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Light adaptation enables the vertebrate visual system to operate over a wide range of ambient illumination. Regulation of phototransduction in photoreceptors is considered a major mechanism underlying light adaptation. However, various types of neurons and glial cells exist in the retina, and whether and how all retinal cells interact to adapt to light/dark conditions at the cellular and molecular levels requires systematic investigation. Therefore, we utilized single-cell RNA sequencing to dissect retinal cell-type-specific transcriptomes during light/dark adaptation in mice. The results demonstrated that, in addition to photoreceptors, other retinal cell types also showed dynamic molecular changes and specifically enriched signaling pathways under light/dark adaptation. Importantly, Müller glial cells (MGs) were identified as hub cells for intercellular interactions, displaying complex cell‒cell communication with other retinal cells. Furthermore, light increased the transcription of the deiodinase Dio2 in MGs, which converted thyroxine (T4) to active triiodothyronine (T3). Subsequently, light increased T3 levels and regulated mitochondrial respiration in retinal cells in response to light conditions. As cones specifically express the thyroid hormone receptor Thrb, they responded to the increase in T3 by adjusting light responsiveness. Loss of the expression of Dio2 specifically in MGs decreased the light responsive ability of cones. These results suggest that retinal cells display global transcriptional changes under light/dark adaptation and that MGs coordinate intercellular communication during light/dark adaptation via thyroid hormone signaling. [ABSTRACT FROM AUTHOR]

Objectives: Higher static magnetic field (SMF) enables higher imaging capability in magnetic resonance imaging (MRI), which encourages the development of ultra-high field MRIs above 20 T with a prerequisite for safety issues. However, animal tests of ≥ 20 T SMF exposure are very limited. The objective of the current study is to evaluate mice behaviour consequences of 3.5–23.0 T SMF exposure. Methods: We systematically examined 112 mice for their short- and long-term behaviour responses to a 2-h exposure of 3.5–23.0 T SMFs. Locomotor activity and cognitive functions were measured by five behaviour tests, including balance beam, open field, elevated plus maze, three-chamber social recognition, and Morris water maze tests. Results: Besides the transient short-term impairment of the sense of balance and locomotor activity, the 3.5–23.0 T SMFs did not have long-term negative effects on mice locomotion, anxiety level, social behaviour, or memory. In contrast, we observed anxiolytic effects and positive effects on social and spatial memory of SMFs, which is likely correlated with the significantly increased CaMKII level in the hippocampus region of high SMF-treated mice. Conclusions: Our study showed that the short exposures to high-field SMFs up to 23.0 T have negligible side effects on healthy mice and may even have beneficial outcomes in mice mood and memory, which is pertinent to the future medical application of ultra-high field SMFs in MRIs and beyond. Key Points: • Short-term exposure to magnetic fields up to 23.0 T is safe for mice. • High-field static magnetic field exposure transiently reduced mice locomotion. • High-field static magnetic field enhances memory while reduces the anxiety level. [ABSTRACT FROM AUTHOR]

Retinal organoids (ROs) derived from human inducible pluripotent stem cells (hiPSCs) exhibit considerable therapeutic potential. However, current quality control of ROs during in vitro differentiation is largely limited to the detection of molecular markers, often by immunostaining, polymerase chain reaction (PCR) assays and sequencing, often without proper functional assessments. As such, in the current study, we systemically characterized the physiological maturation of photoreceptor‐like cells in hiPSC‐derived ROs. By performing patch‐clamp recordings from photoreceptor‐like cells in ROs at distinct differentiation stages (ie, Differentiation Day [D]90, D150, and D200), we determined the electrophysiological properties of the plasma membrane and several characteristic ion channels closely associated with the physiological functions of the photoreceptors. Ionic hallmarks, such as hyperpolarization‐activated cyclic nucleotide‐gated (HCN) channels and cyclic nucleotide‐gated (CNG) channels, matured progressively during differentiation. After D200 in culture, these characteristic currents closely resembled those in macaque or human native photoreceptors. Furthermore, we demonstrated that the hyperpolarization‐activated inward current/depolarization‐activated outward current ratio (I−120/I+40), termed as the inward‐outward current (IOC) ratio hereon, accurately represented the maturity of photoreceptors and could serve as a sensitive indicator of pathological state. Thus, this study provides a comprehensive dataset describing the electrophysiological maturation of photoreceptor‐like cells in hiPSC‐derived ROs for precise and sensitive quality control during RO differentiation. [ABSTRACT FROM AUTHOR]

