- Email: [email protected]
Phasic dopamine neuron activity elicits unique mesofrontal plasticity in adolescence
Abstracts / Int. J. Devl Neuroscience 47 (2015) 1–131
cation and language disorders in socioenvironmentally vulnerable populations will be examined. http://dx.doi.org/10.1016/j.ijdevneu.2015.04.258 ISDN2014 0312 Phasic dopamine neuron activity elicits unique mesofrontal plasticity in adolescence Surjeet Mastwal 1 , Yizhou Ye 1 , Ming Ren 1 , Dennisse Jimenez 2 , Keri Martinowich 2,3 , Charles R. Gerfen 4 , Kuan Hong Wang 1,∗ 1
Unit on Neural Circuits and Adaptive Behaviors, Genes Cognition and Psychosis Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA 2 Lieber Institute for Brain Development, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA 3 Departments of Psychiatry & Behavioral Sciences and Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA 4 Laboratory of Systems Neuroscience, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA E-mail address: [email protected] (K.H. Wang). The mesofrontal dopaminergic circuit, which connects the midbrain motivation center to the cortical executive center, is engaged in the control of motivated behaviors. In addition, deficiencies in this circuit are associated with adolescent-onset psychiatric disorders in human. Developmental studies suggest that the mesofrontal circuit exhibits a protracted maturation through adolescence. However, whether the structure and function of this circuit are modifiable by activity in dopaminergic neurons during adolescence remains unknown. Here we show that phasic dopamine neuron activity, which is associated with motivated behaviors, elicits lasting structural and functional changes in the mesofrontal circuit during adolescence. Phasic optogenetic activation of dopamine neurons led to more boutons on their axons, potentiated mesofrontal circuit activities, and suppressed psychomotor responses, as revealed by in vivo two-photon imaging, electrophysiology, gene expression and behavioral analysis in adolescent mice. By contrast, in adulthood, the impacts of phasic activity on the mesofrontal circuit and psychomotor behavior were diminished. Our results demonstrate that phasic dopamine neuron activity elicits greater structural and functional changes of the mesofrontal circuit in adolescence than adulthood. The greater adolescent plasticity may facilitate activity-dependent strengthening of dopaminergic input and improvement in behavioral control. Our integrated optogenetic modulation and monitoring system may serve as a starting point for identifying molecular targets involved in activity-driven neurobiological changes during adolescence and for evaluating the potential impacts of therapeutic strategies on this circuit. http://dx.doi.org/10.1016/j.ijdevneu.2015.04.259
95
ISDN2014 0313 The development of functional connectivity in the neural network supporting waking J. Leung ∗ , S.H. Li, A. Lee, K.E. Godden, M. Pompeiano McGill University, Canada E-mail address: [email protected] (J. Leung). Adult wakefulness is sustained by the coordinated activity of interconnected neural circuitry collectively called the arousal system. One component of this system, the hypocretin/orexin (H/O) neurons of the hypothalamus, are key arousal promoters; they process information from both external and internal sources and consolidate arousal levels (Gao and Wang 2010) by directly activating Locus Coeruleus noradrenergic (LC-NA) neurons (as well as directly projecting to wide areas of the brain). Previous EEG and behavioral studies have suggested that embryos do not show waking (Mellor and Diesch 2007), but PET imaging has revealed the presence of different prenatal metabolic brain states correlated with arousal changes in chick embryos (Balaban et al., 2012). How the arousal system cell groups first become functionally connected during development and first become able to create different behavioral states is currently unknown. To better understand the development of functional connectivity between H/O and LC-NA neurons, we investigated spontaneous activity in H/O and LC-NA neurons in undisturbed chick embryos and neonatal (P1) awake chicks. Cell activity was evaluated using the expression of the immediate-early gene cFos. Relatively few H/O neurons were active on embryonic day (E) 12 (5–10%) compared with E16 (40%). The active population decreased significantly on E20 (10–30%) and in awake P1 animals showed levels similar to awake adult mammals (40%; Pompeiano et al., 2013). In contrast, activation of LC-NA neurons was very low prenatally (0% at E12, 5% at E16 and 15% at E20), also showing levels similar to awake adult mammals (40%) on P1. These different developmental activation signatures in H/O and LC-NA neurons suggest that these two systems are not functionally connected in undisturbed chick embryos until around hatching, in spite of the fact that H/O fibers and receptors are found in the LC at E12 (Cerazy et al., 2014). http://dx.doi.org/10.1016/j.ijdevneu.2015.04.260 ISDN2014 0314 Blast induces activation of brain stem/progenitor cells which generate cortical oligodendrocytes N. Nair 1,2,∗ , D. Freedman 1,2 , S. Narla 1,2 , S. Manohar 1 , M.K. Stachowiak 1,2 , R. Salvi 1 , E.K. Stachowiak 1,2 1
State University of New York at Buffalo, USA Western New York Stem Cells Culture and Analysis Center, Buffalo, NY 14214, USA 2
Sound blast induced brain injury is a major concern in military exposure to excessive noise. The effects of blast were examined by exposing adult mice 3 times to 190 decibels, with an interval of 3–4 min. The brain neural stem/progenitor cells were pre-labeled by injecting (i.p.) mice with BrdU prior to the blast. Mice were sacrificed and analyzed at 5 days (STB -short term blast) or 21 days (LTB-long term blast) after the blast. In the brain cortex (Cingulate Gyrus) of the STB mice we found a marked loss of myelinated fibers compared to sham control mice. In the LTB mice, brain images
