Disinhibition can account for the neural discoordination associated with impaired cognitive control

TitleDisinhibition can account for the neural discoordination associated with impaired cognitive control
Publication TypeConference Paper
Year of Publication2009
AuthorsFenton, A. A., Lee H., & Lytton WW.
Conference NameSociety for Neuroscience 2009 (SFN '09)
KeywordsSFN, Society for Neuroscience

There is now consensus that the core deficit in schizophrenia is an impairment in the cognitive control required to segregate relevant and irrelevant information. It has recently been found that markers of cortical inhibition are reduced in the post-mortem schizophrenic brain. Using combined physiological, behavioral and computational approaches, we present here a novel hypothesis that explains how impaired cognitive control could result from loss of inhibition. We, and others, have previously hypothesized that neural discoordination, a failure of action potential timing within neural ensembles, underlies the cognitive discoordination of schizophrenia through abnormal coactivity of cells representing irrelevant or unrelated information. In this prior work, we injected tetrodotoxin (TTX) into one dorsal hippocampus of the urethane-anaesthetized rat, and found firing alterations in the uninjected dorsal hippocampus. Specifically, pyramidal cell pairs became coactive if they had previously been unlikely to discharge together. This neural discoordination was associated with impaired cognitive control measured as an inability of awake rats with identical TTX treatment to segregate relevant and irrelevant spatial information in a two-frame spatial avoidance task. We have now found that the same TTX injection of one dorsal hippocampus silenced spiking in both the ipsilateral ventral and dorsal subdivisions, allowing us to determine what changes might occur in the contralateral (uninjected) ventral hippocampus due simply to absent activity without any local TTX effects. We found alterations similar to those observed in the contralateral dorsal hippocampus: 1. uncorrelated cell pairs became correlated. 2. no firing rate changes were observed. A neuronal network computer simulation confirmed that blockade of feed-forward inhibition via commissural excitation of inhibitory cells would produce selective coactivation of neuron pairs that were previously weakly coactive. These combined findings suggest that pathophysiological disinhibition could cause aberrant neural correlations that would underlie the core cognitive control deficits of schizophrenia.