The Thalamocortical Mechanism Underlying the Generation and Regulation of the Auditory Steady-State Responses in Awake Mice.

The auditory steady-state response (ASSR) is a cortical oscillation induced by trains of 40 Hz acoustic stimuli. While the ASSR has been widely used in clinic measurement, the underlying neural mechanism remains poorly understood. In this study, we investigated the contribution of different stages of auditory thalamocortical pathway-medial geniculate body (MGB), thalamic reticular nucleus (TRN), and auditory cortex (AC)-to the generation and regulation of 40 Hz ASSR in C57BL/6 mice of both sexes. We found that the neural response synchronizing to 40 Hz sound stimuli was most prominent in the GABAergic neurons in the granular layer of AC and the ventral division of MGB (MGBv), which were regulated by optogenetic manipulation of TRN neurons. Behavioral experiments confirmed that disrupting TRN activity has a detrimental effect on the ability of mice to discriminate 40 Hz sounds. These findings revealed a thalamocortical mechanism helpful to interpret the results of clinical ASSR examinations.Significance Statement Our study contributes to clarifying the thalamocortical mechanisms underlying the generation and regulation of the auditory steady-state response (ASSR), which is commonly used in both clinical and neuroscience research to assess the integrity of auditory function. Combining a series of electrophysiological and optogenetic experiments, we demonstrate that the generation of cortical ASSR is dependent on the lemniscal thalamocortical projections originating from the ventral division of medial geniculate body to the GABAergic interneurons in the granule layer of the auditory cortex. Furthermore, the thalamocortical process for ASSR is strictly regulated by the activity of thalamic reticular nucleus (TRN) neurons. Behavioral experiments confirmed that dysfunction of TRN would cause a disruption of mice's behavioral performance in the auditory discrimination task.

Cortical and thalamic modulation of auditory gating in the posterior parietal cortex of awake mice.

Auditory gating (AG) is an adaptive mechanism for filtering out redundant acoustic stimuli to protect the brain against information overload. AG deficits have been found in many mental illnesses, including schizophrenia (SZ). However, the neural correlates of AG remain poorly understood. Here, we found that the posterior parietal cortex (PPC) shows an intermediate level of AG in auditory thalamocortical circuits, with a laminar profile in which the strongest AG is in the granular layer. Furthermore, AG of the PPC was decreased and increased by optogenetic inactivation of the medial dorsal thalamic nucleus (MD) and auditory cortex (AC), respectively. Optogenetically activating the axons from the MD and AC drove neural activities in the PPC without an obvious AG. These results indicated that AG in the PPC is determined by the integrated signal streams from the MD and AC in a bottom-up manner. We also found that a mouse model of SZ (postnatal administration of noncompetitive N-methyl-d-aspartate receptor antagonist) presented an AG deficit in the PPC, which may be inherited from the dysfunction of MD. Together, our findings reveal a neural circuit underlying the generation of AG in the PPC and its involvement in the AG deficit of SZ.

Perfluorooctanesulfonic acid exposure altered hypothalamic metabolism and disturbed male fecundity.

Previous studies have examined the effects of perfluorooctanesulfonic acid (PFOS) on disruption of the blood-testis barrier and spermatogenesis. Sertoli and Leydig cells were perturbed, resulting in a decrease in testosterone levels and sperm counts. However, the effects of PFOS on male fecundity are not limited to the testes. In this study, we demonstrated that oral PFOS exposure (1 µg/g BW and 5 µg/g BW) decreased the function of the Luteinizing hormone (LH)/Luteinizing hormone receptor (LHr) and decreased epididymal sperm motility. Consistently, testicular transcriptome analysis revealed that PFOS altered the expression of a cluster of genes associated with sperm motility and steroidogenesis. In mice exposed to PFOS, c-Fos immunostaining showed activation of the lateral septal nucleus (LS), paraventricular thalamus (PVT), locus coeruleus (LC), which are known to be related to anxiety-like behaviors. Metabolomic analyses of the hypothalamus revealed that exposure to PFOS perturbed the translation of proteins, as well as the biosynthesis of neurotransmitters and neuromodulators. Altogether, the activation of brain nuclei, shift of hypothalamic metabolome, and reduction of LH/LHr circuit resulted from PFOS exposure suggested the toxicant's systematic effects on male reproduction.

Effect of locomotion on the auditory steady state response of head-fixed mice.

OBJECTIVES: Electroencephalographic (EEG) examinations of the auditory steady-state response (ASSR) can non-invasively probe cortical function to generate the gamma-band (40 Hz) oscillation, which is increasingly applied to the neurophysiological studies on the rodent models of psychiatric disorders. Though, it has been well established that the brain activities are significantly modulated by the behavioural state (such as locomotion), how the ASSR is affected remains unclear. METHODS: We investigated the effect of locomotion by recording local field potential (LFP) evoked by 40-Hz click-train from multiple brain areas: auditory cortex (AC), medial geniculate body (MGB), hippocampus (HP) and prefrontal cortex (PFC), in head-fixed mice free to run on a treadmill. Comparisons were conducted on the LFPs during spontaneous movement and stationary conditions. RESULTS: We found that in both the auditory (AC and MGB) and non-auditory areas (HP and PFC), locomotion reduced the initial negative deflection of LFP (early response during 0-100 ms from stimulus onset), and had no significant effect on the ASSR phase-locking to the late stimulus (100-500 ms). CONCLUSIONS: Our results suggest that different neural mechanisms contribute to the early response and ASSR, and the ASSR is a more robust biomarker to investigate the pathogenesis of neuropsychiatric disorders.

