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.

Effects of Organic Chromium Yeast on Performance, Meat Quality, and Serum Parameters of Grow-Finish Pigs.

Trivalent chromium (Cr) is an essential trace element for humans and animals. This study was conducted to investigate the effects of chromium(III) yeast (CrYst) on growth performance, carcass characteristics, meat traits, antioxidant status, immune traits, and serum biochemical parameters of grow-finish pigs. A total of 72 commercial hybrid barrows (Duroc × Landrace × Large White) of approximately 50 kg body weight were allocated into two dietary treatments randomly, which received a corn-soybean meal basal diet or a basal diet supplemented with 100 mg CrYst/kg. The trial duration was 11 weeks divided into three periods from body weights of 50-75 kg, 75-100 kg, and 100-110 kg, respectively. The results revealed that supplemental CrYst did not affect growth performance. Organic CrYst supplementation significantly decreased the backfat depth and increased the meat tenderness score and juiciness score values in pigs (P < 0.05), while other carcass traits and meat traits indexes were unaffected. CrYst addition significantly decreased serum malondialdehyde (MDA) content of pigs in the whole growth phase; significantly increased the serum levels of immunoglobulin G (IgG), total antioxidant capacity (T-AOC), glutathione peroxidase (GSH-Px), and reduced glutathione (GSH) in growing pigs; and also increased the serum IgG, IgM, and GSH concentrations in pigs during the finishing phase (P < 0.05). Additionally, diets supplemented with CrYst significantly decreased the serum high-density lipoprotein cholesterol (HDL-C) content in growing pigs and significantly increased the serum LDL-C level at the fattening period (P < 0.05), whereas no significant differences were observed for the other serum biochemical indexes compared to the control pigs. In conclusion, CrYst supplementation could reduce lipid peroxidation and backfat thickness and improve the meat tenderness and juiciness, immune traits, and antioxidant status of pigs.

An Orally Active Allosteric GLP-1 Receptor Agonist Is Neuroprotective in Cellular and Rodent Models of Stroke.

Diabetes is a major risk factor for the development of stroke. Glucagon-like peptide-1 receptor (GLP-1R) agonists have been in clinical use for the treatment of diabetes and also been reported to be neuroprotective in ischemic stroke. The quinoxaline 6,7-dichloro-2-methylsulfonyl-3-N-tert- butylaminoquinoxaline (DMB) is an agonist and allosteric modulator of the GLP-1R with the potential to increase the affinity of GLP-1 for its receptor. The aim of this study was to evaluate the neuroprotective effects of DMB on transient focal cerebral ischemia. In cultured cortical neurons, DMB activated the GLP-1R, leading to increased intracellular cAMP levels with an EC50 value about 100 fold that of exendin-4. Pretreatment of neurons with DMB protected against necrotic and apoptotic cell death was induced by oxygen-glucose deprivation (OGD). The neuroprotective effects of DMB were blocked by GLP-1R knockdown with shRNA but not by GLP-1R antagonism. In C57BL/6 mice, DMB was orally administered 30 min prior to middle cerebral artery occlusion (MCAO) surgery. DMB markedly reduced the cerebral infarct size and neurological deficits caused by MCAO and reperfusion. The neuroprotective effects were mediated by activation of the GLP-1R through the cAMP-PKA-CREB signaling pathway. DMB exhibited anti-apoptotic effects by modulating Bcl-2 family members. These results provide evidence that DMB, a small molecular GLP-1R agonist, attenuates transient focal cerebral ischemia injury and inhibits neuronal apoptosis induced by MCAO. Taken together, these data suggest that DMB is a potential neuroprotective agent against cerebral ischemia.