CRISPR-Cas9 has been demonstrated to delete genes in postmitotic neurons. Compared to the establishment of proliferative cell lines or animal strains, it is more challenging to acquire a highly homogeneous consequence of gene editing in a stable neural network. Here we show that dCas9-based CRISPR interference (CRISPRi) can efficiently silence genes in neurons. Using a pseudotarget fishing strategy, we demonstrate that CRISPRi shows superior targeting specificity without detectable off-target activity. Furthermore, CRISPRi can achieve multiplex inactivation of genes fundamental for neurotransmitter release with high efficiency. By developing conditional CRISPRi tools targeting synaptotagmin I (Syt1), we modified the excitatory to inhibitory balance in the dentate gyrus of the mouse hippocampus and found that the dentate gyrus has distinct regulatory roles in learning and affective processes in mice. We therefore recommend CRISPRi as a useful tool for more rapid investigation of gene function in the mammalian brain.

With the recent burgeoning advances in nano-optics, ultracompact, miniaturized photonic devices with high-quality and spectacular functionalities are highly desired. Such devices’ design paradigms often call for the solution of a complex inverse nonanalytical/semianalytical problem. However, currently reported strategies dealing with amplitude-controlled meta-optics devices achieved limited functionalities mainly due to restricted search space and demanding computational schemes. Here, we established a segmented hierarchical evolutionary algorithm, aiming to solve large-pixelated, complex inverse meta-optics design and fully demonstrate the targeted performance. This paradigm allows significantly extended search space at a rapid converging speed. As typical complex proof-of-concept examples, large-pixelated meta-holograms are chosen to demonstrate the validity of our design paradigm. An improved fitness function is proposed to reinforce the performance balance among image pixels, so that the image quality is improved and computing speed is further accelerated. Broadband and full-color meta-holograms with high image fidelities using binary amplitude control are demonstrated experimentally. Our work may find important applications in the advanced design of future nanoscale high-quality optical devices.

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We present a mid-infrared (mid-IR) supercontinuum (SC) light source pumped by femtosecond pulses from a thulium doped fiber amplifier (TDFA) at 2 μm. An octave-spanning spectrum from 1.1 to 3.7 μm with an average power of 253 mW has been obtained from a single mode ZBLAN fiber. Spectral flatness of 10 dB over a 1390 nm range has been obtained in the mid-IR region from 1940 - 3330 nm. It is resulted from the enhanced self phase modulation process in femtosecond regime. The all-fiber configuration makes such broadband coherent source a compact candidate for various applications.