Seamless and minimally-invasive three-dimensional (3D) interpenetration of electronics within artificial or natural structures could allow for continuous monitoring and manipulation of their properties. Flexible electronics provide a means for conforming electronics to non-planar surfaces, yet targeted delivery of flexible electronics to internal regions remains difficult. Here, we overcome this challenge by demonstrating syringe injection and subsequent unfolding of submicrometer-thick, centimeter-scale macroporous mesh electronics through needles with a diameter as small as 100 micrometers. Our results show that electronic components can be injected into man-made and biological cavities, as well as dense gels and tissue, with > 90% device yield. We demonstrate several applications of syringe injectable electronics as a general approach for interpenetrating flexible electronics with 3D structures, including (i) monitoring of internal mechanical strains in polymer cavities, (ii) tight integration and low chronic immunoreactivity with several distinct regions of the brain, and (iii) in vivo multiplexed neural recording. Moreover, syringe injection enables delivery of flexible electronics through a rigid shell, delivery of large volume flexible electronics that can fill internal cavities and co-injection of electronics with other materials into host structures, opening up unique applications for flexible electronics.

Stable in vivo mapping and modulation of the same neurons and brain circuits over extended periods is critical to both neuroscience and medicine. Current electrical implants offer single-neuron spatiotemporal resolution but are limited by such factors as relative shear motion and chronic immune responses during long-term recording. To overcome these limitations, we developed a chronic in vivo recording and stimulation platform based on flexible mesh electronics, and we demonstrated stable multiplexed local field potentials and single-unit recordings in mouse brains for at least 8 months without probe repositioning. Properties of acquired signals suggest robust tracking of the same neurons over this period. This recording and stimulation platform allowed us to evoke stable single-neuron responses to chronic electrical stimulation and to carry out longitudinal studies of brain aging in freely behaving mice. Such advantages could open up future studies in mapping and modulating changes associated with learning, aging and neurodegenerative diseases.

As an important application of functional biomaterials, neural probes have contributed substantially to studying the brain. Bioinspired and biomimetic strategies have begun to be applied to the development of neural probes, although these and previous generations of probes have had structural and mechanical dissimilarities from their neuron targets that lead to neuronal loss, neuroinflammatory responses and measurement instabilities. Here we present a bioinspired design for neural probes, neuron-like electronics (NeuE), where the key building blocks mimic the subcellular structural features and mechanical properties of neurons. Full three-dimensional mapping of implanted NeuE/brain interfaces highlights the structural indistinguishability and intimate interpenetration of NeuE and neurons. Time-dependent histology and electrophysiology studies further reveal a structurally and functionally stable interface with the neuronal and glial networks shortly following implantation, thus opening opportunities for next-generation brain-machine interfaces. Finally, the NeuE subcellular structural features are shown to facilitate migration of endogenous neural progenitor cells, thus holding promise as an electrically active platform for transplantation-free regenerative medicine.

The lateral habenula (LHb) has recently emerged as a key brain region in the pathophysiology of depression. However the molecular mechanism by which LHb becomes hyperactive in depression remains unknown. Through a quantitative proteomic screen, we found that βCaMII expression was significantly upregulated in the LHb of animal models of depression, and downregulated by antidepressants. Increasing the levels of β- but not α-CamKII in the LHb strongly enhanced the synaptic efficacy and spike output of LHb neurons, and was sufficient to produce profound depressive symptoms including anhedonia and behavioral despair. Downregulation of βCaMKII levels, blocking its activity or its target molecule GluR1, reversed the depressive symptoms. These results identify βCaMKII as a powerful regulator of LHb neuron function and a key molecular determinant of depression.