关于B族Ⅰ型清道夫受体研究进展的认识

B族I型清道夫受体(SR-BI)具有经典的清道夫受体功能,且是HDL的高亲和力受体,并能介导HDL中胆固醇的选择性摄取、影响血浆HDL-C水平以及介导非酯化胆固醇在脂蛋白和细胞之间的双向运动,具有抗动脉粥样硬化的作用。其研究过程反映了相对真理与绝对真理、现象与本质的辩证关系。当新现象被逐一发现,相对真理就逐渐确立,而循序渐进并运用创造性思维,最终将揭示事物的本质,实现相对真理向绝对真理的转化。     

Postnatal maternal symptoms of depression and child emotion dysregulation: The mediation role of infant EEG alpha asymmetry

In a community-based sample of 104 infants and their mothers, we hypothesized a pathway from postnatal maternal symptoms of depression to child emotion dysregulation, and tested at 6 months of age the mediation role of alpha asymmetry at frontal and parietal sites. We recorded infant resting-state EEG at 6 months of age. Child emotion dysregulation was measured at 24 months by the Child Behavior Checklist Dysregulation Profile derived from the CBCL 1½-5. Maternal depression symptoms were scored 6 months after the delivery by the Anxious/Depressed scale of the Adult Self-Report. We used structural equation modeling to test the mediation model from maternal depression symptoms to child emotion dysregulation mediated by frontal and parietal alpha asymmetry. The mediation model provided an excellent fit to the data [χ2(3) = 3.088, p = .378; RMSEA = .017, CFI = .1.00; SRMR = 0.040] and explained 23.3% of the variance in child emotion dysregulation. The indirect path via parietal alpha asymmetry was significant (β = .065; SE = .033; 95% CI = .001–.139; p = .048), i.e. greater levels of maternal depression symptoms predicted left parietal alpha asymmetry, which predicted higher levels of child emotion dysregulation. The direct effect, i.e. the pathway linking maternal depression symptoms and child emotion dysregulation above and beyond the indirect effects, was also significant. We found evidence for a partial mediation role of left parietal alpha asymmetry in a longitudinal pathway from postnatal maternal symptoms of depression to child emotion dysregulation, providing support for left parietal asymmetry as an index of biological vulnerability to emotion dysregulation in the first years of life.     

Inhibition of mGluR1 and IP3Rs impairs long-term memory formation in young chicks

Calcium (Ca²⁺) is involved in a myriad of cellular functions in the brain including synaptic plasticity. However, the role of intracellular Ca²⁺ stores in memory processing remains poorly defined. The current study explored a role for glutamate-dependent intracellular Ca²⁺ release in memory processing via blockade of metabotropic glutamate receptor subtype 1 (mGluR1) and inositol (1,4,5)-trisphosphate receptors (IP₃Rs). Using a single-trial discrimination avoidance task developed for the young chick, administration of the specific and potent mGluR1 antagonist JNJ16259685 (500 nM, immediately post-training, ic), or the IP₃R antagonist Xestospongin C (5 μM, immediately post-training, ic), impaired retention from 90 min post-training. These findings are consistent with mGluR1 activating IP₃Rs to release intracellular Ca²⁺ required for long-term memory formation and have been interpreted within an LTP2 model. The consequences of different patterns of retention loss following ryanodine receptor (RyR) and IP₃R inhibition are discussed.     

Co-induction of long-term potentiation and long-term depression at a central synapse in the leech

Most studies of long-term potentiation (LTP) have focused on potentiation induced by the activation of postsynaptic NMDA receptors (NMDARs). However, it is now apparent that NMDAR-dependent signaling processes are not the only form of LTP operating in the brain [Malenka, R. C., & Bear, M. F. (2004). LTP and LTD: An embarrassment of riches. Neuron, 44, 5–21]. Previously, we have observed that LTP in leech central synapses made by the touch mechanosensory neurons onto the S interneuron was NMDAR-independent [Burrell, B. D., & Sahley, C. L. (2004). Multiple forms of long-term potentiation and long-term depression converge on a single interneuron in the leech CNS. Journal of Neuroscience, 24, 4011–4019]. Here we examine the cellular mechanisms mediating T-to-S (T → S) LTP and find that its induction requires activation of metabotropic glutamate receptors (mGluRs), voltage-dependent Ca²⁺ channels (VDCCs) and protein kinase C (PKC). Surprisingly, whenever LTP was pharmacologically inhibited, long-term depression (LTD) was observed at the tetanized synapse, indicating that LTP and LTD were activated at the same time in the same synaptic pathway. This co-induction of LTP and LTD likely plays an important role in activity-dependent regulation of synaptic transmission.     

Higher levels of estradiol replacement correlate with better spatial memory in surgically menopausal young and middle-aged rats

The current study investigated whether, for spatial reference memory, age impacts (1) sensitivity to surgical ovarian hormone loss (Ovx), (2) response to estradiol therapy (ET), and (3) the relation between circulating estradiol levels and memory scores in ovary-intact sham and Ovx plus ET rats. Young, middle-aged and aged Fischer-344 rats received sham, Ovx or Ovx plus ET treatments, and were then tested on the Morris maze. After the last test trial, a probe trial was given whereby the platform was removed. Circulating estradiol levels were then determined and correlated with performance. In Study 1, Ovx facilitated learning on day one, but impaired performance after day one, in young rats. Ovx did not influence performance in middle-aged rats. In young and middle-aged Ovx rats, ET enhanced performance with higher exogenous estradiol levels correlating with better performance during testing and the probe trial. There was no relationship between endogenous estradiol levels and performance in sham young or middle-aged rats. Study 2 showed that, like middle-aged rats, aged rats were not impacted by Ovx. Further, for aged Ovx rats, the ET regimen that was beneficial at earlier ages was no longer effective during test trials, and had only minor benefits for platform localization as assessed by the probe trial. Collectively, the findings suggest that the effects of Ovx as well as responsivity to the currently utilized ET regimen changes with age. Further, there appears to be a distinction between sensitivity to Ovx and responsiveness to ET after Ovx for spatial reference memory performance.     

