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)...

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...

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...

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...

Numerous brain regions have been identified as contributing to withdrawal behaviors, but it is unclear the way in which these brain regions as a whole lead to withdrawal. The search for a final common brain pathway that is involved in withdrawal remains elusive. To address this question, we implanted osmotic minipumps containing either saline, nicotine (24 mg/kg/d), cocaine (60 mg/kg/d), or methamphetamine (4 mg/kg/d) for one week in male C57BL/6J mice. After one week, the minipumps were removed and brains collected 8 h (saline, nicotine, and cocaine) or 12 h (methamphetamine) after removal. We then performed single-cell whole-brain imaging of neural activity during the withdrawal period when brains were collected. We used hierarchical clustering and graph theory to identify similarities and differences in brain functional architecture. Although methamphetamine and cocaine shared some network similarities, the main common neuroadaptation between these psychostimulant drugs was a dramatic decrease in modula...

The hippocampus and amygdala are functionally coupled brain regions that play a crucial role in processes involving memory and learning. Because interareal communication has been reported both during specific sleep stages and in awake, behaving animals, these brain regions can serve as an archetype to establish that measuring functional interactions is important for comprehending neural systems. To this end, we analyze here a public dataset of local field potentials (LFPs) recorded in rats simultaneously from the hippocampus and amygdala during different behaviors. Employing a specific, time-lagged embedding technique, named topological causality (TC), we infer directed interactions between the LFP band powers of the two regions across six frequency bands in a time-resolved manner. The combined power and interaction signals are processed with our own unsupervised tools developed originally for the analysis of molecular dynamics simulations to effectively visualize and identify putative, neural states that ...

Time-varying pitch is a vital cue for human speech perception. Neural processing of time-varying pitch has been extensively assayed using scalp-recorded frequency-following responses (FFRs), an electrophysiological signal thought to reflect integrated phase-locked neural ensemble activity from subcortical auditory areas. Emerging evidence increasingly points to a putative contribution of auditory cortical ensembles to the scalp-recorded FFRs. However, the properties of cortical FFRs and precise characterization of laminar sources are still unclear. Here we used direct human intracortical recordings as well as extracranial and intracranial recordings from macaques and guinea pigs to characterize the properties of cortical sources of FFRs to time-varying pitch patterns. We found robust FFRs in the auditory cortex across all species. We leveraged representational similarity analysis as a translational bridge to characterize similarities between the human and animal models. Laminar recordings in animal models ...

Internal affective states produce external manifestations such as facial expressions. In humans, the Facial Action Coding System (FACS) is widely used to objectively quantify the elemental facial action units (AUs) that build complex facial expressions. A similar system has been developed for macaque monkeys—the Macaque FACS (MaqFACS); yet, unlike the human counterpart, which is already partially replaced by automatic algorithms, this system still requires labor-intensive coding. Here, we developed and implemented the first prototype for automatic MaqFACS coding. We applied the approach to the analysis of behavioral and neural data recorded from freely interacting macaque monkeys. The method achieved high performance in the recognition of six dominant AUs, generalizing between conspecific individuals ( Macaca mulatta ) and even between species ( Macaca fascicularis ). The study lays the foundation for fully automated detection of facial expressions in animals, which is crucial for investigating the neural ...