A Distributed Wireless Network of Implantable Sub-mm Cortical Microstimulators for Brain-Computer Interfaces.

Scalability of implantable neural interface devices is a critical bottleneck in enhancing the performance of cortical Brain-Computer Interfaces (BCIs) through access to high density and multi-areal cortical signals. This is challenging to achieve through current monolithic constructs with 100-200 channels, often with bulky tethering and packaging, and a spatially distributed sensor approach has recently been explored by a few groups, including our laboratories [1]. In this paper, we describe a microscale (500 µm) programmable neural stimulator in the context of an epicortical wireless networked system of sub-mm "Neurograins" with wireless energy harvesting (near 1 GHz) and bidirectional telemetry. Stimulation neurograins are post-processed to integrate poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) planar electrodes or intracortical penetrating microwires, and ensembles of microdevices are hermetically encapsulated using liquid-crystal polymer (LCP) thermocompression for chronic implantability. Radio-frequency power and telecommunications management are handled by a wearable external "Epidermal Skinpatch" unit to cater to chronic clinical implant considerations. We describe the stimulation neurograin performance specifications and proof-of-concept in bench top and ex vivo rodent platforms.

Cacna1c in the Prefrontal Cortex Regulates Depression-Related Behaviors via REDD1.

The CACNA1C gene that encodes the L-type Ca2+ channel (LTCC) Cav1.2 subunit has emerged as a candidate risk gene for multiple neuropsychiatric disorders including bipolar disorder, major depressive disorder, and schizophrenia, all marked with depression-related symptoms. Although cacna1c heterozygous (HET) mice have been previously reported to exhibit an antidepressant-like phenotype, the molecular and circuit-level dysfunction remains unknown. Here we report that viral vector-mediated deletion of cacna1c in the adult prefrontal cortex (PFC) of mice recapitulates the antidepressant-like effect observed in cacna1c HET mice using the sucrose preference test (SPT), forced swim test (FST), and tail suspension test (TST). Molecular studies identified lower levels of REDD1, a protein previously linked to depression, in the PFC of HET mice, and viral-mediated REDD1 overexpression in the PFC of these HET mice reversed the antidepressant-like effect in SPT and TST. Examination of downstream REDD1 targets found lower levels of active/phosphorylated Akt (S473) with no change in mTORC1 phosphorylation. Examination of the transcription factor FoxO3a, previously linked to depression-related behavior and shown to be regulated in other systems by Akt, revealed higher nuclear levels in the PFC of cacna1c HET mice that was further increased following REDD1-mediated reversal of the antidepressant-like phenotype. Collectively, these findings suggest that REDD1 in cacna1c HET mice may influence depression-related behavior via regulation of the FoxO3a pathway. Cacna1c HET mice thus serve as a useful mouse model to further study cacna1c-associated molecular signaling and depression-related behaviors relevant to human CACNA1C genetic variants.