Dynamic switching of neural oscillations in the prefrontal-amygdala circuit for naturalistic freeze-or-flight.

The medial prefrontal cortex (mPFC) and basolateral amygdala (BLA) are involved in the regulation of defensive behavior under threat, but their engagement in flexible behavior shifts remains unclear. Here, we report the oscillatory activities of mPFC-BLA circuit in reaction to a naturalistic threat, created by a predatory robot in mice. Specifically, we found dynamic frequency tuning among two different theta rhythms (~5 or ~10 Hz) was accompanied by agile changes of two different defensive behaviors (freeze-or-flight). By analyzing flight trajectories, we also found that high beta (~30 Hz) is engaged in the top-down process for goal-directed flights and accompanied by a reduction in fast gamma (60 to 120 Hz, peak near 70 Hz). The elevated beta nested the fast gamma activity by its phase more strongly. Our results suggest that the mPFC-BLA circuit has a potential role in oscillatory gear shifting allowing flexible information routing for behavior switches.

Haploinsufficiency of Cyfip2 Causes Lithium-Responsive Prefrontal Dysfunction.

OBJECTIVE: Genetic variants of the cytoplasmic FMR1-interacting protein 2 (CYFIP2) encoding an actin-regulatory protein are associated with brain disorders, including intellectual disability and epilepsy. However, specific in vivo neuronal defects and potential treatments for CYFIP2-associated brain disorders remain largely unknown. Here, we characterized Cyfip2 heterozygous (Cyfip2+/- ) mice to understand their neurobehavioral phenotypes and the underlying pathological mechanisms. Furthermore, we examined a potential treatment for such phenotypes of the Cyfip2+/- mice and specified a neuronal function mediating its efficacy. METHODS: We performed behavioral analyses of Cyfip2+/- mice. We combined molecular, ultrastructural, and in vitro and in vivo electrophysiological analyses of Cyfip2+/- prefrontal neurons. We also selectively reduced CYFIP2 in the prefrontal cortex (PFC) of mice with virus injections. RESULTS: Adult Cyfip2+/- mice exhibited lithium-responsive abnormal behaviors. We found increased filamentous actin, enlarged dendritic spines, and enhanced excitatory synaptic transmission and excitability in the adult Cyfip2+/- PFC that was restricted to layer 5 (L5) neurons. Consistently, adult Cyfip2+/- mice showed increased seizure susceptibility and auditory steady-state responses from the cortical electroencephalographic recordings. Among the identified prefrontal defects, lithium selectively normalized the hyperexcitability of Cyfip2+/- L5 neurons. RNA sequencing revealed reduced expression of potassium channel genes in the adult Cyfip2+/- PFC. Virus-mediated reduction of CYFIP2 in the PFC was sufficient to induce L5 hyperexcitability and lithium-responsive abnormal behavior. INTERPRETATION: These results suggest that L5-specific prefrontal dysfunction, especially hyperexcitability, underlies both the pathophysiology and the lithium-mediated amelioration of neurobehavioral phenotypes in adult Cyfip2+/- mice, which can be implicated in CYFIP2-associated brain disorders. ANN NEUROL 2020;88:526-543.

Differential modulation of global and local neural oscillations in REM sleep by homeostatic sleep regulation.

Homeostatic rebound in rapid eye movement (REM) sleep normally occurs after acute sleep deprivation, but REM sleep rebound settles on a persistently elevated level despite continued accumulation of REM sleep debt during chronic sleep restriction (CSR). Using high-density EEG in mice, we studied how this pattern of global regulation is implemented in cortical regions with different functions and network architectures. We found that across all areas, slow oscillations repeated the behavioral pattern of persistent enhancement during CSR, whereas high-frequency oscillations showed progressive increases. This pattern followed a common rule despite marked topographic differences. The findings suggest that REM sleep slow oscillations may translate top-down homeostatic control to widely separated brain regions whereas fast oscillations synchronizing local neuronal ensembles escape this global command. These patterns of EEG oscillation changes are interpreted to reconcile two prevailing theories of the function of sleep, synaptic homeostasis and sleep dependent memory consolidation.

