The cognitive problems of schizophrenia, which include difficulty planning and carrying out everyday tasks such as grocery shopping, are among the most disabling symptoms of the illness. They are also the ones that can have the biggest impact on a person’s quality of life. Researchers have found strong evidence that abnormalities in a particular type of cell – the parvalbumin or PV neuron – in the frontal cortex of the brain play a big role in these cognitive difficulties, but the exact ways in which this occurs have yet to be worked out. A trio of new studies used mouse models to take a closer look at how PV cell problems can cause cognitive symptoms.

One study, published March 2nd in the Proceedings of the National Academy of Sciences, reports the surprising finding that PV neurons in the basal forebrain, a brain area not yet implicated in schizophrenia, can control the rhythmic brain activity in frontal cortex that is crucial for normal cognitive function. Lead study authors Robert McCarley, M.D. (Foundation Scientific Council Member and former NARSAD Distinguished Investigator Grantee), and Ritchie Brown, Ph.D., from Boston’s Harvard Medical School, found that turning on these basal forebrain neurons in mice can enhance the this rhythmic brain activity, while silencing the PV cells can disturb the rhythms, similar to what is found in the brains of people with schizophrenia. The researchers hope their findings will encourage new research on basal forebrain PV neurons in schizophrenia. Additional NARSAD Grantees that participated in this study include 2012 NARSAD Young Investigator Grantee Jiwon Choi, Ph.D., and former NARSAD Young Investigator Grantees Lu Chen, Ph.D., and Karl Deisseroth, M.D., Ph.D. (Foundation Scientific Council Member).

In a second study, led by Vikaas Sohal, M.D., Ph.D., of the University of California, San Francisco, and published March 5th in Neuron, researchers disrupted PV neuron development in mice around adolescence. They found that this disruption led to the development of perturbed brain rhythms and cognitive problems in the mice around the same time, mirroring the usual timeline for the onset of schizophrenia symptoms.

In a third study, published online January 27th in Molecular Psychiatry, researchers led by Foundation Scientific Council Member and former NARSAD Grantee Karoly Mirnics, M.D., Ph.D., of Vanderbilt University in Nashville, report that mice with abnormal PV cells show cognitive difficulties that are reminiscent of those found in some people with schizophrenia. For example, the mice seem to have abnormally high levels of fear, which the researchers suggest could be similar to the paranoia sometimes seen in patients.

Learn more about this research at the Schizophrenia Research Forum.

Read the abstracts for each paper:

• March 2, 2015
• March 5, 2015
• January 27, 2015