The dysfunction of multiple neurotransmitter systems is a striking pathophysiological feature of many mental disorders, schizophrenia in particular, but delineating the underlying mechanisms has been challenging. Here we show that manipulation of a single schizophrenia susceptibility gene, dysbindin, is capable of regulating both glutamatergic and dopaminergic functions through two independent mechanisms, consequently leading to two categories of clinically relevant behavioral phenotypes. Dysbindin has been reported to affect glutamatergic and dopaminergic functions as well as a range of clinically relevant behaviors in vertebrates and invertebrates but has been thought to have a mainly neuronal origin. We find that reduced expression of Drosophila dysbindin (Ddysb) in presynaptic neurons significantly suppresses glutamatergic synaptic transmission and that this glutamatergic defect is responsible for impaired memory. However, only the reduced expression of Ddysb in glial cells is the cause of hyperdopaminergic activities that lead to abnormal locomotion and altered mating orientation. This effect is attributable to the altered expression of a dopamine metabolic enzyme, Ebony, in glial cells. Thus, Ddysb regulates glutamatergic transmission through its neuronal function and regulates dopamine metabolism by regulating Ebony expression in glial cells.dystrobrevin binding protein 1 | glutamate | glia

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The learning curve in perceptual learning is typically sampled in blocks of trials, which could result in imprecise and possibly biased estimates, especially when learning is rapid. Recently, Zhao, Lesmes, and Lu (2017, 2019) developed a Bayesian adaptive quick Change Detection (qCD) method to accurately, precisely, and efficiently assess the time course of perceptual sensitivity change. In this study, we implemented and tested the qCD method in assessing the learning curve in a four-alternative forced-choice global motion direction identification task in both simulations and a psychophysical experiment. The stimulus intensity in each trial was determined by the qCD, staircase or random stimulus selection (RSS) methods. Simulations showed that the accuracy (bias) and precision (standard deviation or confidence bounds) of the estimated learning curves from the qCD were much better than those obtained by the staircase and RSS method; this is true for both trial-by-trial and post hoc segment-bysegment qCD analyses. In the psychophysical experiment, the average half widths of the 68.2% credible interval of the estimated thresholds from the trial-by-trial and post hoc segment-by-segment qCD analyses were both quite small. Additionally, the overall estimates from the qCD and staircase methods matched extremely well in this task where the behavioral rate of learning is relatively slow. Our results suggest that the qCD method can precisely and accurately assess the trialby-trial time course of perceptual learning.

Perceptual sensitivity is usually estimated over trials and time intervals, which results in imprecise and biased estimates when it changes rapidly over time. We develop a novel procedure, the quick Change-Detection (qCD) method, to accurately, precisely, and efficiently assess the time course of perceptual sensitivity change. Based on Bayesian adaptive testing, qCD selects the optimal stimulus, and updates, trial by trial, a joint probability distribution of the parameters that quantify perceptual sensitivity change over time. We demonstrate the utility of the method in measuring the time course of dark adaptation. Simulations showed that the accuracy and precision of the estimated dark adaptation curve after one qCD run (root mean squared error (RMSE): 0.002; the half width of the 68.2% credible interval (HWCI): 0.016; standard deviation (SD): 0.020; all in log10 units) was higher than those obtained by ten runs of the quick Forced-Choice (qFC) procedure (RMSE: 0.020; HWCI: 0.032; SD: 0.031) and ten runs of a weighted up-down staircase procedure (RMSE: 0.026; SD: 0.031). Further, the dark adaptation curve obtained from one qCD run in a psychophysics experiment was highly consistent with the average of four qFC runs (RMSE = 0.076 log10 units). Overall, the qCD may provide a procedure to characterize the time course of perceptual sensitivity change in both basic research and disease progression and treatment.