Highly Customizable 3D Microelectrode Arrays for In Vitro and In Vivo Neuronal Tissue Recordings.

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.

Optogenetically stimulating intact rat corticospinal tract post-stroke restores motor control through regionalized functional circuit formation.

Current neuromodulatory strategies to enhance motor recovery after stroke often target large brain areas non-specifically and without sufficient understanding of their interaction with internal repair mechanisms. Here we developed a novel therapeutic approach by specifically activating corticospinal circuitry using optogenetics after large strokes in rats. Similar to a neuronal growth-promoting immunotherapy, optogenetic stimulation together with intense, scheduled rehabilitation leads to the restoration of lost movement patterns rather than induced compensatory actions, as revealed by a computer vision-based automatic behavior analysis. Optogenetically activated corticospinal neurons promote axonal sprouting from the intact to the denervated cervical hemi-cord. Conversely, optogenetically silencing subsets of corticospinal neurons in recovered animals, results in mistargeting of the restored grasping function, thus identifying the reestablishment of specific and anatomically localized cortical microcircuits. These results provide a conceptual framework to improve established clinical techniques such as transcranial magnetic or transcranial direct current stimulation in stroke patients.