Thursday, October 12th - 4:00pm to 5:00pm

MIT Colloquium on the Brain and Cognition

Dysfunction of GABAergic interneurons and neuropsychiatric illnesses

Kazutoshi Nakazawa
Singleton Auditorium 46-3002
Public welcome

Santiago Ramon y Cajal called cortical interneurons 'mysterious butterflies of the soul’.  In recent years, this prescient metaphor has been amply borne out by experiments suggesting that such basic mental functions as memory, cognition, attention, and perception depend on cortical interneurons maintaining the proper excitatory-inhibitory (E/I) balance. However, E/I balance takes place in many mental disorders such as schizophrenia, major depressive disorder, autism, and intellectual disabilities.  Therefore, there may be more specific alterations in the development and function of types of interneuron that are implicated in the development of mental illnesses. We have explored the functional outcomes of cortical interneurons’ dysfunction by genetically ablating some synaptic protein in a cell-type specific manner. The first example is modeling schizophrenia-like phenotype in mice, in which we deleted glutamatergic NMDA receptor subunitGrin1 in some of cortical and hippocampal interneurons of mainly parvalbumin-containing during early postnatal development. Consistent with an NMDA receptor hypofunction theory for schizophrenia, the mutant mice recapitulated some schizophrenia-like phenotypes, including striatal hyper-dopamine/prefrontal hypo-dopamine release, impaired auditory-steady-state responses (ASSRs), and high vulnerability to oxidative stress. The second example that I would like to briefly mention is an effort-based behavioral deficit in mice where cortical GABA level is reduced by genetic deletion of GABA synthesizing enzyme GAD67 in the cortex, including mPFC, and hippocampus. This negative symptom-like phenotype appears to be associated with an effort-triggered dopamine release deficit in the anterior cingulate cortex (ACC) of the mutant mice.  Overall, our research suggests critical importance of elucidating disease-specific aspects of cortical GABAergic dysfunction.   Such investigation will pave the way for better understanding of neural basis of mental function and the causes of neuropsychiatric illnesses.  

Yingxi Lin
Speaker Bio: 

Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, Alabama, USA.