Whole slide scanning technology has enabled the generation of high-resolution images from complete tissue sections. However, commonly used analysis software is often unable to handle the large data files produced. Here, we present a method using the open-source software QuPath to detect, classify and quantify fluorescently-labeled cells (microglia and pericytes) in whole coronal brain tissue sections. Whole-brain sections from both male and female NG2DsRed x CX3CR1+/GFP mice were analyzed. Small regions of interest were selected and manual counts were compared with counts generated from an automated approach, across a range of detection parameters. The optimal parameters for detecting cells and classifying them as microglia or pericytes in each brain region were determined and applied to annotations corresponding to the entire somatosensory and motor cortices, hippocampus, thalamus, and hypothalamus in each section. 3.74% of all detected cells were classified as pericytes; however, this proportion was sign...

Untreated age-related hearing loss increases audiovisual integration and impacts resting state functional brain connectivity. Further, there is a relation between crossmodal plasticity and audiovisual integration strength in cochlear implant patients. However, it is currently unclear whether amplification of the auditory input by hearing aids influences audiovisual integration and resting state functional brain connectivity. We conducted a randomized controlled pilot study to investigate how the McGurk illusion, a common measure for audiovisual integration, and resting state functional brain connectivity of the auditory cortex are altered by six-month hearing aid use. Thirty-two older participants with slight-to-moderate, symmetric, age-related hearing loss were allocated to a treatment or waiting control group and measured one week before and six months after hearing aid fitting with functional magnetic resonance imaging. Our results showed a statistical trend for an increased McGurk illusion after six mo...

Tissue cryopreservation provides a convenient solution for tackling one of the major problems in neuroscience research, namely, the scarce availability of human nerve tissues, especially if needed alive. While brain tissue can be used only postmortem, live nerve tissue can reasonably well be harvested from the periphery. A valuable source of primary neurons is the intestine, which compared with brain has the advantage to be safely accessible via endoscopy. The nerve tissue innervating the intestine (the enteric nervous system; ENS) can be sampled with regular endoscopic biopsy forceps and remains viable for multiple physiological and immunohistochemical tests, as previously demonstrated. Here, we present a method to preserve, over longer periods of time, human primary neurons contained in these biopsies. The use of a cryoprotective agent and the application of controlled cooling revealed to be crucial to properly store the nerve tissue and to enable functional measurements after thawing. These primary neur...

γ Band plays a key role in the encoding of visual features in the primary visual cortex (V1). In rodents V1 two ranges within the γ band are sensitive to contrast: a broad γ band (BB) increasing with contrast, and a narrow γ band (NB), peaking at ∼60 Hz, decreasing with contrast. The functional roles of the two bands and the neural circuits originating them are not completely clear yet. Here, we show, combining experimental and simulated data, that in mice V1 (1) BB carries information about high contrast and NB about low contrast; (2) BB modulation depends on excitatory-inhibitory interplay in the cortex, while NB modulation is because of entrainment to the thalamic drive. In awake mice presented with alternating gratings, NB power progressively decreased from low to intermediate levels of contrast where it reached a plateau. Conversely, BB power was constant across low levels of contrast, but it progressively increased from intermediate to high levels of contrast. Furthermore, BB response was stronger im...

Recently developed probes for extracellular electrophysiological recordings have large numbers of electrodes on long linear shanks. Linear electrode arrays, such as Neuropixels probes, have hundreds of recording electrodes distributed over linear shanks that span several millimeters. Because of the length of the probes, linear probe recordings in rodents usually cover multiple brain areas. Typical studies collate recordings across several recording sessions and animals. Neurons recorded in different sessions and animals thus have to be aligned to each other and to a standardized brain coordinate system. Here, we evaluate two typical workflows for localization of individual electrodes in standardized coordinates. These workflows rely on imaging brains with fluorescent probe tracks and warping 3D image stacks to standardized brain atlases. One workflow is based on tissue clearing and selective plane illumination microscopy (SPIM), whereas the other workflow is based on serial block-face two-photon (SBF2P) mi...

