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"Jones, R S"
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A critical role for NMDA receptors in parvalbumin interneurons for gamma rhythm induction and behavior
Synchronous recruitment of fast-spiking (FS) parvalbumin (PV) interneurons generates gamma oscillations, rhythms that emerge during performance of cognitive tasks. Administration of
N
-methyl-
D
-aspartate (NMDA) receptor antagonists alters gamma rhythms, and can induce cognitive as well as psychosis-like symptoms in humans. The disruption of NMDA receptor (NMDAR) signaling specifically in FS PV interneurons is therefore hypothesized to give rise to neural network dysfunction that could underlie these symptoms. To address the connection between NMDAR activity, FS PV interneurons, gamma oscillations and behavior, we generated mice lacking NMDAR neurotransmission only in PV cells (PV-Cre/NR1f/f mice). Here, we show that mutant mice exhibit enhanced baseline cortical gamma rhythms, impaired gamma rhythm induction after optogenetic drive of PV interneurons and reduced sensitivity to the effects of NMDAR antagonists on gamma oscillations and stereotypies. Mutant mice show largely normal behaviors except for selective cognitive impairments, including deficits in habituation, working memory and associative learning. Our results provide evidence for the critical role of NMDAR in PV interneurons for expression of normal gamma rhythms and specific cognitive behaviors.
Journal Article
Angular Velocities and Linear Accelerations Derived from Inertial Measurement Units Can Be Used as Proxy Measures of Knee Variables Associated with ACL Injury
Given the high rates of both primary and secondary anterior cruciate ligament (ACL) injuries in multidirectional field sports, there is a need to develop easily accessible methods for practitioners to monitor ACL injury risk. Field-based methods to assess knee variables associated with ACL injury are of particular interest to practitioners for monitoring injury risk in applied sports settings. Knee variables or proxy measures derived from wearable inertial measurement units (IMUs) may thus provide a powerful tool for efficient injury risk management. Therefore, the aim of this study was to identify whether there were correlations between laboratory-derived knee variables (knee range of motion (RoM), change in knee moment, and knee stiffness) and metrics derived from IMUs (angular velocities and accelerations) placed on the tibia and thigh, across a range of movements performed in practitioner assessments used to monitor ACL injury risk. Ground reaction forces, three-dimensional kinematics, and triaxial IMU data were recorded from nineteen healthy male participants performing bilateral and unilateral drop jumps, and a 90° cutting task. Spearman’s correlations were used to examine the correlations between knee variables and IMU-derived metrics. A significant strong positive correlation was observed between knee RoM and the area under the tibia angular velocity curve in all movements. Significant strong correlations were also observed in the unilateral drop jump between knee RoM, change in knee moment, and knee stiffness, and the area under the tibia acceleration curve (rs = 0.776, rs = −0.712, and rs = −0.765, respectively). A significant moderate correlation was observed between both knee RoM and knee stiffness, and the area under the thigh angular velocity curve (rs = 0.682 and rs = −0.641, respectively). The findings from this study suggest that it may be feasible to use IMU-derived angular velocities and acceleration measurements as proxy measures of knee variables in movements included in practitioner assessments used to monitor ACL injury risk.
Journal Article
Rapid Holocene thinning of an East Antarctic outlet glacier driven by marine ice sheet instability
Outlet glaciers grounded on a bed that deepens inland and extends below sea level are potentially vulnerable to ‘marine ice sheet instability’. This instability, which may lead to runaway ice loss, has been simulated in models, but its consequences have not been directly observed in geological records. Here we provide new surface-exposure ages from an outlet of the East Antarctic Ice Sheet that reveal rapid glacier thinning occurred approximately 7,000 years ago, in the absence of large environmental changes. Glacier thinning persisted for more than two and a half centuries, resulting in hundreds of metres of ice loss. Numerical simulations indicate that ice surface drawdown accelerated when the otherwise steadily retreating glacier encountered a bedrock trough. Together, the geological reconstruction and numerical simulations suggest that centennial-scale glacier thinning arose from unstable grounding line retreat. Capturing these instability processes in ice sheet models is important for predicting Antarctica’s future contribution to sea level change.
Irreversible ice loss from East Antarctic outlet glaciers during periods of ice sheet instability is yet to be observed in the geological record. Here, Jones
et al
. combine surface-exposure ages and model simulations to show the centennial-scale glacier thinning of Mackay Glacier during the mid-Holocene.
Journal Article
Patterns of ethanol intake in male rats with partial dopamine transporter deficiency
Mesolimbic dopamine signaling plays a major role in alcohol and substance use disorders as well as comorbidities such as anxiety and depression. Growing evidence suggests that alcohol drinking is modulated by the function of the dopamine transporter (DAT), which tightly regulates extracellular dopamine concentrations. Adult male rats on a Wistar Han background (DAT+/+) and rats with a partial DAT deletion (DAT+/−) were used in this study. First, using fast‐scan cyclic voltammetry in brain slices containing the nucleus accumbens core from ethanol‐naïve subjects, we measured greater evoked dopamine concentrations and slower dopamine reuptake in DAT+/− rats, consistent with increased dopamine signaling. Next, we measured ethanol drinking using the intermittent access two‐bottle choice paradigm (20% v/v ethanol vs. water) across 5 weeks. DAT+/− rats voluntarily consumed less ethanol during its initial availability (the first 30 min), especially after longer periods of deprivation. In addition, DAT+/− males consumed less ethanol that was adulterated with the bitter tastant quinine. These findings suggest that partial DAT blockade and concomitant increase in brain dopamine levels has potential to reduce drinking and ameliorate alcohol use disorder (AUD). We investigated patterns of ethanol drinking in male rats with partial deletion of dopamine transporters. Compared to wild‐types, DAT+/− animals do not as readily develop alcohol use disorder (AUD)‐like phenotypes.
Journal Article
Remineralization of Enamel Caries Can Decrease Optical Reflectivity
The remineralization of enamel caries can lead to distinct optical changes within a lesion. We hypothesized that the restoration of mineral volume would result in a measurable decrease in the depth-resolved reflectivity of polarized light from the lesion. To test this hypothesis, we measured optical changes in artificial caries undergoing remineralization as a function of depth, using Polarization-sensitive Optical Coherence Tomography (PS-OCT). Lesions were imaged non-destructively before and after exposure to a remineralization regimen. After imaging, microradiographs of histological thin sections indicated that the significant reflectivity reduction measured by PS-OCT accurately represented the increase in mineral content within a larger repaired surface zone. Mineral volume changes arising from remineralization can be measured on the basis of the optical reflectivity of the lesion.
Journal Article
The phenomenology of inner speech: comparison of schizophrenia patients with auditory verbal hallucinations and healthy controls
Despite the popularity of inner-speech theories of auditory verbal hallucinations (AVHs), little is known about the phenomenological qualities of inner speech in patients with schizophrenia who experience AVHs (Sz-AVHs), or how this compares to inner speech in the non-voice-hearing general population.
We asked Sz-AVHs (n=29) and a non-voice-hearing general population sample (n=42) a series of questions about their experiences of hearing voices, if present, and their inner speech.
The inner speech reported by patients and controls was found to be almost identical in all respects. Furthermore, phenomenological qualities of AVHs (e.g. second- or third-person voices) did not relate to corresponding qualities in inner speech.
No discernable differences were found between the inner speech reported by Sz-AVHs and healthy controls. Implications for inner-speech theories of AVHs are discussed.
Journal Article