The Cre/lox system is widely used in mice to achieve cell-type-specific gene expression. However, a strong and universally responding system to express genes under Cre control is still lacking. We have generated a set of Cre reporter mice with strong, ubiquitous expression of fluorescent proteins of different spectra. The robust native fluorescence of these reporters enables direct visualization of fine dendritic structures and axonal projections of the labeled neurons, which is useful in mapping neuronal circuitry, imaging and tracking specific cell populations in vivo. Using these reporters and a high-throughput in situ hybridization platform, we are systematically profiling Cre-directed gene expression throughout the mouse brain in several Cre-driver lines, including new Cre lines targeting different cell types in the cortex. Our expression data are displayed in a public online database to help researchers assess the utility of various Cre-driver lines for cell-type-specific genetic manipulation.

/pdf/a-robust-and-high-throughput-cre-reporting-and-4ytqviywww.pdf

A robust and high-throughput Cre reporting and characterization system for the whole mouse brain

The dopamine hypothesis of schizophrenia has been one of the most enduring ideas in psychiatry. Initially, the emphasis was on a role of hyperdopaminergia in the etiology of schizophrenia (version I), but it was subsequently reconceptualized to specify subcortical hyperdopaminergia with prefrontal hypodopaminergia (version II). However, these hypotheses focused too narrowly on dopamine itself, conflated psychosis and schizophrenia, and predated advances in the genetics, molecular biology, and imaging research in schizophrenia. Since version II, there have been over 6700 articles about dopamine and schizophrenia. We selectively review these data to provide an overview of the 5 critical streams of new evidence: neurochemical imaging studies, genetic evidence, findings on environmental risk factors, research into the extended phenotype, and animal studies. We synthesize this evidence into a new dopamine hypothesis of schizophrenia-version III: the final common pathway. This hypothesis seeks to be comprehensive in providing a framework that links risk factors, including pregnancy and obstetric complications, stress and trauma, drug use, and genes, to increased presynaptic striatal dopaminergic function. It explains how a complex array of pathological, positron emission tomography, magnetic resonance imaging, and other findings, such as frontotemporal structural and functional abnormalities and cognitive impairments, may converge neurochemically to cause psychosis through aberrant salience and lead to a diagnosis of schizophrenia. The hypothesis has one major implication for treatment approaches. Current treatments are acting downstream of the critical neurotransmitter abnormality. Future drug development and research into etiopathogenesis should focus on identifying and manipulating the upstream factors that converge on the dopaminergic funnel point.

/pdf/the-dopamine-hypothesis-of-schizophrenia-version-iii-the-3pqlczm8om.pdf

The Dopamine Hypothesis of Schizophrenia: Version III—The Final Common Pathway

Modeling of human neuropsychiatric disorders in animals is extremely challenging given the subjective nature of many symptoms, the lack of biomarkers and objective diagnostic tests, and the early state of the relevant neurobiology and genetics. Nonetheless, progress in understanding pathophysiology and in treatment development would benefit greatly from improved animal models. Here we review the current state of animal models of mental illness, with a focus on schizophrenia, depression and bipolar disorder. We argue for areas of focus that might increase the likelihood of creating more useful models, at least for some disorders, and for explicit guidelines when animal models are reported.

/pdf/animal-models-of-neuropsychiatric-disorders-1w7jb15e05.pdf

Animal models of neuropsychiatric disorders

Inverted-U-shaped dopamine actions on human working memory and cognitive control.

Resolving Emotional Conflict: A Role for the Rostral Anterior Cingulate Cortex in Modulating Activity in the Amygdala

Transient and selective overexpression of dopamine D2 receptors in the striatum causes persistent abnormalities in prefrontal cortex functioning.

Psychotherapy is used commonly to treat a variety of mental illnesses, yet surprisingly little is known about its biological mechanisms especially in comparison with pharmacotherapy. In this review we survey the current knowledge about changes in brain function following psychotherapeutic intervention that are detectable with current neuroimaging techniques. We also consider the possible role for neuroimaging in refining clinical diagnoses and predicting treatment outcome, which would benefit both clinical decision-making and the cognitive neuroscience of psychotherapy.

Toward a neurobiology of psychotherapy: basic science and clinical applications.

Psychobiological origins of infant attachment and separation responses.

https://psychophysiology.cpmc.columbia.edu/pdf/xu2007a.pdf

DRD2 C957T polymorphism interacts with the COMT Val158Met polymorphism in human working memory ability.

The Structured Clinical Interview for DSM-III-R (SCID-I) and the Adult Attachment Interview (AAI) were administered to 60 women participating in a study (n = 226) of mother – child interaction. These women were not referred to the study for psychiatric care. The 60 women interviewed with the AAI were selected from the first 190 women who completed the SCID-I, so that 30 received a diagnosis and 30 did not. Analyses indicated that psychopathology diagnoses were associated significantly with mental representations of attachment classified in the AAI. The non-autonomous groups had increased likelihood of SCID diagnosis, compared to the autonomous group. While 32% of women with autonomous AAI transcripts received SCID diagnoses, 63% of women with Dismissing, 100% of woman with Preoccupied, and 65% of women with Unresolved transcripts received diagnoses. Secondary analyses indicated that Dismissing classifications were associated with Axis I diagnoses and Preoccupied classifications with affective dis...

H. Jonathan Polan

Papers

Transient and selective overexpression of dopamine D2 receptors in the striatum causes persistent abnormalities in prefrontal cortex functioning.

Toward a neurobiology of psychotherapy: basic science and clinical applications.

Psychobiological origins of infant attachment and separation responses.

DRD2 C957T polymorphism interacts with the COMT Val158Met polymorphism in human working memory ability.

Attachment and psychopathology in a community sample.