A Comprehensive Evaluation of the Process of Copying a Complex Figure in Early- and Late-Onset Alzheimer Disease: A Quantitative Analysis of Digital Pen Data.

BACKGROUND: The Rey-Osterrieth Complex Figure Test (RCFT) is a neuropsychological test that is widely used to assess visual memory and visuoconstructional deficits in patients with cognitive impairment, including Alzheimer disease (AD). Patients with AD have an increased tendency for exhibiting extraordinary behaviors in the RCFT for selecting the drawing area, organizing the figure, and deciding the order of images, among other activities. However, the conventional scoring system based on pen and paper has a limited ability to reflect these detailed behaviors. OBJECTIVE: This study aims to establish a scoring system that addresses not only the spatial arrangement of the finished drawing but also the drawing process of patients with AD by using digital pen data. METHODS: A digital pen and tablet were used to copy complex figures. The stroke patterns and kinetics of normal controls (NCs) and patients with early-onset AD (EOAD) and late-onset AD (LOAD) were analyzed by comparing the pen tip trajectory, spatial arrangement, and similarity of the finished drawings. RESULTS: Patients with AD copied the figure in a more fragmented way with a longer pause than NCs (EOAD: P=.045; LOAD: P=.01). Patients with AD showed an increased tendency to draw the figures closer toward the target image in comparison with the NCs (EOAD: P=.005; LOAD: P=.01) Patients with AD showed the lower accuracy than NCs (EOAD: P=.004; LOAD: P=.002). Patients with EOAD and LOAD showed similar but slightly different drawing behaviors, especially in space use and in the initial stage of drawing. CONCLUSIONS: The digitalized complex figure test evaluated copying performance quantitatively and further elucidated the patients' ongoing process during copying. We believe that this novel approach can be used as a digital biomarker of AD. In addition, the repeatability of the test will delineate the process of executive functions and constructional organization abilities with disease progression.

Galectin-1 from conditioned medium of three-dimensional culture of adipose-derived stem cells accelerates migration and proliferation of human keratinocytes and fibroblasts.

Keratinocytes and fibroblasts cells play important roles in the skin-wound healing process and are the cell types activated by trauma. Activated cells participate in epithelialization, granulation, scar tissue formation, wound remodeling, and angiogenesis via a series of cellular activities including migration and proliferation. Previous studies reported that the conditioned medium (CM) of adipose-derived stem cells (ADSCs) stimulated the migration and proliferation of cell types involved in the skin wound healing process; however, these studies only show ADSC-CM effects that were obtained using 2-dimensional (2D) culture. Recently, 3-dimensional (3D) culture has been considered as a more physiologically appropriate system than 2D culture for ADSC cultures; therefore, ADSC-CM was collected from 3D culture (ADSC-CM-3D) and compared with ADSC-CM from 2D culture (ADSC-CM-2D) to investigate the effects on the migration and proliferation of human keratinocytes (HaCaTs) and fibroblasts. The migrations of the HaCaT cells and fibroblasts were significantly higher with ADSC-CM-3D compared with the 2D culture; similarly, the proliferation of HaCaT cells was also highly stimulated by ADSC-CM-3D. Proteomic analyses of the ADSC-CM revealed that collagens and actins were highly expressed in the 3D-culture system. Chitinase 3-like 1 (CHI3L1), tissue inhibitor of metalloproteinases (TIMP), and galectin-1 were specifically expressed only in ADSC-CM-3D. Especially, through antibody neutralization, galectin-1 in ADSC-CM-3D was found to be an important factor for the migration of human keratinocytes. Therefore, these results suggest that ADSC-CM-3D was more effective in the wound healing than ADSC-CM-2D, and galectin-1 in ADSC-CM-3D was could be a promising option for skin-wound healing. Furthermore, the differential expressions of several ADSC-CM proteins between the 2D- and 3D-culture systems may be used as basic information for the development of efficient wound-healing strategies.

