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.
|Fox, Grace E; Li, Meng; Zhao, Fang et al. (2017) Distinct retrosplenial cortex cell populations and their spike dynamics during ketamine-induced unconscious state. PLoS One 12:e0187198|
|Li, Meng; Tsien, Joe Z (2017) Neural Code-Neural Self-information Theory on How Cell-Assembly Code Rises from Spike Time and Neuronal Variability. Front Cell Neurosci 11:236|
|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|
|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|
|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 Counting…. Front Genet 7:19|
|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|
|Tsien, Joe Z (2015) A Postulate on the Brain's Basic Wiring Logic. Trends Neurosci 38:669-671|
|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|
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