Impaired motor skill and habit-learning deficits have often been observed in Parkinson's disease patients well before the onset of clinically identifiable movement disorders, indicating that dopamine plays an important role in procedural habit learning. However, activities of midbrain dopaminergic (DA) neurons are regulated by cortical and subcortical signals among which glutamatergic afferents provide excitatory inputs. In this application, we set out to genetically examine the role of the NMDA receptor in the dopamine neural circuitry, namely, the ventral tegmental area and substantia nigra pars compacta as well as in the striatum in habit learning. We will generate a series of region-specific and inducible NMDA receptor knockout mouse lines to define the temporal stages during which habit is formed and stored. We will further combine conditional knockout mice with optogentic and neural ensemble recording techniques to systematically investigate the roles of the DA neuron NMDA receptor in neural dynamical patterns associated with habit learning. We believe that this integrated approach may provide us not only with important insight into the molecular and temporal mechanisms of habit learning, but also with potential novel therapeutic strategies for preventing and treating Parkinson's disease.
Decoding the upstream pathways regulating dopamine is crucial for understanding habit learning. This application will apply a set of molecular genetics and neural ensemble recording techniques to investigate the NMDA receptor-mediated molecular and temporal mechanisms of habit formation in the dopaminergic neural circuitry in the brain.
|Xie, Kun; Fox, Grace E; Liu, Jun et al. (2016) 512-Channel and 13-Region Simultaneous Recordings Coupled with Optogenetic Manipulation in Freely Behaving Mice. Front Syst Neurosci 10:48|
|Xie, Kun; Fox, Grace E; Liu, Jun et al. (2016) Brain Computation Is Organized via Power-of-Two-Based Permutation Logic. Front Syst Neurosci 10:95|
|Tsien, Joe Z (2016) Cre-Lox Neurogenetics: 20 Years of Versatile Applications in Brain Research and Countingâ€¦. Front Genet 7:19|
|Li, Meng; Liu, Jun; Tsien, Joe Z (2016) Theory of Connectivity: Nature and Nurture of Cell Assemblies and Cognitive Computation. Front Neural Circuits 10:34|
|Lee, Jason C; Wang, Lei Philip; Tsien, Joe Z (2016) Dopamine Rebound-Excitation Theory: Putting Brakes on PTSD. Front Psychiatry 7:163|
|Tsien, Joe Z (2015) Principles of Intelligence: On Evolutionary Logic of the Brain. Front Syst Neurosci 9:186|
|Li, Meng; Zhao, Fang; Lee, Jason et al. (2015) Computational Classification Approach to Profile Neuron Subtypes from Brain Activity Mapping Data. Sci Rep 5:12474|
|Tsien, Joe Z (2015) A Postulate on the Brain's Basic Wiring Logic. Trends Neurosci 38:669-71|
|Tsien, Joe Z; Li, Meng; Osan, Remus et al. (2013) On initial Brain Activity Mapping of episodic and semantic memory code in the hippocampus. Neurobiol Learn Mem 105:200-10|
|Liu, Jun; Wei, Wei; Kuang, Hui et al. (2013) Changes in heart rate variability are associated with expression of short-term and long-term contextual and cued fear memories. PLoS One 8:e63590|
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