Encoding and retrieval of artificial visuoauditory memory traces in the auditory cortex requires the entorhinal cortex.

Damage to the medial temporal lobe impairs the encoding of new memories and the retrieval of memories acquired immediately before the damage in human. In this study, we demonstrated that artificial visuoauditory memory traces can be established in the rat auditory cortex and that their encoding and retrieval depend on the entorhinal cortex of the medial temporal lobe in the rat. We trained rats to associate a visual stimulus with electrical stimulation of the auditory cortex using a classical conditioning protocol. After conditioning, we examined the associative memory traces electrophysiologically (i.e., visual stimulus-evoked responses of auditory cortical neurons) and behaviorally (i.e., visual stimulus-induced freezing and visual stimulus-guided reward retrieval). The establishment of a visuoauditory memory trace in the auditory cortex, which was detectable by electrophysiological recordings, was achieved over 20-30 conditioning trials and was blocked by unilateral, temporary inactivation of the entorhinal cortex. Retrieval of a previously established visuoauditory memory was also affected by unilateral entorhinal cortex inactivation. These findings suggest that the entorhinal cortex is necessary for the encoding and involved in the retrieval of artificial visuoauditory memory in the auditory cortex, at least during the early stages of memory consolidation.

Time course of the dependence of associative memory retrieval on the entorhinal cortex.

As the gateway between the hippocampal system and the neocortex, the entorhinal cortex (EC) is hypothesized to be the hub in which the transformation of recent memory to remote memory is processed. We explored the role of the EC on the retrieval of recent and remote associative fear memory. A within-subject approach was adopted to compare the freezing rates of rats in EC intact and EC inactivated conditions following trace fear conditioning. The EC was inactivated by infusing an AMPA antagonist. The fear conditioning used a combined visual and auditory conditioned stimulus with a foot shock. On week 1 following the conditioning, the rats in the EC intact condition exhibited a freezing rate of 92.4±9.5% in response to the light stimulus compared with a 6.3±7.9% freezing rate in the EC inactivated condition. The freezing rates were 87.0±17.8% and 4.7±6.5% on week 2 in the EC intact and inactivated conditions, respectively. These results indicate that the EC participates in the retrieval of associative memory. Extinction of the fear memory was observed in the EC intact condition, as the mean freezing rate decreased to 62.7±23.0% on week 4 and 41.2±26.4% on week 5. However, the freezing rate increased to 26.8±14.2% on week 4 and 22.3±14.4% on week 5 in the EC inactivated condition. The normalized dependence of fear memory retrieval on the EC was 93.2±8.3% on week 1, and significantly decreased on weeks 4 and 5. In summary, the retrieval of associative memory depends on the EC, but this dependence decreases over time.

A Novel Graphic-Aided Algorithm (gNIPT) Improves the Accuracy of Noninvasive Prenatal Testing.

Noninvasive Prenatal Testing (NIPT) has advanced the detection of fetal chromosomal aneuploidy by analyzing cell-free DNA in peripheral maternal blood. The statistic Z-test that it utilizes, which measures the deviation of each chromosome dosage from its negative control, is now widely accepted in clinical practice. However, when a chromosome has loss and gain regions which offset each other in the z-score calculation, merely using the Z-test for the result tends to be erroneous. To improve the performance of NIPT in this aspect, a novel graphic-aided algorithm (gNIPT) that requires no extra experiment procedures is reported in this study. In addition to the Z-test, this method provides a detailed analysis of each chromosome by dividing each chromosome into multiple 2 Mb size windows, calculating the z-score and copy number variation of each window, and visualizing the z-scores for each chromosome in a line chart. Data from 13537 singleton pregnancy women were analyzed and compared using both the normal NIPT (nNIPT) analysis and the gNIPT method. The gNIPT method had significantly improved the overall positive predictive value (PPV) of nNIPT (88.14% vs. 68.00%, p = 0.0041) and the PPV for trisomy 21 (T21) detection (93.02% vs. 71.43%, p = 0.0037). There were no significant differences between gNIPT and nNIPT in PPV for trisomy 18 (T18) detection (88.89% vs. 63.64%, p = 0.1974) and in PPV for trisomy 13 (T13) detection (57.14% vs. 50.00%, p = 0.8004). One false-negative T18 case in nNIPT was detected by gNIPT, which demonstrates the potency of gNIPT in discerning chromosomes that have variation in multiple regions with an offsetting effect in z-score calculation. The gNIPT was also able to detect copy number variation (CNV) in chromosomes, and one case with pathogenic CNV was detected during the study. With no additional test requirement, gNIPT presents a reasonable solution in improving the accuracy of normal NIPT.