Optogenetics has revolutionized the experimental interrogation of neural circuits and holds promise for the treatment of neurological disorders. It is limited, however, because visible light cannot penetrate deep inside brain tissue. Upconversion nanoparticles (UCNPs) absorb tissue-penetrating near-infrared (NIR) light and emit wavelength-specific visible light. Here, we demonstrate that molecularly tailored UCNPs can serve as optogenetic actuators of transcranial NIR light to stimulate deep brain neurons. Transcranial NIR UCNP-mediated optogenetics evoked dopamine release from genetically tagged neurons in the ventral tegmental area, induced brain oscillations through activation of inhibitory neurons in the medial septum, silenced seizure by inhibition of hippocampal excitatory cells, and triggered memory recall. UCNP technology will enable less-invasive optical neuronal activity manipulation with the potential for remote therapy.

The ability to recognize information incongruous with previous experience is critical for survival, thus novelty signals in the mammalian brain have evolved to enhance attention, perception and memory 1-3 . Although the importance of regions such as the ventral tegmental area 4-6 and locus coeruleus 6,7 in broadly signaling novelty has been well established, these diffuse monoaminergic transmitters have yet to be shown to convey specific information regarding the type of stimuli that drive them 6 . Whether distinct types of novelty, such as contextual and social novelty, are differently processed and routed in the brain remain unclear. Here we identify a novelty hub in the hypothalamus -the supramammillary nucleus (SuM) 8 . Unique about this region is that it not only responds broadly to novel stimuli, but segregates and selectively routes different types of information to discrete cortical targets, the dentate gyrus (DG) and CA2 fields of the hippocampus, for the modulation of mnemonic processing. Taking advantage of a novel SuM-Cre transgenic mouse, we found that DG-projecting SuM neurons are activated by contextual novelty while the SuM-CA2 circuit is preferentially activated by novel social encounters. Circuitbased manipulation demonstrated that divergent novelty channeling in these projections significantly modifies hippocampal-based contextual or social memory. This content-

Understanding information processing in the brain requires us to monitor neural activity at high spatiotemporal resolution. Using an ultrafast two-photon fluorescence microscope (2PFM) empowered by all-optical laser scanning, we imaged neural activity in vivo at up to 3,000 frames per second and submicron spatial resolution. This ultrafast imaging method enabled monitoring of both supra- and sub-threshold electrical activity down to 345 μm below the brain surface in head-fixed awake mice.

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Polar interactions such as electrostatic forces and hydrogen bonds play an essential role in biological molecular recognition. On a protein surface, polar interactions occur mostly in a hydrophobic environment because nonpolar amino acid residues cover ~75% of the protein surface. We report that ionic interactions on a hydrophobic surface are modulated by their subnanoscale distance to the surface. We developed a series of ionic head groups-appended self-assembled monolayers with C2, C6, C8, and C12 space-filling alkyl chains, which capture a dendritic guest via the formation of multiple salt bridges. The guest release upon protonolysis is progressively suppressed when its distance from the background hydrophobe changes from 1.2 (C2) to 0.2 (C12) nanometers, with an increase in salt bridge strength of ~3.9 kilocalories per mole.

An accumulating body of experimental evidence has implicated hippocampal replay occurring within sharp wave ripples (SPW-Rs) as crucial for learning and memory in healthy subjects. This raises speculation that neurological disorders impairing memory disrupt either SPW-Rs or their underlying neuronal activity. We report that mice heterozygous for the gene Scn2a, a site of frequent de novo mutations in humans with intellectual disability, displayed impaired spatial memory. While we observed no changes during encoding, to either single place cells or cell assemblies, we identified abnormalities restricted to SPW-R episodes that manifest as decreased cell assembly reactivation strengths and truncated hippocampal replay sequences. Our results suggest that alterations to hippocampal replay content may underlie disease-associated memory deficits.

Considering the existing issues of traditional blood pressure (BP) measurement methods and non-invasive continuous BP measurement techniques, this study aims to establish the systolic BP and diastolic BP estimation models based on machine learning using pulse transit time and characteristics of pulse waveform. In the process of model construction, the mean impact value method was introduced to investigate the impact of each feature on the models and the genetic algorithm was introduced to implement parameter optimization. The experimental results showed that the proposed models could effectively describe the nonlinear relationship between the features and BP and had higher accuracy than the traditional methods with the error of 3.27 ± 5.52 mmHg for systolic BP and 1.16 ± 1.97 mmHg for diastolic BP. Moreover, the estimation errors met the requirements of the Advancement of Medical Instrumentation and British Hypertension Society criteria. In conclusion, this study was helpful in promoting the practical application of methods for non-invasive continuous BP estimation models.

Inadequate sleep is a prevalent problem within our society that can result in cognitive dysfunction. Elevations in kynurenic acid (KYNA), a metabolite of the kynurenine pathway (KP) of tryptophan degradation known to impact cognition, in the brain may constitute a molecular link between sleep loss and cognitive impairment. To test this hypothesis, we investigated the impact of 6 hours of sleep deprivation on memory and KP metabolism (brain and plasma) in male and female rats. Sleep-deprived males were impaired in a contextual memory paradigm, and both sexes were impaired in a recognition memory paradigm. After sleep deprivation, hippocampal KYNA levels increased significantly only in males. The response in hippocampal KYNA levels to sleep loss was suppressed in gonadectomized males, delineating a role of circulating gonadal hormones. Circulating corticosterone, which has previously been linked to KP metabolism, correlated negatively with hippocampal KYNA in sleep-deprived females, however the relationship was not significant in male animals. Taken together, our study introduces striking sex differences in brain KYNA formation and circulating corticosterone in response to sleep deprivation. Relating these findings to sex differences in cognitive outcomes after sleep deprivation may further advance the development of novel therapeutic agents to overcome sleep loss-induced cognitive dysfunction.