during pregnancy (up to 25% pregnant women smoke) and direct effects of nicotine predict neurobehavioral deficits in the offspring, which may have long-lasting effects on brain function and cognition. Animal models that mimic nicotine levels of pregnant women produce neurobehavioral effect in the offspring including changes in locomotors activity, reward system and cognition. Nicotine in fact crosses the placenta and interacts with nicotine acetylcholine receptors (nAChRs). This interaction physiologically regulates the catecholamine function in the central nervous system (CNS), therefore it is not surprising that noradrenergic and dopaminergic synaptic transmissions are affected adversely by in utero nicotinic exposure.Hypothesis: We hypothesize that fetal nicotine exposure delays the postnatal maturation of glutamatergic transmission onto dopamine neurons (DA) of the ventral tegmental area (VTA) in mice. These alterations may have an impact directly on proprieties of DA neurons and secondarily on target regions of dopaminergic system such as the prefrontal cortex (PFC), leading to neurobehavioral effects in the offspring. Aims: To test these hypotheses we propose the following specific aims:1.To determine the effects of nicotine fetal exposure on excitatory postsynaptic transmission onto DA neurons of the VTA during postnatal maturation, and the effects of nicotine on spine morphology. 2.To establish the developmental pattern of a4ß2 heteromeric channels and a7 homomeric channels in neurons of the VTA.3.To identify the nicotinic receptors, which drive the effects of nicotine in utero (distinguish between a4ß2 heteromeric channels and a7 homomeric channels).4.To elucidate the effects of prenatal nicotine exposure on DA neuron excitability and on the modulation of baseline neuronal communication within the cortico-limbic network.Research design: To achieve these aims we will expose pregnant mice to nicotine in utero and will use advance electrophysiological and pharmacological approach in acute slices of VTA and PFC of offspring in combination with in vivo electrophysiological recordings. We will also take advance of modern transfection technology and imaging of single neurons (2-photon line scanning microscopy, 2PLSM) in order to successfully address the questions raised here.Expected value: A successful completion of the present proposal may unravel cellular mechanisms underlying the pathological changes induced by nicotine in utero exposure.