Hypofunction of cortico-basal ganglia circuits has been hypothesized to underlie some of the debilitating cognitive deficits and negative symptoms that are seen in schizophrenic patients. Antipsychotics are thought to mediate some of their therapeutic effects by normalizing this activity. However, the precise cell populations and the molecular changes involved in this response are still not fully understood. In Project 2 of this Conte center application, we hypothesize that cell-type specific changes in neurons projecting from the frontal cortex to the basal ganglia occur in response to typical and atypical antipsychotic drugs. To test this hypothesis, we will make use of a novel mRNA translational profiling approach.
In Aim 1 of this project, we will perform these studies on two distinct cortico-striatal cell populations we have targeted genetically.
In Aim 2, we will characterize two newly generated mouse lines that may give us translational profiling access to two additional cortico-striatal cell populations. Finally, in Aim 3, in collaboration with the other projects of this center, we will perform a functional analysis of molecules identified in our translational profiling studies of Aims 1 and 2.
to public health: Schizophrenia is a debilitating psychiatric disorder affecting - 1 % of the population. New therapeutic treatments for schizophrenia are needed. Project 2 will contribute to a more complete understanding of the cellular and molecular actions of antipsychotic drugs through biochemical studies of the actions of these drugs in specific populations of nerve cells.
|Milosevic, Ana; Liebmann, Thomas; Knudsen, Margarete et al. (2016) Cell- and region-specific expression of depression-related protein p11 (S100a10) in the brain. J Comp Neurol :|
|Xu, Jian; Kurup, Pradeep; Azkona, Garikoitz et al. (2016) Down-regulation of BDNF in cell and animal models increases striatal-enriched protein tyrosine phosphatase 61 (STEP61 ) levels. J Neurochem 136:285-94|
|Rapanelli, Maximiliano; Frick, Luciana R; Horn, Kyla D et al. (2016) The Histamine H3 Receptor Differentially Modulates Mitogen-activated Protein Kinase (MAPK) and Akt Signaling in Striatonigral and Striatopallidal Neurons. J Biol Chem 291:21042-21052|
|Uematsu, Ken; Heiman, Myriam; Zelenina, Marina et al. (2015) Protein kinase A directly phosphorylates metabotropic glutamate receptor 5 to modulate its function. J Neurochem 132:677-86|
|Wang, Hong; Warner-Schmidt, Jennifer; Varela, Santiago et al. (2015) Norbin ablation results in defective adult hippocampal neurogenesis and depressive-like behavior in mice. Proc Natl Acad Sci U S A 112:9745-50|
|Snyder, Gretchen L; Vanover, Kimberly E; Zhu, Hongwen et al. (2015) Functional profile of a novel modulator of serotonin, dopamine, and glutamate neurotransmission. Psychopharmacology (Berl) 232:605-21|
|Plattner, Florian; Hayashi, Kanehiro; HernÃ¡ndez, Adan et al. (2015) The role of ventral striatal cAMP signaling in stress-induced behaviors. Nat Neurosci 18:1094-100|
|Nakajima, Miho; GÃ¶rlich, Andreas; Heintz, Nathaniel (2014) Oxytocin modulates female sociosexual behavior through a specific class of prefrontal cortical interneurons. Cell 159:295-305|
|Dietz, David M; Kennedy, Pamela J; Sun, Haosheng et al. (2014) Ã½Ã½FosB induction in prefrontal cortex by antipsychotic drugs is associated with negative behavioral outcomes. Neuropsychopharmacology 39:538-44|
|Meyer, Douglas A; Torres-Altoro, Melissa I; Tan, Zhenjun et al. (2014) Ischemic stroke injury is mediated by aberrant Cdk5. J Neurosci 34:8259-67|
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