Impact of Second Messenger Modulation on Activity-Dependent and Basal Properties of Excitatory Synapses

Cognitive processing in the central nervous system relies on accurate information propagation; neurotransmission is the fundamental mechanism underlying network information flow. Because network information is coded by the timing and the strength of neuronal activity, synaptic properties that translate neuronal activity into synaptic output profoundly determine the precision of information transfer. Synaptic properties are in turn shaped by changes in network activity to ensure appropriate synaptic output. Activity-dependent adjustment of synaptic properties is often initiated by second messenger signals. Understanding how second messengers sculpt synaptic properties and produce changes in synaptic output is key for elucidating the interplay between network activity and synaptic properties. We studied the effect of second messenger modification on activity-dependent and static properties of rat hippocampal excitatory synapses using electrophysiological and optical approaches. We focused on two second-messenger pathways that potentiate transmission: cAMP and diacyl glycerol: DAG) signals. In parallel, we also compared the effects of manipulating calcium influx, which is known to potentiate synaptic transmission through increasing release probability: Pr). During high frequency stimulation, we found that both cAMP and DAG signals potentiated phasic transmission, as previously characterized. In parallel with increasing phasic transmission, the modulators also enhanced high-frequency associated asynchronous transmission, which emerges late during stimulus trains and is relatively long-lasting. However, such parallel potentiation of phasic and asynchronous transmission was not seen in elevated calcium; high calcium preferentially promoted asynchronous transmission. With low frequency stimulation, we found that cAMP and high calcium enhanced synaptic output by potentiating synapses with basally high Pr. Conversely, DAG signals recruited neurotransmission from both high Pr and low Pr terminals, which include presynaptically quiescent synapses. Taken together, these results suggest that second messenger modulation of synapses differentially shapes the static properties of the synapses; second messengers also fine-tune activity-dependent synaptic responses differently from manipulating calcium influx. These results likely have physiological relevance to second messenger-dependent sculpting of temporal and spatial synaptic properties

Cooling mechanical resonators to quantum ground state from room temperature

Ground-state cooling of mesoscopic mechanical resonators is a fundamental requirement for test of quantum theory and for implementation of quantum information. We analyze the cavity optomechanical cooling limits in the intermediate coupling regime, where the light-enhanced optomechanical coupling strength is comparable with the cavity decay rate. It is found that in this regime the cooling breaks through the limits in both the strong and weak coupling regimes. The lowest cooling limit is derived analytically at the optimal conditions of cavity decay rate and coupling strength. In essence, cooling to the quantum ground state requires $Q_{\mathrm{m}}>2.4n_{\mathrm{th}}$, with $Q_{\mathrm{m}}$ being the mechanical quality factor and $n_{\mathrm{th}}$ being the thermal phonon number. Remarkably, ground-state cooling is achievable starting from room temperature, when mechanical $Q$-frequency product $Q_{\mathrm{m}}{\nu>1.5}\times10^{13}$, and both of the cavity decay rate and the coupling strength exceed the thermal decoherence rate. Our study provides a general framework for optimizing the backaction cooling of mesoscopic mechanical resonators

Dynamic dissipative cooling of a mechanical oscillator in strong-coupling optomechanics

Cooling of mesoscopic mechanical resonators represents a primary concern in cavity optomechanics. Here in the strong optomechanical coupling regime, we propose to dynamically control the cavity dissipation, which is able to significantly accelerate the cooling process while strongly suppressing the heating noise. Furthermore, the dynamic control is capable of overcoming quantum backaction and reducing the cooling limit by several orders of magnitude. The dynamic dissipation control provides new insights for tailoring the optomechanical interaction and offers the prospect of exploring macroscopic quantum physics.Comment: accepetd in Physical Review Letter

Calcium-independent inhibitory G-protein signaling induces persistent presynaptic muting of hippocampal synapses

Adaptive forms of synaptic plasticity that reduce excitatory synaptic transmission in response to prolonged increases in neuronal activity may prevent runaway positive feedback in neuronal circuits. In hippocampal neurons, for example, glutamatergic presynaptic terminals are selectively silenced, creating mute synapses, after periods of increased neuronal activity or sustained depolarization. Previous work suggests that cAMP-dependent and proteasome-dependent mechanisms participate in silencing induction by depolarization, but upstream activators are unknown. We, therefore, tested the role of calcium and G-protein signaling in silencing induction in cultured hippocampal neurons. We found that silencing induction by depolarization was not dependent on rises in intracellular calcium, from either extracellular or intracellular sources. Silencing was, however, pertussis toxin sensitive, which suggests that inhibitory G-proteins are recruited. Surprisingly, blocking four common inhibitory G-protein-coupled receptors (GPCRs) (adenosine A(1) receptors, GABA(B) receptors, metabotropic glutamate receptors, and CB(1) cannabinoid receptors) and one ionotropic receptor with metabotropic properties (kainate receptors) failed to prevent depolarization-induced silencing. Activating a subset of these GPCRs (A(1) and GABA(B)) with agonist application induced silencing, however, which supports the hypothesis that G-protein activation is a critical step in silencing. Overall, our results suggest that depolarization activates silencing through an atypical GPCR or through receptor-independent G-protein activation. GPCR agonist-induced silencing exhibited dependence on the ubiquitin-proteasome system, as was shown previously for depolarization-induced silencing, implicating the degradation of vital synaptic proteins in silencing by GPCR activation. These data suggest that presynaptic muting in hippocampal neurons uses a G-protein-dependent but calcium-independent mechanism to depress presynaptic vesicle release

Effects of Personal Characteristics on Learner Online Learning Readiness

Nowadays many educational institutions have embraced online education to cater for flexible and student-centered learning. Through online education, students have an opportunity to gain an education at their own convenience, in terms of time and place. However, it is argued that students are less satisfied with online learning than with traditional classroom learning. As online education continues to expand, the need for determining and maintaining quality online education is becoming an important issue. Therefore, it is important to discern which qualities are necessary for students‘ achievement and satisfaction in an online learning environment (OLE). While numerous studies on the qualities of online learners have been conducted, the factors that contribute to success in OLEs have not been adequately described. Therefore, it is important to examine learner characteristics to see their effects on student success in an online environment, which in turn facilitates high quality of online learning. This paper reports on what and how personal characteristics significantly affect students‘ online learning readiness at Curtin University of Technology, Sarawak Malaysia. Natural sampling was used to identify the sample and the study sample consisted of 350 voluntary participants. Quantitative method was used to collect relevant data in this study. A questionnaire was developed to gather data on learner personal characteristics, and a diagnostic tool, Tertiary Students‘ Readiness for Online Learning (TSROL), developed by Hitendra Pillay, Kym Irving and Megan Tones was adopted to assess learner online learning readiness. The TSROL has 20 items grouped into four factors: Technical skills (TS), Computer self-efficacy (CS-E), Learning preferences (LP) and Attitudes towards computers (AC). Moreover, confirmatory data analysis was adopted in this study. A one- way analysis of variance (ANOVA) was used to determine if there were significant differences in online learning readiness across the personal characteristics. The statistical results validate that some personal characteristics significantly affect learners‘ online learning readiness