Electrical stimulation of the lateral cerebellar nucleus promotes neurogenesis in rats after motor cortical ischemia.

Deep brain stimulation (DBS) has been tentatively explored to promote motor recovery after stroke. Stroke could transiently activate endogenous self-repair processes, including neurogenesis in the subventricular zone (SVZ). In this regard, it is of considerable clinical interest to study whether DBS of the lateral cerebellar nucleus (LCN) could promote neurogenesis in the SVZ for functional recovery after stroke. In the present study, rats were trained on the pasta matrix reaching task and the ladder rung walking task before surgery. And then an electrode was implanted in the LCN following cortical ischemia induced by endothelin-1 injection. After 1 week of recovery, LCN DBS coupled with motor training for two weeks promoted motor function recovery, and reduced the infarct volumes post-ischemia. LCN DBS augmented poststroke neurogenetic responses, characterized by proliferation of neural progenitor cells (NPCs) and neuroblasts in the SVZ and subsequent differentiation into neurons in the ischemic penumbra at 21 days poststroke. DBS with the same stimulus parameters at 1 month after ischemia could also increase nascent neuroblasts in the SVZ and newly matured neurons in the perilesional cortex at 42 days poststroke. These results suggest that LCN DBS promotes endogenous neurogenesis for neurorestoration after cortical ischemia.

Aberrant Auditory Steady-State Response of Awake Mice After Single Application of the NMDA Receptor Antagonist MK-801 Into the Medial Geniculate Body.

BACKGROUND: Systemic administration of noncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonists such as MK-801 is widely used to model psychosis of schizophrenia (SZ). Acute systemic MK-801 in rodents caused an increase of the auditory steady-state responses (ASSRs), the oscillatory neural responses to periodic auditory stimulation, while most studies in patients with SZ reported a decrease of ASSRs. This inconsistency may be attributable to the comprehensive effects of systemic administration of MK-801. Here, we examined how the ASSR is affected by selectively blocking NMDAR in the thalamus. METHODS: We implanted multiple electrodes in the auditory cortex (AC) and prefrontal cortex to simultaneously record the local field potential and spike activity (SA) of multiple sites from awake mice. Click-trains at a 40-Hz repetition rate were used to evoke the ASSR. We compared the mean trial power and phase-locking factor and the firing rate of SA before and after microinjection of MK-801 (1.5 µg) into the medial geniculate body (MGB). RESULTS: We found that both the AC and prefrontal cortex showed a transient local field potential response at the onset of click-train stimulus, which was less affected by the application of MK-801 in the MGB. Following the onset response, the AC also showed a response continuing throughout the stimulus period, corresponding to the ASSR, which was suppressed by the application of MK-801. CONCLUSION: Our data suggest that the MGB is one of the generators of ASSR, and NMDAR hypofunction in the thalamocortical projection may account for the ASSR deficits in SZ.

Origin identification of Chinese Maca using electronic nose coupled with GC-MS.

Maca (Lepidium meyenii Walp.), originated in the high Andes of Peru, is rich in nutrients and phytochemicals. As a new resource food in China, Maca suffers marketing disorders due to the limitation of basic research. Due to the close relationship of Maca quality and origin of place, it's of scientific, economic and social importance to set up a rapid, reliable and efficient method to identify Maca origin. In the present study, 303 Maca samples were collected from 101 villages of the main producing area in China. Using electronic nose and BP neutral network algorithm, a Maca odor database was set up to trace the origin. GC-MS was then employed to analyze the characteristic components qualitatively and semi-quantitatively. As a result, very significant differences (p < 0.01) were detected in the volatile components of Maca from different areas. This study not only constructs a network model to forecast the Maca origin, but also reveals the relationship between Maca odor fingerprints and origins.

Emotional arousal modifies auditory steady state response in the auditory cortex and prefrontal cortex of rats.

