SUMMARY Subtypes of GABAergic interneurons (INs) are crucial for cortical function, yet their specific roles are largely unknown. In contrast to supra- and infra-granular layers, where most somatostatin-expressing (SOM) INs are layer 1-targeting Martinotti cells, the axons of SOM INs in layer 4 somatosensory cortex largely remain within layer 4. Moreover, we found that whereas layers 2/3 SOM INs target mainly pyramidal cells (PCs), layer 4 SOM INs target mainly fast-spiking (FS) INs. Accordingly, optogenetic inhibition of SOM INs in an active cortical network increases the firing of layers 2/3 PCs whereas decreases the firing of layer 4 principal neurons (PNs). This unexpected effect of SOM INs on layer 4 PNs occurs via their inhibition of local FS INs. These results reveal a novel disinhibitory microcircuit in the thalamorecipient layer through interactions among subtypes of GABAergic INs, and suggest that SOM IN-mediated disinhibition represents an important circuit mechanism for cortical processing.

The accuracy of NIPT for ChrX and ChrY can be improved substantially by integrating the results of maternal-plasma sequencing with those for maternal-WBC sequencing. The relatively high frequency of maternal mosaicism warrants mandatory WBC testing in both shotgun sequencing- and single-nucleotide polymorphism-based clinical NIPT after the finding of a potential fetal SCA.

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Although previous work identified transcription factors crucial for the specification and migration of parvalbumin (PV) and somatostatin (SST)-expressing interneurons, the intrinsic factors required for the terminal differentiation, connectivity and survival of these cell types remain uncharacterized. Here we demonstrate that, within subpopulations of cortical interneurons, the special AT-rich binding protein (Satb1) functions in this capacity. We find that conditional removal of Satb1 in mouse interneurons results in the loss of a majority of SST-expressing cells across all cortical layers, as well as some PV-expressing cells in layers IV and VI, by postnatal day 21. SST-expressing cells initially migrate to the cortex in Satb1 mutant mice, but receive reduced levels of afferent input and begin to die during the first postnatal week. Electrophysiological characterization indicates that loss of Satb1 function in interneurons results in a loss of functional inhibition of excitatory principal cells. These data suggest that Satb1 is required for MGE-derived interneuron differentiation, connectivity and survival.

Although sensorineural hearing loss (SNHL) is known to compromise central auditory structure and function, the impact of milder forms of hearing loss on cellular neurophysiology remains mostly undefined. We induced conductive hearing loss (CHL) in developing gerbils, reared the animals for 8 -13 d, and subsequently assessed the temporal features of auditory cortex layer 2/3 pyramidal neurons in a thalamocortical brain slice preparation with whole-cell recordings. Repetitive stimulation of the ventral medial geniculate nucleus (MGv) evoked robust short-term depression of the postsynaptic potentials in control neurons, and this depression increased monotonically at higher stimulation frequencies. In contrast, CHL neurons displayed a faster rate of synaptic depression and a smaller asymptotic amplitude. Moreover, the latency of MGv evoked potentials was consistently longer in CHL neurons for all stimulus rates. A separate assessment of spike frequency adaptation in response to trains of injected current pulses revealed that CHL neurons displayed less adaptation compared with controls, although there was an increase in temporal jitter. For each of these properties, nearly identical findings were observed for SNHL neurons. Together, these data show that CHL significantly alters the temporal properties of auditory cortex synapses and spikes, and this may contribute to processing deficits that attend mild to moderate hearing loss.

Cognitive behavior therapy (CBT) is effective for the treatment of Internet gaming disorder (IGD). However, the mechanisms by which CBT improves IGD-related clinical symptoms remain unknown. This study aimed to discover the therapeutic mechanism of CBT in IGD subjects using resting-state functional magnetic resonance imaging (rsfMRI). Twenty-six IGD subjects and 30 matched healthy controls (HCs) received rsfMRI scan and clinical assessments; 20 IGD subjects completed CBT and then were scanned again. The amplitude of low-frequency (ALFF) values and the functional connectivity (FC) between the IGD group and the HC group were compared at baseline, as well as the ALFF values and FC before and after the CBT in the IGD group. Prior to treatment, the IGD group exhibited significantly increased ALFF values in the bilateral putamen, the right medial orbitofrontal cortex (OFC), the bilateral supplementary motor area (SMA), the left postcentral gyrus, and the left anterior cingulate (ACC) compared with the HC group. The HC group showed significantly increased FC values between the left medial OFC and the putamen compared with the IGD group, the FC values of IGD group were negatively associated with the BIS-11 scores before treatment. After the CBT, the weekly gaming time was significantly shorter, and the CIAS and BIS-II scores were significantly lower. The ALFF values in the IGD subjects significantly decreased in the left superior OFC and the left putamen, and the FC between them significantly increased after the CBT. The degree of the FC changes (ΔFC/Pre−FC) was positively correlated with the scale of the CIAS scores changes (ΔCIAS/Pre−CIAS) in the IGD subjects. CBT could regulate the abnormal low-frequency fluctuations in prefrontal-striatal regions in IGD subjects and could improve IGD-related symptoms. Resting-state alternations in prefrontal-striatal regions may reveal the therapeutic mechanism of CBT in IGD subjects.

What's already known about this topic? Confined placental mosaicism (CPM) is a known biological phenomenon that can lead to false positive non-invasive prenatal test results. The small number of false negative non‐invasive prenatal test results reported to date are believed to be because of a low fetal DNA fraction in maternal plasma and/or placental mosaicism What does this study add? The degree and compartmentalization of placental mosaicism can potentially reduce the effective output of fetal DNA into the maternal circulation to steady state levels below the detection limit of non‐invasive prenatal testing, leading to a false negative result

Long-term synaptic plasticity is a putative mechanism for learning in adults. However, there is little understanding of how synaptic plasticity mechanisms develop or whether their maturation depends on experience. Since inhibitory synapses are particularly malleable to sensory stimulation, long-lasting potentiation of inhibitory synapses was characterized in auditory thalamocortical slices. Intracortical high-frequency electrical stimulation led to a 67% increase in inhibitory synaptic currents. In the absence of stimulation, inhibitory potentiation was induced by a brief exposure to exogenous brain-derived neurotrophic factor (BDNF). BDNF exposure occluded any additional potentiation by high-frequency afferent stimulation, suggesting that BDNF signaling is sufficient to account for inhibitory potentiation. Moreover, inhibitory potentiation was reduced significantly by extracellular application of a BDNF scavenger or by intracellular blockade of BDNF receptor [tropomyosin-related kinase B (TrkB)] signaling. In contrast, glutamatergic or GABAergic antagonists did not prevent the induction of inhibitory potentiation. Since BDNF and TrkB expression are influenced strongly by activity, we predicted that inhibitory potentiation would be diminished by manipulations that decrease central auditory activity, such as hearing loss. Two forms of hearing loss were examined: conductive hearing loss in which the cochleae are not damaged or sensorineural hearing loss in which both cochleae are removed. Both forms of hearing loss were found to reduce significantly the magnitude of inhibitory potentiation. These data indicate that early experience is necessary for the normal development of BDNF-mediated long-lasting inhibitory potentiation, which may be associated with perceptual deficits at later ages.