Basal ganglia (BG) circuits orchestrate complex motor behaviors predominantly via inhibitory synaptic outputs. Although these inhibitory BG outputs are known to reduce the excitability of postsynaptic target neurons, precisely how this change impairs motor performance remains poorly understood. Here, we show that optogenetic photostimulation of inhibitory BG inputs from the globus pallidus induces a surge of action potentials in the ventrolateral thalamic (VL) neurons and muscle contractions during the post-inhibitory period. Reduction of the neuronal population with this post-inhibitory rebound firing by knockout of T-type Ca channels or photoinhibition abolishes multiple motor responses induced by the inhibitory BG input. In a low dopamine state, the number of VL neurons showing post-inhibitory firing increases, while reducing the number of active VL neurons via photoinhibition of BG input, effectively prevents Parkinson disease (PD)-like motor symptoms. Thus, BG inhibitory input generates excitatory motor signals in the thalamus and, in excess, promotes PD-like motor abnormalities. VIDEO ABSTRACT.

The motor cortex orchestrates simple to complex motor behaviors through its output projections to target areas. The primary (MOp) and secondary (MOs) motor cortices are known to produce specific output projections that are targeted to both similar and different target areas. These projections are further divided into layer 5 and 6 neuronal outputs, thereby producing four cortical outputs that may target other areas in a combinatorial manner. However, the precise network structure that integrates these four projections remains poorly understood. Here, we constructed a whole-brain, three-dimensional (3D) map showing the tract pathways and targeting locations of these four motor cortical outputs in mice. Remarkably, these motor cortical projections showed unique and separate tract pathways despite targeting similar areas. Within target areas, various combinations of these four projections were defined based on specific 3D spatial patterns, reflecting anterior-posterior, dorsal-ventral, and core-capsular relationships. This 3D topographic map ultimately provides evidence for the relevance of comparative connectomics: motor cortical projections known to be convergent are actually segregated in many target areas with unique targeting patterns, a finding that has anatomical value for revealing functional subdomains that have not been classified by conventional methods.

Flexible inorganic-based micro light-emitting diodes (µLEDs) are emerging as a significant technology for flexible displays, which is an important area for bilateral visual communication in the upcoming Internet of Things era. Conventional flexible lateral µLEDs have been investigated by several researchers, but still have significant issues of power consumption, thermal stability, lifetime, and light-extraction efficiency on plastics. Here, high-performance flexible vertical GaN light-emitting diodes (LEDs) are demonstrated by silver nanowire networks and monolithic fabrication. Transparent, ultrathin GaN LED arrays adhere to a human fingernail and stably glow without any mechanical deformation. Experimental studies provide outstanding characteristics of the flexible vertical μLEDs (f-VLEDs) with high optical power (30 mW mm ), long lifetime (≈12 years), and good thermal/mechanical stability (100 000 bending/unbending cycles). The wireless light-emitting system on the human skin is successfully realized by transferring the electrical power f-VLED. Finally, the high-density GaN f-VLED arrays are inserted onto a living mouse cortex and operated without significant histological damage of brain.

Alopecia is considered an aesthetic, psychological, and social issue among modern people. Although laser-induced skin stimulation is utilized for depilation treatment, such treatment has significant drawbacks of high energy consumption, huge equipment size, and limited usage in daily life. Here, we present a wearable photostimulator for hair-growth applications using high-performance flexible red vertical light-emitting diodes (f-VLEDs). Flexible microscale LEDs were effectively fabricated by a simple monolithic fabrication process, resulting in high light output (∼30 mW mm), low forward voltage (∼2.8 V), and excellent flexibility for wearable biostimulation. Finally, trichogenic stimulation of a hairless mouse was achieved using high-performance red f-VLEDs with high thermal stability, device uniformity, and mechanical durability.

Early-life trauma (ELT) is a risk factor for binge eating and obesity later in life, yet the neural circuits that underlie this association have not been addressed. Here, we show in mice that downregulation of the leptin receptor (Lepr) in the lateral hypothalamus (LH) and its effect on neural activity is crucial in causing ELT-induced binge-like eating and obesity upon high-fat diet exposure. We also found that the increased activity of Lepr-expressing LH (LHLepr) neurons encodes sustained binge-like eating in ELT mice. Inhibition of LHLepr neurons projecting to the ventrolateral periaqueductal gray normalizes these behavioral features of ELT mice. Furthermore, activation of proenkephalin-expressing ventrolateral periaqueductal gray neurons, which receive inhibitory inputs from LHLepr neurons, rescues ELT-induced maladaptive eating habits. Our results identify a circuit pathway that mediates ELT-induced maladaptive eating and may lead to the identification of novel therapeutic targets for binge eating and obesity.