Miniature three-photon microscopy maximized for scattered fluorescence collection.

In deep-tissue multiphoton microscopy, diffusion and scattering of fluorescent photons, rather than ballistic emanation from the focal point, have been a confounding factor. Here we report on a 2.17-g miniature three-photon microscope (m3PM) with a configuration that maximizes fluorescence collection when imaging in highly scattering regimes. We demonstrate its capability by imaging calcium activity throughout the entire cortex and dorsal hippocampal CA1, up to 1.2 mm depth, at a safe laser power. It also enables the detection of sensorimotor behavior-correlated activities of layer 6 neurons in the posterior parietal cortex in freely moving mice during single-pellet reaching tasks. Thus, m3PM-empowered imaging allows the study of neural mechanisms in deep cortex and subcortical structures, like the dorsal hippocampus and dorsal striatum, in freely behaving animals.

Encoding of social novelty by sparse GABAergic neural ensembles in the prelimbic cortex.

Although the prelimbic (PrL) area is associated with social behaviors, the neural ensembles that regulate social preference toward novelty or familiarity remain unknown. Using miniature two-photon microscopy (mTPM) to visualize social behavior-associated neuronal activity within the PrL in freely behaving mice, we found that the Ca2+ transients of GABAergic neurons were more highly correlated with social behaviors than those of glutamatergic neurons. Chemogenetic suppression of social behavior-activated GABAergic neurons in the PrL disrupts social novelty behaviors. Restoring the MeCP2 level in PrL GABAergic neurons in MECP2 transgenic (MECP2-TG) mice rescues the social novelty deficits. Moreover, we identified and characterized sparsely distributed NewPNs and OldPNs of GABAergic interneurons in the PrL preferentially responsible for new and old mouse exploration, respectively. Together, we propose that social novelty information may be encoded by the responses of NewPNs and OldPNs in the PrL area, possibly via synergistic actions on both sides of the seesaw.

NREM Sleep EEG Characteristics Correlate to the Mild Cognitive Impairment in Patients with Parkinsonism.

Early identification and diagnosis of mild cognitive impairment (MCI) in patients with parkinsonism (PDS) are critical. The aim of this study was to identify biomarkers of MCI in PDS using conventional electroencephalogram (EEG) power spectral analysis and detrended fluctuation analysis (DFA). In this retrospective study, patients with PDS who underwent an overnight polysomnography (PSG) study in our hospital from 2019 to 2020 were enrolled. Patients with PDS assessed by clinical examination and questionnaires were divided into two groups: the PDS with normal cognitive function (PDS-NC) group and the PDS with MCI (PDS-MCI) group. Sleep EEG signals were extracted and purified from the PSG and subjected to a conventional power spectral analysis, as well as detrended fluctuation analysis (DFA) during wakefulness, nonrapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep. Forty patients with PDS were enrolled, including 25 with PDS-NC and 15 with PDS-MCI. Results revealed that compared with PDS-NC patients, patients with PDS-MCI had a reduced fast ratio ((alpha + beta)/(delta + theta)) and increased DFA during NREM sleep. DFA during NREM was diagnostic of PDS-MCI, with an area under the receiver operating characteristic curve of 0.753 (95% CI: 0.592-0.914) (p < 0.05). Mild cognitive dysfunction was positively correlated with NREM-DFA (r = 0.426, p = 0.007) and negatively correlated with an NREM-fast ratio (r = -0.524, p = 0.001). This suggested that altered EEG activity during NREM sleep is associated with MCI in patients with PDS. NREM sleep EEG characteristics of the power spectral analysis and DFA correlate to MCI. Slowing of EEG activity during NREM sleep may reflect contribution to the decline in NREM physiological function and is therefore a marker in patients with PDS-MCI.