Light plays a pivotal role in the regulation of affective behaviors. However, the precise circuits that mediate the impact of light on depressivelike behaviors are not well understood. Here, we show that light influences depressive-like behaviors through a disynaptic circuit linking the retina and the lateral habenula (LHb). Specifically, M4type melanopsin-expressing retinal ganglion cells (RGCs) innervate GABA neurons in the thalamic ventral lateral geniculate nucleus and intergeniculate leaflet (vLGN/IGL), which in turn inhibit CaMKIIa neurons in the LHb. Specific activation of vLGN/IGL-projecting RGCs, activation of LHbprojecting vLGN/IGL neurons, or inhibition of postsynaptic LHb neurons is sufficient to decrease the depressive-like behaviors evoked by longterm exposure to aversive stimuli or chronic social defeat stress. Furthermore, we demonstrate that the antidepressive effects of light therapy require activation of the retina-vLGN/IGL-LHb pathway. These results reveal a dedicated retina-vLGN/ IGL-LHb circuit that regulates depressive-like behaviors and provide a potential mechanistic explanation for light treatment of depression.

Spinal cord injury (SCI) is considered incurable because axonal regeneration in the central nervous system (CNS) is extremely challenging, due to harsh CNS injury environment and weak intrinsic regeneration capability of CNS neurons. We discovered that neurotrophin-3 (NT3)-loaded chitosan provided an excellent microenvironment to facilitate nerve growth, new neurogenesis, and functional recovery of completely transected spinal cord in rats. To acquire mechanistic insight, we conducted a series of comprehensive transcriptome analyses of spinal cord segments at the lesion site, as well as regions immediately rostral and caudal to the lesion, over a period of 90 days after SCI. Using weighted gene coexpression network analysis (WGCNA), we established gene modules/ programs corresponding to various pathological events at different times after SCI. These objective measures of gene module expression also revealed that enhanced new neurogenesis and angiogenesis, and reduced inflammatory responses were keys to conferring the effect of NT3-chitosan on regeneration.S pinal cord injury (SCI) is a debilitating medical condition that often leads to permanent impairment of sensory and motor functions. SCI is considered almost incurable because axons in the central nervous system (CNS), unlike those in the peripheral nervous system (PNS), are believed not to regenerate. The innate ability of mature CNS neurons to regenerate is much weaker than that of PNS neurons (1). In addition, myelin debris in the injured CNS is more inhibitory toward axonal growth compared to that in the PNS (2). Moreover, the mode of immune cell infiltration and microglia activation are different in CNS versus PNS, resulting in a different cellular microenvironment, which crucially influences the outcome, i.e., PNS axons regenerate, while CNS axons do not (3).Over the years, SCI research has focused on ways to promote the long-distance growth of CNS motor axons, mainly by neutralizing inhibitory myelin components and/or changing the neuronal intrinsic program to enable better regeneration (4). Unfortunately, however, although numerous studies have been carried out following this line of strategy, no major breakthroughs translatable to therapy have been achieved. In recent years, efforts toward promoting long distance axonal growth have been complemented with alternative approaches aimed at using exogenous stem cells to generate local new neurons that form nascent relay neural networks to pass ascending and descending neurotransmission signals with or without long-distance axonal growth (5-7).SCI is a complex medical condition. The primary lesion includes the physical traumatic wounding of both white and gray matter, breakdown of the vasculature system, and acute immune reactions, which is followed by secondary lesions, such as demyelination, additional immune cell infiltration, inflammation, glial scar formation, impaired neurotransmission, and neuronal apoptosis (8). Secondary lesions are intermingled with intrinsic repair processes, including remyelina...

Animals promote their survival by avoiding rapidly approaching objects that indicate threats. In mice, looming-evoked defensive responses are triggered by the superior colliculus (SC) which receives direct retinal inputs. However, the specific neural circuits that begin in the retina and mediate this important behaviour remain unclear. Here we identify a subset of retinal ganglion cells (RGCs) that controls mouse looming-evoked defensive responses through axonal collaterals to the dorsal raphe nucleus (DRN) and SC. Looming signals transmitted by DRN-projecting RGCs activate DRN GABAergic neurons that in turn inhibit serotoninergic neurons. Moreover, activation of DRN serotoninergic neurons reduces looming-evoked defensive behaviours. Thus, a dedicated population of RGCs signals rapidly approaching visual threats and their input to the DRN controls a serotonergic self-gating mechanism that regulates innate defensive responses. Our study provides new insights into how the DRN and SC work in concert to extract and translate visual threats into defensive behavioural responses.

Exercise training has been reported to ameliorate heart dysfunction in both humans and animals after myocardial infarction (MI), but the underlying mechanisms are poorly understood. Follistatin-like1 (FSTL1) is a cardioprotective factor against ischemic injury and is induced in cardiomyocytes and skeletal muscle in ischemic and hypoxic conditions. To test the hypothesis that FSTL1 may be a molecular link between exercise and improved heart function post MI, we subjected MI-rats, induced by left coronary artery ligation, to two modes of exercise: intermittent aerobic exercise (IAE) or mechanical vibration training (MVT), for four weeks and examined the relevance of FSTL1 to exercise-mediated cardiac effects. Exercise improved the functional performance, reduced fibrosis of MI-hearts and induced FSTL1 expression, the TGFβ-Smad2/3 signaling and angiogenesis in myocardium. In gastrocnemius, exercise increased the cross-sectional area of myocytes and FSTL1 expression. Importantly, exercise increased circulating FSTL1 levels, which were positively correlated with the skeletal muscle FSTL1 expression and negatively correlated with heart fibrosis. Overall, the IAE was more effective than that of MVT in cardioprotection. Finally, exogenous FSTL1 administration directly improved angiogenesis as well as functionality of post-MI hearts. Taken together, we have demonstrated that FSTL1 is a potential mediator of exercise-induced cardioprotection in post-MI rats.

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