Effect of interstimulus interval on cortical proprioceptive responses to passive finger movements

Shortening of the interstimulus interval (ISI) generally leads to attenuation of cortical sensory responses. For proprioception, however, this ISI effect is still poorly known. Our aim was to characterize the ISI dependence of movement‐evoked proprioceptive cortical responses and to find the optimum ISI for proprioceptive stimulation. We measured, from 15 healthy adults, magnetoencephalographic responses to passive flexion and extension movements of the right index finger. The movements were generated by a movement actuator at fixed ISIs of 0.5, 1, 2, 4, 8, and 16 s, in separate blocks. The responses peaked at ~ 70 ms (extension) and ~ 90 ms (flexion) in the contralateral primary somatosensory cortex. The strength of the cortical source increased with the ISI, plateauing at the 8‐s ISI. Modeling the ISI dependence with an exponential saturation function revealed response lifetimes of 1.3 s (extension) and 2.2 s (flexion), implying that the maximum signal‐to‐noise ratio (SNR) in a given measurement time is achieved with ISIs of 1.7 s and 2.8 s respectively. We conclude that ISIs of 1.5–3 s should be used to maximize SNR in recordings of proprioceptive cortical responses to passive finger movements. Our findings can benefit the assessment of proprioceptive afference in both clinical and research settings.     

Glyburide treatment in gestational diabetes is associated with increased placental glucose transporter 1 expression and higher birth weight

Use of glyburide in gestational diabetes (GDM) has raised concerns about fetal and neonatal side effects, including increased birth weight. Placental nutrient transport is a key determinant of fetal growth, however the effect of glyburide on placental nutrient transporters is largely unknown. We hypothesized that glyburide treatment in GDM pregnancies is associated with increased expression of nutrient transporters in the syncytiotrophoblast plasma membranes.We collected placentas from GDM pregnancies who delivered at term and were treated with either diet modification (n = 15) or glyburide (n = 8). Syncytiotrophoblast microvillous (MVM) and basal (BM) plasma membranes were isolated and expression of glucose (glucose transporter 1; GLUT1), amino acid (sodium-coupled neutral amino acid transporter 2; SNAT2 and L-type amino acid transporter 1; LAT1) and fatty acid (fatty acid translocase; FAT/CD36, fatty acid transporter 2 and 4; FATP2, FATP4) transporters was determined by Western blot. Additionally, we determined GLUT1 expression by confocal microscopy in cultured primary human trophoblasts (PHT) after exposure to glyburide.Birth weight was higher in the glyburide-treated group as compared to diet-treated GDM women (3764 ± 126 g vs. 3386 ± 75 g; p < 0.05). GLUT1 expression was increased in both MVM (+50%; p < 0.01) and BM (+75%; p < 0.01). In contrast, MVM FAT/CD36 (−65%; p = 0.01) and FATP2 (−65%; p = 0.02) protein expression was reduced in mothers treated with glyburide. Glyburide increased membrane expression of GLUT1 in a dose-dependent manner in cultured PHT.This data is the first to show that glyburide increases GLUT1 expression in syncytiotrophoblast MVM and BM in GDM pregnancies, and may promote transplacental glucose delivery contributing to fetal overgrowth.     

Precise spike timing dynamics of hippocampal place cell activity sensitive to cholinergic disruption

New memory formation depends on both the hippocampus and modulatory effects of acetylcholine. The mechanism by which acetylcholine levels in the hippocampus enable new encoding remains poorly understood. Here, we tested the hypothesis that cholinergic modulation supports memory formation by leading to structured spike timing in the hippocampus. Specifically, we tested if phase precession in dorsal CA1 was reduced under the influence of a systemic cholinergic antagonist. Unit and field potential were recorded from the dorsal CA1 of rats as they completed laps on a circular track for food rewards before and during the influence of the systemically administered acetylcholine muscarinic receptor antagonist scopolamine. We found that scopolamine significantly reduced phase precession of spiking relative to the field theta, and that this was due to a decrease in the frequency of the spiking rhythmicity. We also found that the correlation between position and theta phase was significantly reduced. This effect was not due to changes in spatial tuning as tuning remained stable for those cells analyzed. Similarly, it was not due to changes in lap‐to‐lap reliability of spiking onset or offset relative to either position or phase as the reliability did not decrease following scopolamine administration. These findings support the hypothesis that memory impairments that follow muscarinic blockade are the result of degraded spike timing in the hippocampus.