Emotional state has been shown to influence cognitive performance. However, the influence of mood on auditory processing is not fully understood. The auditory steady state response (ASSR) is the entrainment of neural activities elicited by periodic auditory stimulation, which is commonly used to evaluate the sensory and cognitive functions of brain. It has been shown that ASSR at 40 Hz is impaired at some psychotic disorders, such as schizophrenia and bipolar disorder. The primary goal of this study is to investigate the effect of emotional arousal on ASSR. To this end, we performed simultaneous recordings of local field potential (LFP) in response to 40 Hz click-train stimuli in the primary auditory cortex (A1) and medial prefront cortex (mPFC) of rats. During the electrophysiological recording, a negative mood was induced by means of the foot shocks occurred randomly in the inter-stimulus intervals. We found that both the power and phase-locking of ASSR in A1 were significantly increased under arousal condition, and phase-locking of ASSR in mPFC was also increased. The enhanced ASSRs were accompanied by an increase in coherence between A1 and mPFC. Our results suggest that A1-to-mPFC information transfer is enhanced under arousal state and the functional connectivity between mPFC and A1 may contribute to the emotional modulation of auditory process.

Efficient U(VI) Reduction and Sequestration by Ti2CT x MXene.

Although reduction of highly mobile U(VI) to less soluble U(IV) has been long considered an effective approach to in situ environmental remediation of uranium, candidate reducing agents are largely limited to Fe-based materials and microbials. The importance of titanium-containing compounds in natural uranium ore deposits suggests a role for titanium in uranium migration. Herein, for the first time, a two-dimensional transition metal carbide, Ti2CT x, is shown to efficiently remove uranium via a sorption-reduction strategy. Batch experiments demonstrate that TiC2T x exhibits excellent U(VI) removal over a wide pH range, with an uptake capacity of 470 mg g-1 at pH 3.0. The mechanism for U(VI) to U(IV) reduction by Ti2CT x was deciphered by X-ray absorption spectroscopy and diffraction and photoelectron spectroscopy. The reduced U(IV) species at low pH is identified as mononuclear with bidendate binding to the MXene substrate. At near-neutral pH, nanoparticles of the UO2+ x phase adsorb to the substrate with some Ti2CT x transformed to amorphous TiO2. A subsequent in-depth study suggests Ti2CT x materials may be potential candidates for permeable reactive barriers in the treatment of wastewaters from uranium mining. This work highlights reduction-induced immobilization of U(VI) by Ti2CT x MXene including a pH-dependent reduction mechanism that might promote applications of titanium-based materials in the elimination of other oxidized contaminants.

Enhanced Photocatalytic Removal of Uranium(VI) from Aqueous Solution by Magnetic TiO2/Fe3O4 and Its Graphene Composite.

The separation and recovery of uranium from radioactive wastewater is important from the standpoints of environmental protection and uranium reuse. In the present work, magnetically collectable TiO2/Fe3O4 and its graphene composites were fabricated and utilized for the photocatalytical removal of U(VI) from aqueous solutions. It was found that, under ultraviolet (UV) irradiation, the photoreactivity of TiO2/Fe3O4 for the reduction of U(VI) was 19.3 times higher than that of pure TiO2, which is strongly correlated with the Fe0 and additional Fe(II) generated from the reduction of Fe3O4 by TiO2 photoelectrons. The effects of initial uranium concentration, solution pH, ionic strength, the composition of wastewater, and organic pollutants on the U(VI) removal by TiO2/Fe3O4 were systematically investigated. The results demonstrated its excellent performance in the cleanup of uranium contamination. As graphene can efficiently attract the TiO2 photoelectrons and thus decrease their transfer to Fe3O4, the photodissolution of Fe3O4 in the TiO2/graphene/Fe3O4 composite can be largely alleviated compared to that of the TiO2/Fe3O4, rendering this ternary composite a much higher stability. In addition, scanning electron microscopy (SEM), X-ray diffraction (XRD), X-ray absorption near edge spectroscopy (XANES), and X-ray photoelectron spectroscopy (XPS) were used to explore the reaction mechanisms.

Efficient removal of uranium from aqueous solution by zero-valent iron nanoparticle and its graphene composite.

Zero-valent iron nanoparticle (ZVI-np) and its graphene composites were prepared and applied in the removal of uranium under anoxic conditions. It was found that solutions containing 24 ppm U(VI) could be completely cleaned up by ZVI-nps, regardless of the presence of NaHCO3, humic acid, mimic groundwater constituents or the change of solution pH from 5 to 9, manifesting the promising potential of this reactive material in permeable reactive barrier (PRB) to remediate uranium-contaminated groundwater. In the measurement of maximum sorption capacity, removal efficiency of uranium kept at 100% until C0(U) = 643 ppm, and the saturation sorption of 8173 mg U/g ZVI-nps was achieved at C0(U) = 714 ppm. In addition, reaction mechanisms were clarified based on the results of SEM, XRD, XANES, and chemical leaching in (NH4)2CO3 solution. Partially reductive precipitation of U(VI) as U3O7 was prevalent when sufficient iron was available; nevertheless, hydrolysis precipitation of U(VI) on surface would be predominant as iron got insufficient, characterized by releases of Fe(2+) ions. The dissolution of Fe(0) cores was assigned to be the driving force of continuous formation of U(VI) (hydr)oxide. The incorporation of graphene supporting matrix was found to facilitate faster removal rate and higher U(VI) reduction ratio, thus benefitting the long-term immobilization of uranium in geochemical environment.