Studies reported that quantum dots (QDs), as a novel probe, demonstrated a promising future for in vivo imaging, but also showed potential toxicity. This study is mainly to investigate in vivo response in the central nervous system (CNS) after exposure to QDs in a rat model of synaptic plasticity and spatial memory. Adult rats were exposed to streptavidin-conjugated CdSe/ZnS QDs (Qdots 525, purchased from Molecular Probes Inc.) by intraperitoneal injection for 7 days, followed by behavioral, electrophysiological, and biochemical examinations. The electrophysiological results show that input/output ( I/ O) functions were increased, while the peak of paired-pulse reaction and long-term potentiation were decreased after QDs insult, indicating synaptic transmission was enhanced and synaptic plasticity in the hippocampus was impaired. Meanwhile, behavioral experiments provide the evidence that QDs could impair rats' spatial memory process. All the results present evidences of interference of synaptic transmission and plasticity in rat hippocampal dentate gyrus area by QDs insult and suggest potential adverse issues which should be considered in QDs applications. [ABSTRACT FROM AUTHOR]

With the increasing applications of titanium dioxide nanoparticles (TiO NPs) in industry and daily life, an increasing number of studies showed that TiO NPs may have negative effects on the respiratory or metabolic circle systems of organisms, while very few studies focused on the brain central nervous system (CNS). Synaptic plasticity in hippocampus is believed to be associated with certain high functions of CNS, such as learning and memory. Thus, in this study, we investigated the effects of developmental exposure to TiO NPs on synaptic plasticity in rats' hippocampal dentate gyrus (DG) area using in vivo electrophysiological recordings. The input/output ( I/ O) functions, paired-pulse reaction (PPR), field excitatory postsynaptic potential, and population spike amplitude were measured. The results showed that the I/ O functions, PPR, and long-term potentiation were all attenuated in lactation TiO NPs-exposed offspring rats compared with those in the control group. However, in the pregnancy TiO NPs exposure group, only PPR was attenuated significantly. These findings suggest that developmental exposure to TiO NPs could affect synaptic plasticity in offspring's hippocampal DG area in vivo, which indicates that developmental brains, especially in lactation, are susceptible to TiO NPs exposure. This study reveals the potential toxicity of TiO NPs in CNS. It may give some hints on the security of TiO NPs production and application and shed light on its future toxicological studies. [ABSTRACT FROM AUTHOR]

Ghrelin, an orexigenic hormone, is mainly produced by the stomach and released into the circulation. Ghrelin receptors (growth hormone secretagogue receptors) are expressed throughout the brain, including the hippocampus. The activation of ghrelin receptors facilitates high-frequency stimulation (HFS)-induced long-term potentiation (LTP) in vitro, and also improves learning and memory. Herein, we report that a single infusion of ghrelin into the hippocampus led to long-lasting potentiation of excitatory postsynaptic potentials (EPSPs) and population spikes (PSs) in the dentate gyrus of anesthetized rats. This potentiation was accompanied by a reduction in paired-pulse depression of the EPSP slope, an increase in paired-pulse facilitation of the PS amplitude, and an enhancement of EPSP-spike coupling, suggesting the involvement of both presynaptic and postsynaptic mechanisms. Meanwhile, ghrelin infusion time-dependently increased the phosphorylation of Akt-Ser473, a downstream molecule of phosphoinositide 3-kinase (PI3K). Interestingly, PI3K inhibitors, but not NMDA receptor antagonist, inhibited ghrelin-induced potentiation. Although ghrelin had no effect on the induction of HFS-induced LTP, it prolonged the expression of HFS-induced LTP through extracellular signal-regulated kinase (ERK)1/2. The Morris water maze test showed that ghrelin enhanced spatial memory, and that this was prevented by pretreatment with PI3K inhibitor. Taken together, the findings show that: (i) a single infusion of ghrelin induced a new form of synaptic plasticity by activating the PI3K signaling pathway, without HFS and NMDA receptor activation; (ii) a single infusion of ghrelin also enhanced the maintenance of HFS-induced LTP through ERK activation; and (iii) repetitive infusion of ghrelin enhanced spatial memory by activating the PI3K signaling pathway. Thus, we propose that the ghrelin signaling pathway could have therapeutic value in cognitive deficits. [ABSTRACT FROM AUTHOR]