This year, new studies have revealed how early exon-dendritic interactions help to find synaptic partners in different categories. We took time to examine new data on identifying synaptogenic and antisynaptogenic factors that strengthen the connections, and how neuronal activity controls the expression of genes that shape and coordinate the formation and stability of neural circuits. In this examination we found that the synaptogenic and antisynaptogenic factors responsible for formation of synaptic networks control specificity and timing of synapse production, formation and maturation. Evidence is involving that neuronal activity promoted the development of neuronal circuits through activity-regulated genes, such as BDNF. For instance, the making of BDNF can be triggered through specific activity and this appears to promote development of cortical GABA synapses. All this information is useful in our studies and brings us to questions for the future. One challenge is to identify molecular mechanisms underlying the formation of synapses in specific brain regions, bring to light the distinct yet overlapping sets of genes that are regulated under different activity, and lastly, to unravel the spatial selectivity and temporal coordination of synapse development in neural circuits. In our investigations of the mechanisms by which experience-induced molecular changes impact on the subsequent cortical processing of sensory information. We continue to develop molecular genetics tools that would label behaviorally activated neurons in a spatially and temporally controlled manner, therefore facilitating optical tracking of activated neurons and their morphological changes. In addition, we are developing mouse genetics-based systems to optically activate or silence selected groups of neurons in order to probe their functional contributions to circuit outputs and adaptive behaviors. Our group continues to investigate the coupling mechanisms between sensory stimuli evoked neuronal activity and plasticity-related gene expression in cortical circuits, using calcium-sensitive fluorescent dyes and genetically encoded fluorescent reporters for the activity-regulated gene ARC. Particularly, we are examining whether the induction of activity-dependent gene expression is modified under the direct influence of specific neuromodulators that are associated with the motivational or emotional relevance of a given sensory experience. Finally, we are applying our opto-genetic systems to study cortical dysfunctions in the mouse models of schizophrenia as developed by the other research groups in the Genes, Cognition and Psychosis Program. In particular, by crossing transgenic mice carrying the risk alleles of candidate genes such as catechol-o-methyltransferase and potassium channel with our optical reporter and actuator lines, we can monitor the development of abnormal cortical circuits in real time, and investigate the interactions of genetic risk factors with environmental and social stressors.

Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2009
Total Cost
$1,023,668
Indirect Cost
Name
U.S. National Institute of Mental Health
Department
Type
DUNS #
City
State
Country
Zip Code
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Cao, Vania Yu; Ye, Yizhou; Mastwal, Surjeet et al. (2015) Motor Learning Consolidates Arc-Expressing Neuronal Ensembles in Secondary Motor Cortex. Neuron 86:1385-92
Mastwal, Surjeet; Ye, Yizhou; Ren, Ming et al. (2014) Phasic dopamine neuron activity elicits unique mesofrontal plasticity in adolescence. J Neurosci 34:9484-96

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