Cortically projecting basal forebrain parvalbumin neurons regulate cortical gamma band oscillations.

Cortical gamma band oscillations (GBO, 30-80 Hz, typically ∼40 Hz) are involved in higher cognitive functions such as feature binding, attention, and working memory. GBO abnormalities are a feature of several neuropsychiatric disorders associated with dysfunction of cortical fast-spiking interneurons containing the calcium-binding protein parvalbumin (PV). GBO vary according to the state of arousal, are modulated by attention, and are correlated with conscious awareness. However, the subcortical cell types underlying the state-dependent control of GBO are not well understood. Here we tested the role of one cell type in the wakefulness-promoting basal forebrain (BF) region, cortically projecting GABAergic neurons containing PV, whose virally transduced fibers we found apposed cortical PV interneurons involved in generating GBO. Optogenetic stimulation of BF PV neurons in mice preferentially increased cortical GBO power by entraining a cortical oscillator with a resonant frequency of ∼40 Hz, as revealed by analysis of both rhythmic and nonrhythmic BF PV stimulation. Selective saporin lesions of BF cholinergic neurons did not alter the enhancement of cortical GBO power induced by BF PV stimulation. Importantly, bilateral optogenetic inhibition of BF PV neurons decreased the power of the 40-Hz auditory steady-state response, a read-out of the ability of the cortex to generate GBO used in clinical studies. Our results are surprising and novel in indicating that this presumptively inhibitory BF PV input controls cortical GBO, likely by synchronizing the activity of cortical PV interneurons. BF PV neurons may represent a previously unidentified therapeutic target to treat disorders involving abnormal GBO, such as schizophrenia.

Localized surface plasmon resonance-based label-free biosensor for highly sensitive detection of dopamine.

Localized surface plasmon resonance (LSPR) is the phenomenon that is observed on specific metal nanoparticles (NPs) like Au, Ag which can be used for sensitive detection for many kinds of biomaterials. Dopamine (DA) is a typical neurotransmitter considered as indicator of some neural diseases. Due to its small size, it is very difficult to detect DA at low concentrations directly and sensitively with conventional sensing techniques. In this research, we propose a DA detection sensor based on LSPR phenomenon. Electrochemical deposition technique was used to make LSPR substrates, where Au NPs were electrochemically deposited on ITO glasses and these substrates showed optical characteristic of LSPR phenomenon. Different concentrations of DA solution were deposited on antibody immobilized LSPR substrates. With additions of increasing concentrations of DA, LSPR peak intensity was increased linearly. These results could be applied to many fields of clinical trials for diseases caused by small molecules.

Synergistic effect of interleukin-6 and hyaluronic acid on cell migration and ERK activation in human keratinocytes.

Wound healing is initiated and progressed by complex integrated process of cellular, physiologic, and biochemical events, such as inflammation, cell migration and proliferation. Interleukin 6 (IL-6) is a multifunctional cytokine, and it could regulate the inflammatory response of wound healing process in a timely manner. Hyaluronic acid (HA) is an essential component of the extracellular matrix, and contributes significantly to cell proliferation and migration. The purpose of this study was to investigate the effects of IL-6 or/and HA on the cell migration process in human keratinocytes. Combining IL-6 and HA significantly increased the cell migration in scratch based wound healing assay. The phosphorylation of extracellular-signal-regulated kinase (ERK) was significantly increased after 1 hr of IL-6 and HA treatment, but the phosphorylation of p38 mitogen-activated protein kinase (MAPK) was not. We also found that significant increase of the NF-κB translocation from cytoplasm into nucleus after 1 hr of IL-6 or/and HA treatments. This study firstly showed that synergistic effects of combining IL-6 and HA on the cell migration of wound healing by activation of ERK and NF-κB signaling. Further studies might be required to confirm the synergistic effects of HA and IL-6 in the animal model for the development of a novel therapeutic mixture for stimulation of wound healing process.

Simultaneous two-photon imaging and wireless EEG recording in mice.

