Subthreshold oscillations generated by TTX-sensitive sodium currents in dorsal cochlear nucleus pyramidal cells

During intracellular recordings in rodent brainstem slice preparations, dorsal cochlear nucleus (DCN) pyramidal cells (PCs) exhibit characteristic discharge patterns to depolarizing current injection that depend on the membrane potential from which the responses are evoked. When depolarized from hyperpolarized potentials, PCs can respond with a short-latency action potential followed by a long silent interval (pauser) or a train of action potentials with a long latency (buildup). During the silent intervals in a pauser or a buildup response, the membrane potential slowly depolarizes towards spike threshold, often exhibiting distinct voltage oscillations of 1–2 mV before the first spike. The subthreshold voltage oscillations were investigated using whole cell recordings from DCN PCs in rat pup (P10–14) brainstem slices. The oscillations were unaffected by excitatory and inhibitory neurotransmitter antagonists, and were not temporally locked to the onset of the depolarization. The oscillations typically became larger as spike threshold was approached, and had a characteristic frequency between 40 and 100 Hz. In the presence of tetrodotoxin (TTX, 500 nM), the oscillations were significantly suppressed, and could not be evoked at any voltage below or above spike threshold. The oscillations were not blocked by phenytoin or Cd²⁺, but they were affected by prior activity in the neuron for approximately 1 s. We conclude that voltage-gated Na⁺ channels are required to generate membrane oscillations during the buildup phase. We suggest that the subthreshold oscillations play a role in controlling spike timing in PCs when the membrane potential slowly approaches, or hovers near, spike threshold.     

阈下电刺激对心律及异位节律点影响的实验研究

采用持续（２～８ｓ）阈下电刺激的方法，对９只家兔进行了研究，以探讨其安全性和对室性异位节律点传播的抑制效果。结果提示：（１）用不同频率，以起搏阈值的７０％为阈下刺激持续刺激心房或心室，对心律无影响。未发现心房颤动、心室颤动等心律失常。Ｐ─Ｅ、ＱＲＳ、Ｑ─Ｔ间期无变化（Ｐ＞０．０５）．（２）这种阈下刺激可有效地阻滞模拟室性心动过速的传播（８／９），其作用有空间限制性。作者认为简化的阈下电刺激方法更便于临床应用。     

探讨基于近红外脑成像技术的阈下抑郁情志刺激反应机制研究可行性

近红外脑功能成像技术是近几年发展起来用于动态检测脑功能的方法,能够很好地反映抑郁人群认知活动期间大脑有氧代谢的变化,为阈下抑郁研究提供了一个新思路。本研究通过文献综述,结合中医情志理论,在过往研究的基础上基于近红外脑功能成像技术探讨中医情志刺激对阈下抑郁的反应机制,为后期研究提供理论与实践可行性的依据。     

Enhanced default mode network connectivity with ventral striatum in subthreshold depression individuals

Subthreshold depression (StD) is a highly prevalent condition associated with increased service utilization and social morbidity. Nevertheless, due to limitations in current diagnostic systems that set the boundary for major depressive disorder (MDD), very few brain imaging studies on the neurobiology of StD have been carried out, and its underlying neurobiological mechanism remains unclear. In recent years, accumulating evidence suggests that the disruption of the default mode network (DMN), a network involved in self-referential processing, affective cognition, and emotion regulation, is involved in major depressive disorder. Using independent component analysis, we investigated resting-state default mode network (DMN) functional connectivity (FC) changes in two cohorts of StD patients with different age ranges (young and middle-aged, n = 57) as well as matched controls (n = 79). We found significant FC increase between the DMN and ventral striatum (key region in the reward network), in both cohorts of StD patients in comparison with controls. In addition, we also found the FC between the DMN and ventral striatum was positively and significantly associated with scores on the Center for Epidemiologic Studies Depression Scale (CES-D), a measurement of depressive symptomatology. We speculate that this enhanced FC between the DMN and the ventral striatum may reflect a self-compensation to ameliorate the lowered reward function.     

