The therapeutic potential of the cerebellum in schizophrenia



 DESCRIPTION (provided by applicant): Candidate: Dr. Krystal Parker is a postdoctoral research scholar in the Department of Neurology at the University of Iowa. She has an outstanding systems neuroscience background with a PhD in cerebellar circuitry and clinical training in cerebellar involvement in neuropsychiatric illness. Her primary research interests involve investigating mechanisms to harness the cerebellum to treat cognitive dysfunction in neuropsychiatric illness. Career Development: This award will 1) ensure Dr. Parker finalizes training in advanced systems neuroscience techniques such as multisite neuronal recordings paired with optogenetics and 2) is poised to make a smooth transition to an independent scientist focused on developing new treatments for patients suffering cognitive abnormalities stemming from neurological and psychiatric disease. This proposal will optimally position Dr. Parker for an independent career translating insights on the functional role of basic cerebellar circuitry into therapies that could help patients with cognitive dysfunction. Research Strategy: There are currently no effective treatments for cognitive dysfunction in neuropsychiatric illness as the underlying mechanisms are unknown. Dr. Parker and the Narayanan laboratory study cognitive deficits using an interval timing task. This task is ideally suited to study the basic circuitry of cognition in schizophrenia as patients have reliable deficits, task performance depends on known prefrontal circuitry, and it can be investigated in animals displaying schizophrenia-like phenotypes. The cerebellum is essential for cognition and Dr. Parker's preliminary data show that it is also required for interval timing. In addition, the cerebellum and prefrontal cortex are both consistently dysfunctional in schizophrenia patients suffering from cognitive dysfunction. Dr. Parker's preliminary data recapitulates timing deficits with disruption f both brain areas in animal models. Her overall goal is to develop an independent laboratory that focuses on leveraging the cerebellar connections to the frontal cortex to develop novel therapies in schizophrenia. The proposed experiments combine cutting-edge techniques to test the hypothesis that the cerebellum modulates dysfunctional prefrontal circuits impaired in schizophrenia. We expect that insights from this research will guide future therapies for patients suffering from impaired cognition. Mentors and Consultants: For this proposal, Dr. Parker has identified a strong mentoring team. Her primary mentors will be Dr. Narayanan, an innovative systems neuroscientist and neurologist who will teach her techniques for optogenetics, neuronal ensemble recordings, and data analysis. In parallel, she will work with senior established mentor, Dr. William Talman, who will intensively mentor her in many of the career development aspects during her postdoctoral fellowship period but also in immunohistochemistry using confocal microscopy. Dr. John Freeman will informally consult with Dr. Parker in aspects of cerebellar dependent behavior, cerebellar neuronal recordings, and cerebellar histology. Dr. Parker recognizes her need for mentors in schizophrenia and has joined forces with Drs. Bita Moghaddam and Mikhail Pletnikov, experts in experimental protocols in animals that are potentially relevant to schizophrenia. She will visit their laboratories to learn their methods, be immersed in their research programs, and discuss her results and experimental designs with them and their lab members. Environment: The University of Iowa boasts an exceptional research environment with leaders in neuropsychiatric research. In addition, the Department of Neurology strongly supports the candidate and will provide all the resources necessary for Dr. Parker to complete her proposed experiments and facilitate her transition to independence.