Background: In vivo two-photon imaging is a reliable method with high spatial resolution that allows observation of individual neuron and dendritic activity longitudinally. Neurons in local brain regions can be influenced by global brain states such as levels of arousal and attention that change over relatively short time scales, such as minutes. As such, the scientific rigor of investigating regional neuronal activities could be enhanced by considering the global brain state. New method: In order to assess the global brain state during in vivo two-photon imaging, CBRAIN (collective brain research platform aided by illuminating neural activity), a wireless EEG collecting and labeling device, was controlled by the same computer of two-photon microscope. In an experiment to explore neuronal responses to isoflurane anesthesia through two-photon imaging, we investigated whether the response of individual cells correlated with concurrent EEG changes induced by anesthesia. Results: In two-photon imaging, calcium activities of the excitatory neurons in the primary somatosensory cortex disappeared in about 30s after to the initiation of isoflurane anesthesia. The simultaneously recorded EEG showed various transitional activity for about 7 min from the initiation of anesthesia and continued with burst and suppression alternating pattern thereafter. As such, there was a dissociation between excitatory neuron activity of the primary somatosensory cortex and the global brain activity under anesthesia. Comparison with existing methods: Existing methods to combine two-photon and EEG recording used wired EEG recording. In this study, wireless EEG was used in conjunction with two-photon imaging, facilitated by CBRAIN. More importantly, built-in algorithms of the CBRAIN can automatically detect brain state such as sleep. The codes used for EEG classification are easy to use, with no prior experience required. Conclusion: Simultaneous recording of wireless EEG and two-photon imaging provides a practical way to capture individual neuronal activities with respect to global brain state in an experimental set-up.

Social context modulates multibrain broadband dynamics and functional brain-to-brain coupling in the group of mice.

Although mice are social, multiple animals' neural activities are rarely explored. To characterise the neural activities during multi-brain interaction, we simultaneously recorded local field potentials (LFP) in the prefrontal cortex of four mice. The social context and locomotive states predominately modulated the entire LFP structure. The power of lower frequency bands-delta to alpha-were correlated with each other and anti-correlated with gamma power. The high-to-low-power ratio (HLR) provided a useful measure to understand LFP changes along the change of behavioural and locomotive states. The HLR during huddled conditions was lower than that during non-huddled conditions, dividing the social context into two. Multi-brain analyses of HLR indicated that the mice in the group displayed high cross-correlation. The mice in the group often showed unilateral precedence of HLR by Granger causality analysis, possibly comprising a hierarchical social structure. Overall, this study shows the importance of the social environment in brain dynamics and emphasises the simultaneous multi-brain recordings in social neuroscience.

Hairless plays a role in formation of inner root sheath via regulation of Dlx3 gene.

The Hairless (Hr), a transcription factor, is expressed in the suprabasal cell layer of the interfollicular epidermis and the lower portion of the hair follicle epithelium, where its expression is dependent on the hair cycle. Recently, we reported a new Hr mutant mouse, Hr(Hp), in which the hairless protein (HR) was overexpressed. In this study, we documented abnormal formation of inner root sheath (IRS), suppressed expression of Dlx3, and IRS keratins in the Hr(Hp)/Hr(Hp) skin. We also found that HR down-regulated Dlx3 mRNA expression through suppression of Dlx3 promoter activity. In addition, we showed that Dlx3 regulated the expression of IRS keratins. Our results demonstrate that regulation of Dlx3 by HR affects the IRS keratin expression, thus modulating the formation of IRS of hair follicle.

Single nucleotide deletion mutation of KCNH2 gene is responsible for LQT syndrome in a 3-generation Korean family.

