Feb 17, 2012
Schizophrenia is a severe mental illness characterized by a constellation of symptoms. While a number of effective treatments for schizophrenia have been discovered, they only target the disease’s positive symptoms (e.g. hallucinations and delusions) and negative symptoms (e.g. flat affect). Even the newest commercially available antipsychotics are unable to treat the cognitive symptoms of the disease (e.g. impaired executive function, attention deficits, and working memory dysfunction).
Recent work has linked this pathology to deficits in inhibitory interneurons in the prefrontal cortex. These affected interneurons are important regulators of the timing and synchrony of neuronal firing. They have been implicated in the maintenance of gamma band oscillations, which are the synchronized firing of large neuronal networks at 30-80 Hz. Gamma band activity has been shown to be an important aspect of the maintenance of attention and working memory. Notably, schizophrenics exhibit abnormalities in their gamma oscillations when given tests of their working memory.
Recent evidence has suggested that the primary deficit in these interneurons may involve hypofunctional glutamic acid decarboxylase (GAD). GAD is the enzyme responsible for synthesizing GABA in neurons. For my project, I will be infusing L-allyl glycine (LAG), a GAD inhibitor, into the medial prefrontal cortex of rats. I will then assess the rats’ attentional capabilities using the 5-choice serial reaction time task (5CSRTT). I hypothesize that LAG administration will lead to performance deficits in the 5CSRTT.