RESUMO
Understanding the neural mechanisms of working memory has been a long-standing Neuroscience goal. Bump attractor models have been used to simulate persistent activity generated in the prefrontal cortex during working memory tasks and to study the relationship between activity and behavior. How realistic the assumptions of these models are has been a matter of debate. Here, we relied on an alternative strategy to gain insights into the computational principles behind the generation of persistent activity and on whether current models capture some universal computational principles. We trained Recurrent Neural Networks (RNNs) to perform spatial working memory tasks and examined what aspects of RNN activity accounted for working memory performance. Furthermore, we compared activity in fully trained networks and immature networks, achieving only imperfect performance. We thus examined the relationship between the trial-to-trial variability of responses simulated by the network and different aspects of unit activity as a way of identifying the critical parameters of memory maintenance. Properties that spontaneously emerged in the artificial network strongly resembled persistent activity of prefrontal neurons. Most importantly, these included drift of network activity during the course of a trial that was causal to the behavior of the network. As a consequence, delay period firing rate and behavior were positively correlated, in strong analogy to experimental results from the prefrontal cortex. These findings reveal that delay period activity is computationally efficient in maintaining working memory, as evidenced by unbiased optimization of parameters in artificial neural networks, oblivious to the properties of prefrontal neurons.
RESUMO
CD306, also known as soluble leukocyte-associated immunoglobulin-like receptor-2 (LAIR-2), is a member of an immunoglobulin superfamily with the shared characteristic of an immunoglobulin-like C2-type domain. CD306 is speculated to be secretory and has 84% similarity with the extracellular domain of CD305, which binds to the same ligands as CD306. However, data on its distribution are absent due to the lack of an efficient method to detect it. In this study, we successfully cloned the cDNA of CD306 from the peripheral blood mononuclear cells (PBMCs) of patients with hemorrhagic fever with renal syndrome. The fusion proteins were expressed and purified, and three strains of monoclonal antibodies (mAbs) against CD306 were prepared and characterized. The sandwich ELISA for detecting CD306 was established and optimized with sensitivity up to 15 pg/ml, and the assay showed high specificity for the detection of CD306. With this method, a right skewed frequency distribution of CD306 in the sera of healthy subjects was determined. The concentrations of CD306 in sera and urine were detected in patients with different diseases. Aberrantly high levels of CD306 were found in the sera of pregnant women and patients with inflammation and rheumatic heart disease and in the urine of pregnant women. Meanwhile, there was a positive correlation between CD306 and soluble CD305 expression and secretion levels in sera and urine samples from patients, and both proteins inhibited CD305-mediated immunosuppressive functions. Our results demonstrate that CD306 represents a potentially useful predictor for disease diagnosis and that the method developed has potential for clinical application.