Long QT syndrome (LQTS) is characterized by the prolongation of the QT interval in ECG and manifests predisposition to life threatening arrhythmia which often leads to sudden cardiac death. We encountered a 3-generation family with 5 affected family members in which LQTS was inherited in autosomal dominant manner. The LQTS is considered an ion channel disorder in which the type and location of the genetic mutation determines to a large extent the expression of the clinical syndrome. Upon screening of the genomic sequences of cardiac potassium ion channel genes, we found a single nucleotide C deletion mutation in the exon 3 of KCNH2 gene that co-segregates with the LQTS in this family. This mutation presumably resulted in a frameshift mutation, P151fs+15X. This study added a new genetic cause to the pool of mutations that lead to defected potassium ion channels in the heart.

A guide towards optimal detection of transient oscillatory bursts with unknown parameters.

Objectives. Recent event-based analyses of transient neural activities have characterized the oscillatory bursts as a neural signature that bridges dynamic neural states to cognition and behaviors. Following this insight, our study aimed to (1) compare the efficacy of common burst detection algorithms under varying signal-to-noise ratios and event durations using synthetic signals and (2) establish a strategic guideline for selecting the optimal algorithm for real datasets with undefined properties.Approach.We tested the robustness of burst detection algorithms using a simulation dataset comprising bursts of multiple frequencies. To systematically assess their performance, we used a metric called 'detection confidence', quantifying classification accuracy and temporal precision in a balanced manner. Given that burst properties in empirical data are often unknown in advance, we then proposed a selection rule to identify an optimal algorithm for a given dataset and validated its application on local field potentials of basolateral amygdala recorded from male mice (n=8) exposed to a natural threat.Main Results.Our simulation-based evaluation demonstrated that burst detection is contingent upon event duration, whereas accurately pinpointing burst onsets is more susceptible to noise level. For real data, the algorithm chosen based on the selection rule exhibited superior detection and temporal accuracy, although its statistical significance differed across frequency bands. Notably, the algorithm chosen by human visual screening differed from the one recommended by the rule, implying a potential misalignment between human priors and mathematical assumptions of the algorithms.Significance.Therefore, our findings underscore that the precise detection of transient bursts is fundamentally influenced by the chosen algorithm. The proposed algorithm-selection rule suggests a potentially viable solution, while also emphasizing the inherent limitations originating from algorithmic design and volatile performances across datasets. Consequently, this study cautions against relying solely on heuristic-based approaches, advocating for a careful algorithm selection in burst detection studies.

Development and preliminary validation of a virtual reality memory test for assessing visuospatial memory.

Background: Visuospatial memory impairment is a common symptom of Alzheimer's disease; however, conventional visuospatial memory tests are insufficient to fully reflect visuospatial memory impairment in daily life. Methods: To address patients' difficulties in locating and recalling misplaced objects, we introduced a novel visuospatial memory test, the Hidden Objects Test (HOT), conducted in a virtual environment. We categorized HOT scores into prospective memory, item free-recall, place free-recall, item recognition, and place-item matching scores. To validate the VR memory test, we compared HOT scores among individuals with Alzheimer's disease (AD), amnestic mild cognitive impairment (aMCI), and normal controls (NC), and also compared these scores with those of conventional neuropsychological tests. We tracked the participants' movement paths in the virtual environment and assessed basic features, such as total distance, duration, and speed. Additionally, we performed walking trajectory pattern mining such as outlier and stay-point detection. Results: We designed and implemented the HOT to simulate a house's living room and assess participants' ability to locate hidden objects. Our preliminary results showed that the total HOT score differed among 17 patients with AD, 14 with aMCI, and 15 NC (p < 0.001). The total HOT score correlated positively with conventional memory test scores (p < 0.001). Walking trajectories showed that patients with AD and aMCI wandered rather than going straight to the hidden objects. In terms of basic features, the total duration was significantly greater in AD than in NC (p = 0.008). In terms of trajectory pattern mining, the number of outliers, which were over 95% of the estimated trajectory, was significantly higher in AD than in NC (p = 0.002). The number of stay points, an index in which participants stayed in the same position for more than 2 s, was significantly higher in patients with AD and aMCI compared with NC (AD vs. NC: p = 0.003, aMCI vs. NC: p = 0.019). Conclusion: The HOT simulating real life showed potential as an ecologically valid test for assessing visuospatial memory function in daily life. Walking trajectory analysis suggested that patients with AD and aMCI wandered rather than going straight toward the hidden objects.

