A main objective of the Animal Models Core is to provide a broad range of behavioral models of stimulant and opiate addiction in mice and rats to support the PPG's overall goal to establish molecular, cellular, and circuit mechanisms of addiction. Such models include several routine behavioral assays as well as more sophisticated self-administration, self-stimulation, and cognition paradigms. The imperative to employ this broad behavioral battery is that it is difficult to infer something about such a complex behavioral syndrome as addiction from a single model or even a limited number of models. The Core then utilizes these behavioral resources in two main ways. First, the Core provides microdissections of brain reward regions from carefully defined mouse models for molecular characterization in each Project and in the Chromatin and Gene Analysis Core. Second, the Core works with each of the four Projects to generate causal evidence that directly links specific molecular, cellular, and circuit-level adaptations to particular behavioral abnormalities that define a state of addiction. The Core accomplishes this goal by providing a range of genetic mutant mice as well as a large number of vectors for viral-mediated gene transfer, all of which are extensively validated by the Core. The mice and vectors are often generated initially to meet the specific needs of an individual Project, but then are provided to other Projects to broaden their application and thereby promote PPG integration. This Core has led the field in generating mutant mice and viral vectors, which make it possible to selectively manipulate a given gene of interest within a particular neuronal cell type or brain region of adult animals, thus avoiding confounds with more traditional approaches. Finally, the Core provides advanced optogenetic tools to Project investigators to directly implicate altered neuronal and circuit function to addiction-related behavioral abnormalities. By consolidating this behavioral, mouse mutagenesis, viral vector, and optogenetic work within a centralized Core, we ensure rigorous control over the data and facilitate comparisons and contrasts of experimental results across the individual Projects. This consolidation also makes financial sense, since we concentrate and maximize efficient use of the required expertise.
Addiction remains one of the world's greatest public health problems, yet its pathophysiology remains incompletely understood and available treatments for addictions to various drugs of abuse are inadequately effective for most people. We believe that the most effective way of eventually developing definitive treatments and cures for addiction rests in part in a better understanding of its underlying neurobiology.
|Gokce, Ozgun; Stanley, Geoffrey M; Treutlein, Barbara et al. (2016) Cellular Taxonomy of the Mouse Striatum as Revealed by Single-Cell RNA-Seq. Cell Rep 16:1126-37|
|Fuccillo, Marc V; Rothwell, Patrick E; Malenka, Robert C (2016) From Synapses to Behavior: What Rodent Models Can Tell Us About Neuropsychiatric Disease. Biol Psychiatry 79:4-6|
|Kozlenkov, Alexey; Wang, Minghui; Roussos, Panos et al. (2016) Substantial DNA methylation differences between two major neuronal subtypes in human brain. Nucleic Acids Res 44:2593-612|
|Cahill, Michael E; Bagot, Rosemary C; Gancarz, Amy M et al. (2016) Bidirectional Synaptic Structural Plasticity after Chronic Cocaine Administration Occurs through Rap1 Small GTPase Signaling. Neuron 89:566-82|
|Calipari, Erin S; Bagot, Rosemary C; Purushothaman, Immanuel et al. (2016) In vivo imaging identifies temporal signature of D1 and D2 medium spiny neurons in cocaine reward. Proc Natl Acad Sci U S A 113:2726-31|
|Wang, Tianyuan; Santos, Janine H; Feng, Jian et al. (2016) A Novel Analytical Strategy to Identify Fusion Transcripts between Repetitive Elements and Protein Coding-Exons Using RNA-Seq. PLoS One 11:e0159028|
|Graziane, Nicholas M; Sun, Shichao; Wright, William J et al. (2016) Opposing mechanisms mediate morphine- and cocaine-induced generation of silent synapses. Nat Neurosci 19:915-25|
|Khibnik, Lena A; Beaumont, Michael; Doyle, Marie et al. (2016) Stress and Cocaine Trigger Divergent and Cell Type-Specific Regulation of Synaptic Transmission at Single Spines in Nucleus Accumbens. Biol Psychiatry 79:898-905|
|Kiraly, Drew D; Walker, Deena M; Calipari, Erin S et al. (2016) Alterations of the Host Microbiome Affect Behavioral Responses to Cocaine. Sci Rep 6:35455|
|Egervari, Gabor; Landry, Joseph; Callens, James et al. (2016) Striatal H3K27 Acetylation Linked to Glutamatergic Gene Dysregulation in Human Heroin Abusers Holds Promise as Therapeutic Target. Biol Psychiatry :|
Showing the most recent 10 out of 267 publications