Habituation in Aplysia: The Cheshire Cat of neurobiology

The marine snail, Aplysia californica, is a valuable model system for cell biological studies of learning and memory. Aplysia exhibits a reflexive withdrawal of its gill and siphon in response to weak or moderate tactile stimulation of its skin. Repeated tactile stimulation causes this defensive withdrawal reflex to habituate. Both short-term habituation, lasting <30 min, and long-term habituation, which can last >24 h, have been reported in Aplysia. Habituation of the withdrawal reflex correlates with, and is in part due to, depression of transmission at the monosynaptic connection between mechanoreceptive sensory neurons and motor neurons within the abdominal ganglion. Habituation-related short-term depression of the sensorimotor synapse appears to be due exclusively to presynaptic changes. However, changes within the sensory neuron, by themselves, do not account for more persistent depression of the sensorimotor synapse. Recent behavioral work suggests that long-term habituation in Aplysia critically involves postsynaptic processes, specifically, activation of AMPA- and NMDA-type receptors. In addition, long-term habituation requires activity of protein phosphatases, including protein phosphatases 1, 2A, and 2B, as well as activity of voltage-dependent Ca²⁺ channels. Cellular work has succeeded in demonstrating long-term, homosynaptic depression (LTD) of the sensorimotor synapse in dissociated cell culture and, more recently, LTD of the glutamate response of isolated motor neurons in culture (“hemisynaptic” LTD). These in vitro forms of LTD have mechanistic parallels to long-term habituation. In particular, homosynaptic LTD of the sensorimotor synapse requires elevated intracellular Ca²⁺ within the motor neuron, and hemisynaptic LTD requires activity of AMPA- and NMDA-type receptors. In addition, activation of group I and II metabotropic glutamate receptors (mGluRs) can induce hemisynaptic LTD. The demonstration of LTD in vitro opens up a promising new avenue for attempts to relate long-term habituation to cellular changes within the nervous system of Aplysia.     

Fatty acid amide hydrolase (FAAH) knockout mice exhibit enhanced acquisition of an aversive, but not of an appetitive, Barnes maze task

It is well established that genetic deletion or pharmacological inhibition of the CB₁ receptor disrupts extinction learning in aversive conditioning tasks, but not in appetitive tasks. Consistent with these findings is that genetic deletion or pharmacological inhibition of fatty acid amide hydrolase (FAAH), the primary catabolic enzyme of the endogenous cannabinoid anandamide (AEA), accelerates acquisition as well as extinction in aversive conditioning tasks. However, it is unknown whether FAAH blockade will affect acquisition in an appetitive conditioning task. Therefore, in the present study, we assessed FAAH (−/−) and (+/+) mice in appetitive and aversive Barnes maze conditioning procedures. Here we report that FAAH (−/−) mice displayed accelerated acquisition rates in an aversively-motivated, but not in the appetitively-motivated, Barnes maze task. The CB₁ receptor antagonist, rimonabant attenuated enhanced acquisition in the aversive procedure, consistent with the idea that elevated AEA levels mediate this apparent nootropic effect. These findings support the hypothesis that stimulation of the endocannabinoid system enhances learned behavior in aversive, but not appetitive, conditioning paradigms.     

前额皮层肾上腺素能受体在工作记忆中的作用

前额皮层去甲肾上腺素能神经支配主要来自脑干蓝斑核。前额皮层存在不同类型的肾上腺素能受体。其中突触后α2及β2肾上腺素能受体的激活提高工作记忆;α1及β1肾上腺素能受体的激活损害工作记忆。不同受体是通过激活不同的信号通路发挥对工作记忆的调节作用。来自人类被试的研究结果与对动物的研究结果之间尚存在不一致。了解前额皮层不同肾上腺素受体的作用为开发治疗与前额皮层功能失调相关疾病的药物提供了新的方向。     

Reliability Beyond Theory and Into Practice

The critical reactions of Bentler (2009, doi:), Green and Yang (2009a, doi:; 2009b, doi:), and Revelle and Zinbarg (2009, doi:) to Sijtsma’s (2009, doi:) paper on Cronbach’s alpha are addressed. The dissemination of psychometric knowledge among substantive researchers is discussed.     

Hemispheric Asymmetry and Regional Differences in Electroencephalographic Alpha Activity at the Wake-Sleep Transition

Electroencephalographic (EEG) alpha activity at the wake-sleep transition was studied in six right-handed adults in terms of hemispheric asymmetry and regional differences. Twelve-channel EEGs with linked mastoid references were recorded together with horizontal and vertical electro-oculograms (EOGs). Two types of alpha coefficient were obtained every 5.12 s by computing the relative proportion of right vs. left alpha band power and of anterior vs. posterior alpha band power. Four stages were scored using EEG sleep patterns (theta waves, vertex sharp waves, spindles, and K complex) and slow eye movement (SEM): stage W had neither EEG sleep patterns nor SEM; stage D1 had SEM and no EEG sleep patterns; stage D2 had theta waves or vertex sharp waves and SEM; stage S had spindles or K complex without SEM. It was found that the two types of alpha coefficient changed as a function of EEG-EOG stage and were correlated. Right-decreased and anterior-shifted alpha activities were manifest at stages D2 and S. Drowsiness was considered to be a heterogeneous state, exhibiting different spatial changes in alpha activity between stages D1 and D2.