Cyclothymic disorder: a critical review

Cyclothymic disorder is a subtype of bipolar disorder included in the Diagnostic and Statistical Manual of Mental Disorders since 1980, but largely neglected in research. Additionally, it is rarely diagnosed clinically, in spite of evidence that it may be the most prevalent form of bipolar disorder. Neglect has contributed to confusion about the diagnosis and clinical presentation of cyclothymic disorder. Its status as a mood disorder is also ambiguous due to overlap in terminology and symptoms with temperament and personality disorders. Subthreshold bipolar disorder appears more prevalent among young people than previously thought, and follows a range of trajectories from remission to escalation-raising questions about risk factors and traits associated with the varied course. Cyclothymic disorder may be an important diathesis for major mood disorders. Constructs such as cyclothymic disorder link major mood disorder and peri-clinical fluctuations of mood, thus warranting a prominent role in dimensional models of mood and psychopathology. Current evidence indicates that cyclothymic disorder is a prevalent and highly impairing disorder on the bipolar spectrum, with the potential to make unique contributions to our understanding of the risk factors and outcomes associated with bipolar disorder. The inclusion of cyclothymic disorder in future research studies is essential to accurate diagnosis and effective treatment for the full spectrum of bipolar disorder, as well as understanding the developmental trajectory of bipolar spectrum disorders.     

Additive subthreshold dose effects of cannabinoid CB(1) receptor antagonist and selective serotonin reuptake inhibitor in antidepressant behavioral tests

The main clinically used antidepressant drugs are selective monoamine reuptake inhibitors, including selective serotonin reuptake inhibitors (citalopram, sertraline), selective dopamine reuptake inhibitor (nomifensine) and selective noradrenaline reuptake inhibitor (reboxetine), but they have various side effects. Because cannabinoid CB(1) receptor antagonists (SR141716A, AM251) enhance monoamine release, they might be beneficial in the therapy of affective disorders. We hypothesized that the use of monoamine reuptake inhibitors in combination with cannabinoid CB(1) receptor antagonists would allow a lower dose of monoamine reuptake inhibitors to be used in the therapy of depression, thereby reducing or eliminating the side effects. To test this hypothesis, we examined the combination of SR141716A or AM251 with citalopram, sertraline, nomifensine or reboxetine at subthreshold doses to see whether these combinations would show an additive effect in the forced swimming test and the tail suspension test with mice. Subthreshold doses of cannabinoid CB(1) receptor antagonist and selective serotonin reuptake inhibitors, which separately had no effect on the immobility of mice in the tests, showed a clear effect when the drugs were administered at 40 and 30 min, respectively, before the tests, without any change of motor activity. Therefore, the use of subthreshold doses of these agents in combination might be useful to enhance mainly serotonergic neurotransmission, and to reduce or eliminate the side effects of citalopram and sertraline.     

Subthreshold conditions as precursors for full syndrome disorders: a 15-year longitudinal study of multiple diagnostic classes

Background:  There has been increasing interest in the distinction between subthreshold and full syndrome disorders and specifically whether subthreshold conditions escalate or predict the onset of full syndrome disorders over time. Most of these studies, however, examined whether a single subthreshold condition escalates into the full syndrome form of that disorder. Equally important, though, is whether subthreshold conditions are likely to develop other full syndrome disorders and whether these associations are maintained after adjusting for comorbidity.
Methods:  A 15-year longitudinal study of subthreshold psychiatric conditions was conducted with 1,505 community-drawn young adults. We examined whether 1) subthreshold major depression, bipolar, anxiety disorders, alcohol use, substance use, conduct disorder and/or ADHD were precursors for the corresponding (homotypic) full syndrome disorder; 2) subthreshold conditions were precursors for other (heterotypic) full syndrome disorders; and 3) these homotypic and heterotypic precursors persisted after adjusting for comorbidity.
Results:  Subthreshold major depression, anxiety, alcohol use, substance use, and conduct all escalated into their corresponding full syndrome and nearly all homotypic developments were maintained after adjusting for comorbid subthreshold and full syndrome conditions. Many heterotypic associations were also observed and most remained after controlling for comorbidity, particularly among externalizing disorders (e.g., alcohol, substance, conduct/antisocial personality disorder).
Conclusions:  Many subthreshold conditions have predictive validity as they may represent precursors for full syndrome disorders. Alternatively, dimensional conceptualizations of psychopathology which include these more minor conditions may yield greater validity. Subthreshold conditions may represent good targets for preventive interventions.     

电刺激致痫大鼠惊厥阈下脑放电动物模型的建立

目的　建立惊厥阈下脑放电动物模型，研究惊厥阈下脑放电（ＳＣＤ） 对大鼠空间变换学习记忆的影响。方法　选用雄性Ｗｉｓｔａｒ 大鼠１８ 只，采用慢性电极埋植法，在连续ＥＣｏＧ 记录下给予大鼠前额叶皮层电刺激，同时观察大鼠行为及脑电变化。结果　当３０ ～５０ μＡ 电刺激时可在额叶皮层引起４ ．５～５ Ｈｚ 单发或连续的高波幅棘慢波，海马则为与皮层同步的高波幅θ节律，无临床惊厥表现。结论　３０ ～５０ μＡ 电刺激可引起皮层和海马的惊厥阈下放电。