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Planar microelectrode arrays (MEAs) for – in vitro or in vivo – neuronal signal recordings lack the spatial resolution and sufficient signal‐to‐noise ratio (SNR) required for a detailed understanding of neural network function and synaptic plasticity. To overcome these limitations, a highly customizable three‐dimensional (3D) printing process is used in combination with thin film technology and a self‐aligned template‐assisted electrochemical deposition process to fabricate 3D‐printed‐based MEAs on stiff or flexible substrates. Devices with design flexibility and physical robustness are shown for recording neural activity in different in vitro and in vivo applications, achieving high‐aspect ratio 3D microelectrodes of up to 33:1. Here, MEAs successfully record neural activity in 3D neuronal cultures, retinal explants, and the cortex of living mice, thereby demonstrating the versatility of the 3D MEA while maintaining high‐quality neural recordings. Customizable 3D MEAs provide unique opportunities to study neural activity under regular or various pathological conditions, both in vitro and in vivo, and contribute to the development of drug screening and neuromodulation systems that can accurately monitor the activity of large neural networks over time. Two‐photon polymerization (2PP) lithography and surface micromachining technology allow the rapid fabrication of polymer templates to guide the growth of electrodes for three‐dimensional microelectrode arrays (3D MEAs), enabling in turn, device customizability, high signal‐to‐noise ratio (SNR) recordings, low bending stiffness, and minimized cross‐sectional footprint for in vitro and in vivo neural applications: from 3D neuronal cell cultures to the cortex of living mice.

Three-dimensional (3D) microelectrode arrays (MEAs) are gaining popularity as brain-machine interfaces and platforms for studying electrophysiological activity. Interactions with neural tissue depend on the electrochemical, mechanical, and spatial features of the recording platform. While planar or protruding two-dimensional MEAs are limited in their ability to capture neural activity across layers, existing 3D platforms still require advancements in manufacturing scalability, spatial resolution, and tissue integration. In this work, we present a customizable, scalable, and straightforward approach to fabricate flexible 3D kirigami MEAs containing both surface and penetrating electrodes, designed to interact with the 3D space of neural tissue. These novel probes feature up to 512 electrodes distributed across 128 shanks in a single flexible device, with shank heights reaching up to 1 mm. We successfully deployed our 3D kirigami MEAs in several neural applications, both in vitro and in vivo, and identified spatially dependent electrophysiological activity patterns. Flexible 3D kirigami MEAs are therefore a powerful tool for large-scale electrical sampling of complex neural tissues while improving tissue integration and offering enhanced capabilities for analyzing neural disorders and disease models where high spatial resolution is required.

Propiogenic substrates and gut bacteria produce propionate, a post-translational protein modifier. In this study, we used a mouse model of propionic acidaemia (PA) to study how disturbances to propionate metabolism result in histone modifications and changes to gene expression that affect cardiac function. Plasma propionate surrogates were raised in PA mice, but female hearts manifested more profound changes in acyl-CoAs, histone propionylation and acetylation, and transcription. These resulted in moderate diastolic dysfunction with raised diastolic Ca 2+ , expanded end-systolic ventricular volume and reduced stroke volume. Propionate was traced to histone H3 propionylation and caused increased acetylation genome-wide, including at promoters of Pde9a and Mme , genes related to contractile dysfunction through downscaled cGMP signaling. The less severe phenotype in male hearts correlated with β-alanine buildup. Raising β-alanine in cultured myocytes treated with propionate reduced propionyl-CoA levels, indicating a mechanistic relationship. Thus, we linked perturbed propionate metabolism to epigenetic changes that impact cardiac function.

Field tests suggest that high-density nets can reduce harbor porpoisePhocoena phocoenaby-catch in demersal gillnet fisheries. However, it is not clear whether acoustic reflectivity or twine stiffness are responsible for this. We conducted sonar tests in a tank in the frequency range of 110 to 190 kHz and found that the target strength of the high-density BaSO₄ net was 7.2 dB higher at 150 kHz than that of the standard nylon net. In a fjord on Vancouver Island, Canada, we investigated porpoise surfacing and echolocation behavior as they encountered 2 surface gillnets (45 × 9 m, 165 mm mesh size) made of (1) standard 100% nylon and (2) a mix of BaSO₄ and nylon. The distribution of click intervals shifted to longer intervals when the BaSO₄ net was used (median = 51 ms vs. 45.2 ms for the standard net; Kolmogorov-Smirnov test, p < 0.001), indicating a greater target distance. We estimated that porpoises are able to detect BaSO₄ nets 4.4 m in advance of standard nylon nets. However, an unexpected low percentage of echolocating porpoise groups within 50 m of the center of nets (standard 30.6%, BaSO₄ 19.3%) indicates that additional measures may be necessary to reduce by-catch. A subsequent experiment showed that transmission of 2.5 kHz tones as a warning sound increased biosonar use by a factor of 4 compared to controls (16.7% for controls vs. 71.4% for groups during ensonification; chi²-test, p < 0.001). The combination of reflective nets and warning sounds may be a promising mitigative tool.

Field tests suggest that high-density nets can reduce harbor porpoise Phocoena phocoena by-catch in demersal gillnet fisheries. However, it is not clear whether acoustic reflectivity or twine stiffness are responsible for this. We conducted sonar tests in a tank in the frequency range of 110 to 190 kHz and found that the target strength of the high-density BaSO sub(4) net was 7.2 dB higher at 150 kHz than that of the standard nylon net. In a fjord on Vancouver Island, Canada, we investigated porpoise surfacing and echolocation behavior as they encountered 2 surface gillnets (45 x 9 m, 165 mm mesh size) made of (1) standard 100% nylon and (2) a mix of BaSO sub(4) and nylon. The distribution of click intervals shifted to longer intervals when the BaSO sub(4) net was used (median = 51 ms vs. 45.2 ms for the standard net; Kolmogorov-Smirnov test, p < 0.001), indicating a greater target distance. We estimated that porpoises are able to detect BaSO sub(4) nets 4.4 m in advance of standard nylon nets. However, an unexpected low percentage of echolocating porpoise groups within 50 m of the center of nets (standard 30.6%, BaSO sub(4) 19.3%) indicates that additional measures may be necessary to reduce by-catch. A subsequent experiment showed that transmission of 2.5 kHz tones as a warning sound increased biosonar use by a factor of 4 compared to controls (16.7% for controls vs. 71.4% for groups during ensonification; chi super(2)-test, p < 0.001). The combination of reflective nets and warning sounds may be a promising mitigative tool.