The endocannabinoid N-arachidonoyl dopamine is critical for hyperalgesia induced by chronic sleep disruption.

Chronic pain is highly prevalent and is linked to a broad range of comorbidities, including sleep disorders. Epidemiological and clinical evidence suggests that chronic sleep disruption (CSD) leads to heightened pain sensitivity, referred to as CSD-induced hyperalgesia. However, the underlying mechanisms are unclear. The thalamic reticular nucleus (TRN) has unique integrative functions in sensory processing, attention/arousal and sleep spindle generation. We report that the TRN played an important role in CSD-induced hyperalgesia in mice, through its projections to the ventroposterior region of the thalamus. Metabolomics revealed that the level of N-arachidonoyl dopamine (NADA), an endocannabinoid, was decreased in the TRN after CSD. Using a recently developed CB1 receptor (cannabinoid receptor 1) activity sensor with spatiotemporal resolution, CB1 receptor activity in the TRN was found to be decreased after CSD. Moreover, CSD-induced hyperalgesia was attenuated by local NADA administration to the TRN. Taken together, these results suggest that TRN NADA signaling is critical for CSD-induced hyperalgesia.

Nine-day continuous recording of EEG and 2-hour of high-density EEG under chronic sleep restriction in mice.

This work provides an EEG dataset collected from nine mice during the sleep deprivation (SD) paradigm for the sleep science community. It includes 9-day of continuous recording of the frontal and parietal EEG, accelerometer, and 2-hour of high-density EEG (HD-EEG) under SD and SD-free conditions. Eighteen hours of SD were conducted on 5 consecutive days. The HD-EEG data were saved in the EEGLAB format and stored as the brain imaging data structure (BIDS). These datasets can be used to (i) compare mouse HD-EEG to human HD-EEG, (ii) track oscillatory activities of the sleep EEG (e.g., slow waves, spindles) across the cortical regions under different conditions of sleep pressure, and (iii) investigate the cortical traveling waves in the mouse brain. We also provided Python code for basic analyses of this dataset, including the detection of slow waves and sleep spindles. We hope that our dataset will reveal hidden activities during sleep and lead to a better understanding of the functions and mechanisms of sleep.

Increases of Phosphorylated Tau (Ser202/Thr205) in the Olfactory Regions Are Associated with Impaired EEG and Olfactory Behavior in Traumatic Brain Injury Mice.

Traumatic brain injury (TBI) leads to long-term cognitive impairments, with an increased risk for neurodegenerative and psychiatric disorders. Among these various impairments, olfactory dysfunction is one of the most common symptoms in TBI patients. However, there are very few studies that show the association between olfactory dysfunction and repetitive TBI. To investigate the effects of repetitive TBI on olfactory functioning and the related pathological neuronal injuries in mice, we applied a weight-drop model of TBI and performed neuropathological examinations and electroencephalography (EEG) in olfactory-bulb-associated areas. Through neuropathological examinations, we found significant increases of amyloid precursor protein (APP) and phosphorylated Tau (p-Tau) (S202/T205) in olfactory-bulb-associated areas. Neuronal atrophy in the lateral anterior olfactory nucleus (AOL), granule layer olfactory bulb (GrO), and dorsal tenia tecta (DTT) was also found to be correlated with p-Tau levels. However, there was no difference in the total Tau levels in the olfactory-bulb-associated areas of TBI mice. Electroencephalography (EEG) of repetitive TBI mouse models showed impaired spontaneous delta oscillation, as well as altered cross-frequency coupling between delta phase and amplitudes of the fast oscillations in the resting-state olfactory bulb. Furthermore, abnormal alterations in EEG band powers were observed during the olfactory oddball paradigm test. TBI also led to impairments of the olfactory-function-associated behaviors. This study provides evidence of behavioral, neuropathological, and physiological alterations in the mouse olfactory system caused by repetitive TBI. Together, p-Tau alterations and EEG impairments may serve as important biomarkers of olfactory-track-associated dysfunctions in repetitive TBI.