cation and language disorders in socioenvironmentally vulnerable populations will be examined. http://dx.doi.org/10.1016/j.ijdevneu.2015.04.258 ISDN2014 0312 Phasic dopamine neuron activity elicits unique mesofrontal plasticity in adolescence Surjeet Mastwal 1 , Yizhou Ye 1 , Ming Ren 1 , Dennisse Jimenez 2 , Keri Martinowich 2,3 , Charles R. Gerfen 4 , Kuan Hong Wang 1,∗ 1
Unit on Neural Circuits and Adaptive Behaviors, Genes Cognition and Psychosis Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA 2 Lieber Institute for Brain Development, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA 3 Departments of Psychiatry & Behavioral Sciences and Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA 4 Laboratory of Systems Neuroscience, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA E-mail address: [email protected] (K.H. Wang). The mesofrontal dopaminergic circuit, which connects the midbrain motivation center to the cortical executive center, is engaged in the control of motivated behaviors. In addition, deficiencies in this circuit are associated with adolescent-onset psychiatric disorders in human. Developmental studies suggest that the mesofrontal circuit exhibits a protracted maturation through adolescence. However, whether the structure and function of this circuit are modifiable by activity in dopaminergic neurons during adolescence remains unknown. Here we show that phasic dopamine neuron activity, which is associated with motivated behaviors, elicits lasting structural and functional changes in the mesofrontal circuit during adolescence. Phasic optogenetic activation of dopamine neurons led to more boutons on their axons, potentiated mesofrontal circuit activities, and suppressed psychomotor responses, as revealed by in vivo two-photon imaging, electrophysiology, gene expression and behavioral analysis in adolescent mice. By contrast, in adulthood, the impacts of phasic activity on the mesofrontal circuit and psychomotor behavior were diminished. Our results demonstrate that phasic dopamine neuron activity elicits greater structural and functional changes of the mesofrontal circuit in adolescence than adulthood. The greater adolescent plasticity may facilitate activity-dependent strengthening of dopaminergic input and improvement in behavioral control. Our integrated optogenetic modulation and monitoring system may serve as a starting point for identifying molecular targets involved in activity-driven neurobiological changes during adolescence and for evaluating the potential impacts of therapeutic strategies on this circuit. http://dx.doi.org/10.1016/j.ijdevneu.2015.04.259
95
ISDN2014 0313 The development of functional connectivity in the neural network supporting waking J. Leung ∗ , S.H. Li, A. Lee, K.E. Godden, M. Pompeiano McGill University, Canada E-mail address: [email protected] (J. Leung). Adult wakefulness is sustained by the coordinated activity of interconnected neural circuitry collectively called the arousal system. One component of this system, the hypocretin/orexin (H/O) neurons of the hypothalamus, are key arousal promoters; they process information from both external and internal sources and consolidate arousal levels (Gao and Wang 2010) by directly activating Locus Coeruleus noradrenergic (LC-NA) neurons (as well as directly projecting to wide areas of the brain). Previous EEG and behavioral studies have suggested that embryos do not show waking (Mellor and Diesch 2007), but PET imaging has revealed the presence of different prenatal metabolic brain states correlated with arousal changes in chick embryos (Balaban et al., 2012). How the arousal system cell groups first become functionally connected during development and first become able to create different behavioral states is currently unknown. To better understand the development of functional connectivity between H/O and LC-NA neurons, we investigated spontaneous activity in H/O and LC-NA neurons in undisturbed chick embryos and neonatal (P1) awake chicks. Cell activity was evaluated using the expression of the immediate-early gene cFos. Relatively few H/O neurons were active on embryonic day (E) 12 (5–10%) compared with E16 (40%). The active population decreased significantly on E20 (10–30%) and in awake P1 animals showed levels similar to awake adult mammals (40%; Pompeiano et al., 2013). In contrast, activation of LC-NA neurons was very low prenatally (0% at E12, 5% at E16 and 15% at E20), also showing levels similar to awake adult mammals (40%) on P1. These different developmental activation signatures in H/O and LC-NA neurons suggest that these two systems are not functionally connected in undisturbed chick embryos until around hatching, in spite of the fact that H/O fibers and receptors are found in the LC at E12 (Cerazy et al., 2014). http://dx.doi.org/10.1016/j.ijdevneu.2015.04.260 ISDN2014 0314 Blast induces activation of brain stem/progenitor cells which generate cortical oligodendrocytes N. Nair 1,2,∗ , D. Freedman 1,2 , S. Narla 1,2 , S. Manohar 1 , M.K. Stachowiak 1,2 , R. Salvi 1 , E.K. Stachowiak 1,2 1
State University of New York at Buffalo, USA Western New York Stem Cells Culture and Analysis Center, Buffalo, NY 14214, USA 2
Sound blast induced brain injury is a major concern in military exposure to excessive noise. The effects of blast were examined by exposing adult mice 3 times to 190 decibels, with an interval of 3–4 min. The brain neural stem/progenitor cells were pre-labeled by injecting (i.p.) mice with BrdU prior to the blast. Mice were sacrificed and analyzed at 5 days (STB -short term blast) or 21 days (LTB-long term blast) after the blast. In the brain cortex (Cingulate Gyrus) of the STB mice we found a marked loss of myelinated fibers compared to sham control mice. In the LTB mice, brain images