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Neocortical vasoactive intestinal polypeptide-expressing (VIP+) interneurons display highly diverse morpho-electrophysiological and molecular properties. To begin to understand the function of VIP+ interneurons in cortical circuits, they must be clearly and comprehensively classified into distinct subpopulations based on specific molecular markers. Here, we utilized patch-clamp RT-PCR (Patch-PCR) to simultaneously obtain the morpho-electric properties and mRNA profiles of 155 VIP+ interneurons in layers 2 and 3 (L2/3) of the mouse somatosensory cortex. Using an unsupervised clustering method, we identified 3 electrophysiological types (E-types) and 2 morphological types (M-types) of VIP+ interneurons. Joint clustering based on the combined electrophysiological and morphological features resulted in 3 morpho-electric types (ME-types). More importantly, we found these 3 ME-types expressed distinct marker genes: ~94% of Sncg+ cells were ME-type 1, 100% of Mybpc1+ cells were ME-type 2, and ~78% of Parm1+ were ME-type 3. By clarifying the properties of subpopulations of cortical L2/3 VIP+ interneurons, this study establishes a basis for future investigations aiming to elucidate their physiological roles.

Cortical interneurons can be categorized into distinct populations based on multiple modalities, including molecular signatures and morpho-electrical (M/E) properties. Recently, many transcriptomic signatures based on single-cell RNA-seq have been identified in cortical interneurons. However, whether different interneuron populations defined by transcriptomic signature expressions correspond to distinct M/E subtypes is still unknown. Here, we applied the Patch-PCR approach to simultaneously obtain the M/E properties and messenger RNA (mRNA) expression of600 interneurons in layer V of the mouse somatosensory cortex (S1). Subsequently, we identified 11 M/E subtypes, 9 neurochemical cell populations (NCs), and 20 transcriptomic cell populations (TCs) in this cortical lamina. Further analysis revealed that cells in many NCs and TCs comprised several M/E types and were difficult to clearly distinguish morpho-electrically. A similar analysis of layer V interneurons of mouse primary visual cortex (V1) and motor cortex (M1) gave results largely comparable to S1. Comparison between S1, V1, and M1 suggested that, compared to V1, S1 interneurons were morpho-electrically more similar to M1. Our study reveals the presence of substantial M/E variations in cortical interneuron populations defined by molecular expression.

Cortical GABAergic interneurons can be categorized into distinct subtypes based on multiple modalities, however, it remains unclear to what extent these modalities are correlated. Here, we utilized patch-clamp RT-PCR (Patch-PCR) to simultaneously obtain the morpho-electric properties and mRNA profiles of over 600 interneurons (374 were morphologically reconstructed) in layer 5 of the mouse somatosensory cortex, based on which we identified 11 morpho-electric types (M/E-types), 9 neurochemical types (NC-types) and 20 transcriptomic types (T-types). We found that most NC-types comprised multiple M/E-types. While some M/E-types preferentially expressed specific transcriptomic signatures, a clear one-to-one correspondence between M/E-types and T-types was rarely observed. Moreover, we found that most M/E-types were distributed in a specific sub-lamina of cortical layer 5 and derived from dedicated embryonic origins. These results provide a systematic framework linking distinctive gene expression and phenotypic characterization of interneurons in a specific cortical layer.

A small subset of interneurons that are generated earliest as pioneer neurons are the first cohort of neurons that enter the neocortex. However, it remains largely unclear whether these early-generated interneurons (EGIns) predominantly regulate neocortical circuit formation. Using inducible genetic fate mapping to selectively labeled EGIns and pseudo-random interneurons (pRIns), we found that EGIns exhibited more mature electrophysiological and morphological properties and higher synaptic connectivity than pRIns at early postnatal stages. In addition, when stimulating one cell, the proportion of EGIns that influence spontaneous network synchronization is significantly higher than that of pRIns. Importantly, toxin-mediated ablation of EGIns after birth significantly reduce spontaneous network synchronization and decrease inhibitory synaptic transmission during the first postnatal week. These results suggest that EGIns can shape developing networks and may contribute to the refinement of neuronal connectivity before the establishment of the adult neuronal circuit.

In some applications, especially for the attitude control of navigation system, the friction moment of instrument ball bearings is one of the much more important factors. Its magnitude and fluctuation affect not only the energy transfer but also the accuracy of signal transfer even though the bearings work at very low speed. Experimental analysis showed that the cage rotated with a minor fluctuation along its orbital axis and even this minor fluctuation could also make a great contribution to the moment for the ball bearing. A simplified model of deformation within the contact of ball and cage was built to deduce the contact time. Combined with the experimental results, the angular acceleration were obtained by the model of contact, then the value of moment due to sliding, which induced the fluctuation of cage, between ball and ribbon cage pockets of miniature bearing were obtained.