Spaced conditioned stimulus presentation facilitates the extinction of strong fear memory in mice.

Inducing fear memory extinction by re-presenting a conditioned stimulus (CS) is the foundation of exposure therapy for post-traumatic stress disorder (PTSD). Investigating differences in the ability of different CS presentation patterns to induce extinction learning is crucial for improving this type of therapy. Using a trace fear conditioning paradigm in mice, we demonstrate that spaced presentation of the CS facilitated the extinction of a strong fear memory to a greater extent than continuous CS presentation. These results lay the groundwork for developing more effective exposure therapy techniques for PTSD.

Rapidly-customizable, scalable 3D-printed wireless optogenetic probes for versatile applications in neuroscience.

Optogenetics is an advanced neuroscience technique that enables the dissection of neural circuitry with high spatiotemporal precision. Recent advances in materials and microfabrication techniques have enabled minimally invasive and biocompatible optical neural probes, thereby facilitating in vivo optogenetic research. However, conventional fabrication techniques rely on cleanroom facilities, which are not easily accessible and are expensive to use, making the overall manufacturing process inconvenient and costly. Moreover, the inherent time-consuming nature of current fabrication procedures impede the rapid customization of neural probes in between in vivo studies. Here, we introduce a new technique stemming from 3D printing technology for the low-cost, mass production of rapidly customizable optogenetic neural probes. We detail the 3D printing production process, on-the-fly design versatility, and biocompatibility of 3D printed optogenetic probes as well as their functional capabilities for wireless in vivo optogenetics. Successful in vivo studies with 3D printed devices highlight the reliability of this easily accessible and flexible manufacturing approach that, with advances in printing technology, can foreshadow its widespread applications in low-cost bioelectronics in the future.

Customizable, wireless and implantable neural probe design and fabrication via 3D printing.

This Protocol Extension describes the low-cost production of rapidly customizable optical neural probes for in vivo optogenetics. We detail the use of a 3D printer to fabricate minimally invasive microscale inorganic light-emitting-diode-based neural probes that can control neural circuit activity in freely behaving animals, thus extending the scope of two previously published protocols describing the fabrication and implementation of optoelectronic devices for studying intact neural systems. The 3D-printing fabrication process does not require extensive training and eliminates the need for expensive materials, specialized cleanroom facilities and time-consuming microfabrication techniques typical of conventional manufacturing processes. As a result, the design of the probes can be quickly optimized, on the basis of experimental need, reducing the cost and turnaround for customization. For example, 3D-printed probes can be customized to target multiple brain regions or scaled up for use in large animal models. This protocol comprises three procedures: (1) probe fabrication, (2) wireless module preparation and (3) implantation for in vivo assays. For experienced researchers, neural probe and wireless module fabrication requires ~2 d, while implantation should take 30-60 min per animal. Time required for behavioral assays will vary depending on the experimental design and should include at least 5 d of animal handling before implantation of the probe, to familiarize each animal to their handler, thus reducing handling stress that may influence the result of the behavioral assays. The implementation of customized probes improves the flexibility in optogenetic experimental design and increases access to wireless probes for in vivo optogenetic research.