High resolution electroencephalography in freely moving mice.

Electroencephalography (EEG) is a standard tool for monitoring brain states in humans. Understanding the molecular and cellular mechanisms underlying diverse EEG rhythms can be facilitated by using mouse models under molecular, pharmacological, or electrophysiological manipulations. The small size of the mouse brain, however, poses a severe limitation in the spatial information of EEG. To overcome this limitation, we devised a polyimide based microelectrode array (PBM array) with nanofabrication technologies. The microelectrode contains 32 electrodes, weighs 150 mg, and yields noise-insensitive signals when applied on the mouse skull. The high-density microelectrode allowed both global and focused mapping of high resolution EEG (HR-EEG) in the mouse brain. Mapping and dynamical analysis tools also have been developed to visualize the dynamical changes of spatially resolved mouse EEG. We demonstrated the validity and utility of mouse EEG in localization of the seizure onset in absence seizure model and phase dynamics of abnormal theta rhythm in transgenic mice. Dynamic tracking of the EEG map in genetically modified mice under freely moving conditions should allow study of the molecular and cellular mechanisms underlying the generation and dynamics of diverse EEG rhythms.

Destruction of ERP responses to deviance in an auditory oddball paradigm in amyloid infusion mice with memory deficits.

The amyloid-ß (Aß) oligomer is considered one of the major pathogens responsible for neuronal and synaptic loss in Alzheimer's disease (AD) brains. Although the neurotoxic mechanisms of Aß have been widely investigated, experimental evidence for the direct linkage between neural signaling and cognitive impairments in association with peptide oligomers is lacking. Here, we conducted an auditory oddball paradigm utilizing an Aß-infused Alzheimer's disease mouse model and interpreted the results based on Y-maze behavioral tests. We acutely injected Aß oligomers into the intracerebroventricular brain region of normal mice to induce Aß-associated cognitive impairments. During the auditory oddball paradigm, electroencephalograms (EEG) were recorded from frontal and parietal cortex of Aß-infused and control mice. The event-related potentials (ERPs) elicited by auditory stimuli showed no significant difference in Aß-infused mice compared to control mice. On the other hand, the differential ERP signature elicited by oddball sound stimuli was destructed in the Aß-infused mice group. We noticed that ERP traces to standard and deviant tones were not significantly different in the Aß group, while the control group showed differences in the amplitude of ERP components. In particular, the difference in the first negative component (N1) between standard and deviant tone, which indexes the sensory memory system, was significantly reduced in the parietal cortex of Aß-infused mice. These findings demonstrate the direct influence of Aß oligomers on the functional integrity of cortical areas in vivo. Furthermore, the N1 amplitude difference may provide a potential marker of sensory memory deficits in a mouse model of AD and yield additional targets for drug assessment in AD.

High-density EEG of auditory steady-state responses during stimulation of basal forebrain parvalbumin neurons.

We present high-density EEG datasets of auditory steady-state responses (ASSRs) recorded from the cortex of freely moving mice with or without optogenetic stimulation of basal forebrain parvalbumin (BF-PV) neurons, known as a subcortical hub circuit for the global workspace. The dataset of ASSRs without BF-PV stimulation (dataset 1) contains raw 36-channel EEG epochs of ASSRs elicited by 10, 20, 30, 40, and 50 Hz click trains and time stamps of stimulations. The dataset of ASSRs with BF-PV stimulation (dataset 2) contains raw 36-channel EEG epochs of 40-Hz ASSRs during BF-PV stimulation with latencies of 0, 6.25, 12.5, and 18.75 ms and time stamps of stimulations. We provide the datasets and step-by-step tutorial analysis scripts written in Python, allowing for descriptions of the event-related potentials, spectrograms, and the topography of power. We complement this experimental dataset with simulation results using a time-dependent perturbation on coupled oscillators. This publicly available dataset will be beneficial to the experimental and computational neuroscientists.