Integrated Systems Approach
We create genetically modified laboratory animals that allow us to visualize and manipulate the different cells within the nervous system that express our genes of interest. A combination of genetic tailoring, viral neuronal tract-tracing and advanced microscopy is used to reveal the connectivity of neurons that express genes of interest. Optogenetics, chemogenetics, fMRI, and in vivo calcium imaging are used to determine how the activity of specific types of neurons is coupled to changes in physiology and behavior. Laboratory models of diseases (diet-induced obesity, social stressors) are implemented to understand the impact that stress has on gene expression, neuronal activity and connectivity. The information gleaned from our studies is used to identify novel therapeutic targets and interventions that can be validated against models of disease.
The Krause-de Kloet laboratory uses a variety of neuroanatomical techniques to reveal structural intricates that can be used to predict the function of specific connections within the nervous system.
Cre-LoxP genetic reporting:
Here, the Cre-LoxP system of genetic tailoring is used to direct the expression of tdTomato (red fluorescent protein) to all cells that express the gene encoding the angiotensin type 1a receptor.
Virally mediated gene transfer:
By administrating Cre-inducible viral constructs into the brain we reveal the connectivity and neurochemical phenotype of neurons in the prefrontal cortex that express oxytocin receptors
Coupling neuronal activity to physiology and behavior:
Optogenetics, chemogenetics, and in vivo calcium imaging are combined with behavioral paradigms and advanced physiological recordings to probe whether patterns of neuronal activity are linked to alterations to social behavior, feeding, endocrine release and indices of cardiometabolic function.