In the big brown bat (Eptesicus fuscus), conditioning with acoustic stimuli followed by electric leg-stimulation causes shifts in frequency-tuning curves and best frequencies (hereafter BF shifts) of collicular and cortical neurons, i.e., reorganization of the cochleotopic (frequency) maps in the inferior colliculus (IC) and auditory cortex (AC). The collicular BF shift recovers 180 min after the conditioning, but the cortical BF shift lasts longer than 26 h. The collicular BF shift is not caused by conditioning, as the AC is inactivated during conditioning. Therefore it has been concluded that the collicular BF shift is caused by the corticofugal auditory system. The collicular and cortical BF shifts both are not caused by conditioning as the somatosensory cortex is inactivated during conditioning. Therefore it has been hypothesized that the cortical BF shift is mostly caused by both the subcortical (e.g., collicular) BF shift and the activity of nonauditory systems such as the somatosensory cortex excited by an unconditioned leg-stimulation and the cholinergic basal forebrain. The main aims of our present studies are to examine whether acetylcholine (ACh) applied to the AC augments the collicular and cortical BF shifts caused by the conditioning and whether atropine applied to the AC abolishes the cortical BF shift but not the collicular BF shift, as expected from the preceding hypothesis. In the awake bat, we made the following findings. ACh applied to the AC augments not only the cortical BF shift but also the collicular BF shift through the corticofugal system. Atropine applied to the AC reduces the collicular BF shift and abolishes the cortical BF shift which otherwise would be caused. ACh applied to the IC significantly augments the collicular BF shift but affects the cortical BF shift only slightly. ACh makes the cortical BF shift long-lasting beyond 4 h, but it cannot make the collicular BF shift long-lasting beyond 3 h. Atropine applied to the IC abolishes the collicular BF shift. It reduces the cortical BF shift but does not abolish it. Our findings favor the hypothesis that the BF shifts evoked by the corticofugal system, and an increased ACh level in the AC evoked by the basal forebrain are both necessary to evoke a long-lasting cortical BF shift.

SUMMARY Layer 1 (L1) of primary visual cortex (V1) is the target of projections from many brain regions outside of V1. We found that inputs to the non-columnar mouse V1 from the dorsal lateral geniculate nucleus and feedback projections from multiple higher cortical areas to L1 are patchy. The patches are matched to a pattern of M2 muscarinic acetylcholine receptor expression at fixed locations of mouse, rat and monkey V1. Neurons in L2/3 aligned with M2-rich patches have high spatial acuity whereas cells in M2-poor zones exhibited high temporal acuity. Together M2+ and M2− zones form constant-size domains that are repeated across V1. Domains map subregions of the receptive field, such that multiple copies are contained within the point image. The results suggest that the modular network in mouse V1 selects spatiotemporally distinct clusters of neurons within the point image for top-down control and differential routing of inputs to cortical streams.

The descending (corticofugal) auditory system adjusts and improves auditory signal processing in the subcortical auditory nuclei. The auditory cortex and corticofugal system evoke small, short-term changes of the subcortical auditory nuclei in response to a sound repetitively delivered to an animal. These changes are specific to the parameters characterizing the sound. When the sound becomes significant to the animal through conditioning (associative learning), the changes are augmented and the cortical changes become long-term. There are two types of reorganizations: expanded reorganization resulting from centripetal shifts in tuning curves of neurons toward the values of the parameters characterizing a sound and compressed reorganization resulting from centrifugal shifts in tuning curves of neurons away from these values. The two types of reorganizations are based on a single mechanism consisting of two components: facilitation and inhibition.

Little is known regarding differences in the gut microbiomes of rheumatoid arthritis (RA) patients and healthy cohorts in China. This study aimed to identify differences in the fecal microbiomes of 66 Chinese patients with RA and 60 healthy Chinese controls. The V3-V4 variable regions of bacterial 16S rRNA genes were sequenced with the Illumina system to define the bacterial composition. The alpha-diversity index of the microbiome of the RA patients was significantly lower than that of the control group. The bacterial genera Bacteroides (p = 0.02202) and Escherichia-Shigella (p = 0.03137) were more abundant in RA patients. In contrast, Lactobacillus (p = 0.000014), Alloprevotella (p = 0.0000008615), Enterobacter (p = 0.000005759), and Odoribacter (p = 0.0000166) were less abundant in the RA group than in the control group. Spearman correlation analysis of blood physiological measures of RA showed that bacterial genera such as Dorea and Ruminococcus were positively correlated with RF-IgA and anti-CCP antibodies. Furthermore, Alloprevotella and Parabacteroides were positively correlated with the erythrocyte sedimentation rate, and Prevotella-2 and Alloprevotella were positively correlated with C-reactive protein, both biomarkers of inflammation. These findings suggest that the gut microbiota may contribute to RA development via interactions with the host immune system.

Neocortical computations underlying vision are performed by a distributed network of functionally specialized areas. Mouse visual cortex, a dense interareal network that exhibits hierarchical properties, comprises subnetworks interconnecting distinct processing streams. To determine the layout of the mouse visual hierarchy, we have evaluated the laminar patterns formed by interareal axonal projections originating in each of ten areas. Reciprocally connected pairs of areas exhibit feedforward/feedback relationships consistent with a hierarchical organization. Beta regression analyses, which estimate a continuous hierarchical distance measure, indicate that the network comprises multiple nonhierarchical circuits embedded in a hierarchical organization of overlapping levels. Single-unit recordings in anaesthetized mice show that receptive field sizes are generally consistent with the hierarchy, with the ventral stream exhibiting a stricter hierarchy than the dorsal stream. Together, the results provide an anatomical metric for hierarchical distance, and reveal both hierarchical and nonhierarchical motifs in mouse visual cortex.