The G2019S mutation in leucine-rich repeat kinase 2 (LRRK2) causes familial Parkinson’s disease (PD) and is also found in a subset of idiopathic cases. Prior studies in Drosophila and human induced pluripotent stem cell (iPSC)-derived dopamine neurons uncovered a pronounced effect of G2019S LRRK2 on mRNA translation. It was previously reported that G2019S LRRK2 promotes translation of mRNAs with complex 5′ untranslated region (UTR) secondary structure, resulting in increased expression of calcium channels and dysregulated calcium homeostasis in human dopamine neurons. Here, we show that dysregulated translation occurs in the brains of mammalian LRRK2 models in vivo . Through ribosome profiling studies of global translation, we observe that mRNAs with complex 5′UTR structure are also preferentially translated in the G2019S LRRK2-expressing mouse brain. Reporter assays suggest that this 5′UTR preference is independent of translation initiation factors. Conversely, translation of mRNAs with complex 5′UTR seco...

Decision-making is traditionally described as a cognitive process of deliberation followed by commitment to an action choice, preceding the planning and execution of the chosen action. However, this is challenged by recent data suggesting that during situated decisions, multiple options are specified simultaneously and compete in premotor cortical areas for selection and execution. Previous studies focused on the competition during planning and left unaddressed the dynamics of decisions during movement. Does deliberation extend into the execution phase? Are nonselected options still considered? Here we studied a decision-making task in which human participants were instructed to select a reaching path trajectory from an origin to a rectangular target, where reward was distributed nonuniformly at the target. Critically, we applied mechanical perturbations to the arm during movement to study under which conditions such perturbations produce changes of mind. Our results show that participants initially select...

The ability of the human brain to build complex expressions from simpler parts is fascinating, but the ability of the bilingual brain to do so is perhaps even more remarkable. When highly proficient bilinguals converse, they can fluidly switch from one language to another even inside sentences. Thus, they build expressions using words from more than one language. How are bilinguals able to compose words across different languages in real time? While robust evidence has implicated the left anterior temporal lobe (LATL) for the composition of words within one language, we do not know how the LATL, or other regions implicated for composition, operates when the language switches. We also do not know whether prefrontal regions associated with language control are recruited for language switching during composition. We addressed these questions with magnetoencephalography measurements in bilinguals who are fluent in two typologically distant languages, English and Korean. We observed early composition effects in...

Our lives revolve around sharing emotional stories (i.e., happy and sad stories) with other people. Such emotional communication enhances the similarity of story comprehension and neural across speaker-listener pairs. The theory of Emotions as Social Information Model (EASI) suggests that such emotional communication may influence interpersonal closeness. However, few studies have examined speaker-listener interpersonal brain synchronization (IBS) during emotional communication and whether it is associated with meaningful aspects of the speaker-listener interpersonal relationship. Here, one speaker watched emotional videos and communicated the content of the videos to 32 people as listeners (happy/sad/neutral group). Both speaker and listeners’ neural activities were recorded using EEG. After listening, we assessed the interpersonal closeness between the speaker and listeners. Compared with the sad group, sharing happy stories showed a better recall quality and a higher rating of interpersonal closeness. T...

Selective neuromodulation using designer receptors exclusively activated by designer drugs (DREADDs) has become an increasingly important research tool, as well as an emerging therapeutic approach. However, the safety profile of DREADD expression is unknown. Here, different titers of adeno-associated viral (AAV) vector were administered in an attempt to vary total expression levels of the inhibitory DREADD hM4D(Gi) in excitatory hippocampal neurons. Male Sprague Dawley rats were injected with AAV2/7 encoding DREADD-mCherry, DREADD, or mCherry. Pronounced neuronal loss and neuroinflammatory reactions were observed after transduction with the high titer DREADD AAV, which also resulted in the highest DREADD expression levels. No such effects were observed in the mCherry control group, despite an equally high titer, nor in conditions where lower viral vector titers were injected. In the high titer DREADD conditions, dentate gyrus (DG) evoked potentials were inhibited on clozapine-induced activation of hM4D(Gi)...