Norms of vagal nerve activity,indexed by Heart Rate Variability,in cancer patients

Recent research has begun to show the role of the activity of the vagus nerve in cancer prognosis. However, it remains unknown whether cancer severity can impair vagal nerve activity. This study combined data (N = 657) of five different cancers (colorectal, pancreas, prostate, lung and ovarian) concerning patients’ Heart Rate Variability (HRV), a vagal nerve activity index. These data were compared to HRV levels of a healthy sample in another study. In addition, we examined the moderating effects of age, gender and cancer stage on HRV. The mean HRV of the cancer patients sample was significantly lower (HRV = 22 ms) compared to the healthy sample (HRV = 50 ms) (p < 0.000001). While age and gender did not significantly affect HRV, cancer patients with advanced stages had significantly lower HRV than those with early stages (p = 0.011). A possible bi-directional relation between cancer and vagal nerve activity is discussed. These findings are of importance for prognostication since they provide researchers and clinicians with expected values of vagal nerve activity in cancer patients.     

神经调节素对大鼠脑缺血再灌注损伤后炎症反应的抑制作用和机制研究

目的：研究神经调节素及基质金属蛋白酶-9对于小鼠大脑缺血再灌注损伤后炎症反应的抑制作用和机制。方法：选取100只成年雄性大鼠,随机分成对照和治疗组。采用线栓方法由颈内到颈外进行插线处理,造成大脑中动脉处于闭塞状态的再灌注动物模型。治疗组颈动脉进行注射少量NRG-1β干预性治疗,通过氯化三苯基四氮唑（TTC）检查脑梗塞范围,细胞凋亡采用原住脱氧核糖核苷酸末端转移酶介导缺口末端进行标记,采用免疫组织化学、免疫荧光双标记法及免疫印迹法观察脑组织基质金属蛋白酶-9（MMP-9）表达。结果：脑缺血再灌注损伤后,随时间延长及缺氧,对照组大鼠大脑皮质和纹状体区脑组织细胞凋亡,并且胶质细胞MMP-9蛋白表达逐渐增加。治疗组大鼠经注射NRG-1β干预性治疗后,缺血脑组织梗死范围及其细胞凋亡数量相对呈明显下降趋势。胶质细胞MMP-9表达呈降低趋势。结论：大鼠脑缺血再灌注损伤后体内NRG-1β抑制胶质细胞MMP-9的表达,控制缺血脑组织梗死的范围并抑制正常细胞的凋亡,发挥了重要的抗炎作用,可作为对于大脑缺血再灌注损伤的研究新靶点。     

Neuromodulation of STDP through short-term changes in firing causality

Spike timing dependent plasticity (STDP) likely plays an important role in forming and changing connectivity patterns between neurons in our brain. In a unidirectional synaptic connection between two neurons, it uses the causal relation between spiking activity of a presynaptic input neuron and a postsynaptic output neuron to change the strength of this connection. While the nature of STDP benefits unsupervised learning of correlated inputs, any incorporation of value into the learning process needs some form of reinforcement. Chemical neuromodulators such as Dopamine or Acetylcholine are thought to signal changes between external reward and internal expectation to many brain regions, including the basal ganglia. This effect is often modelled through a direct inclusion of the level of Dopamine as a third factor into the STDP rule. While this gives the benefit of direct control over synaptic modification, it does not account for observed instantaneous effects in neuronal activity on application of Dopamine agonists. Specifically, an instant facilitation of neuronal excitability in the striatum can not be explained by the only indirect effect that dopamine-modulated STDP has on a neuron’s firing pattern. We therefore propose a model for synaptic transmission where the level of neuromodulator does not directly influence synaptic plasticity, but instead alters the relative firing causality between pre- and postsynaptic neurons. Through the direct effect on postsynaptic activity, our rule allows indirect modulation of the learning outcome even with unmodulated, two-factor STDP. However, it also does not prohibit joint operation together with three-factor STDP rules.     

Activity of neuromodulatory neurones during stepping of a single insect leg

Octopamine plays a major role in insect motor control and is released from dorsal unpaired median (DUM) neurones, a group of cells located on the dorsal midline of each ganglion. We were interested whether and how these neurones are activated during walking and chose the semi-intact walking preparation of stick insects that offers to investigate single leg-stepping movements. DUM neurones were characterized in the thoracic nerve cord by backfilling lateral nerves. These backfills revealed a population of 6-8 efferent DUM cells per thoracic segment. Mesothoracic DUM cells were subsequently recorded during middle leg stepping and characterized by intracellular staining. Seven out of eight identified individual different types of DUM neurones were efferent. Seven types except the DUMna nl2 were tonically depolarized during middle leg stepping and additional phasic depolarizations in membrane potential linked to the stance phase of the middle leg were observed. These DUM neurones were all multimodal and received depolarizing synaptic drive when the abdomen, antennae or different parts of the leg were mechanically stimulated. We never observed hyperpolarising synaptic inputs to DUM neurones. Only one type of DUM neurone, DUMna, exhibited spontaneous rhythmic activity and was unaffected by different stimuli or walking movements.     

Altering cAMP levels within a central pattern generator modifies or disrupts rhythmic motor output

Cyclic AMP is a second messenger that has been implicated in the neuromodulation of rhythmically active motor patterns. Here, we tested whether manipulating cAMP affects swim motor pattern generation in the mollusc, Tritonia diomedea. Inhibiting adenylyl cyclase (AC) with 9-cyclopentyladenine (9-CPA) slowed or stopped the swim motor pattern. Inhibiting phosphodiesterase with 3-isobutyl-1-methylxanthine (IBMX) or applying dibutyryl-cAMP (dB-cAMP) disrupted the swim motor pattern, as did iontophoresing cAMP into the central pattern generator neuron C2. Additionally, during wash-in, IBMX sometimes temporarily produced extended or spontaneous swim motor patterns. Photolysis of caged cAMP in C2 after initiation of the swim motor pattern inhibited subsequent bursting. These results suggest that cAMP levels can dynamically modulate swim motor pattern generation, possibly shaping the output of the central pattern generator on a cycle-by-cycle basis.     

Electrical stimulation of the preoptic area in Eigenmannia: evoked interruptions in the electric organ discharge

The functional role of the basal forebrain and preoptic regions in modulating the normally regular electric organ discharge was determined by focal brain stimulation in the weakly electric fish, Eigenmannia. The rostral preoptic area, which is connected with the diencephalic prepacemaker nucleus, was examined physiologically by electrical stimulation in a curarized fish. Electrical stimulation of the most rostral region of the preoptic area with trains of relatively low intensity current elicits discrete bursts of electric organ discharge interruptions in contrast to other forebrain loci. These responses were observed primarily as after-responses following the termination of the stimulus train and were relatively immune to variations in the stimulus parameters. As the duration and rate of these preoptic-evoked bursts of electric organ discharge interruptions (approximately 100 ms at 2 per s) are similar to duration and rate of natural interruptions, it is proposed that these bursts might be precursors to natural interruptions. These data suggest that the preoptic area, consistent with its role in controlling reproductive behaviors in vertebrates, may be influencing the occurrence of electric organ discharge courtship signals by either direct actions on the prepacemaker nucleus or through other regions that are connected with the diencephalic prepacemaker nucleus. Accepted: 16 October 1999     

Modulation of behavior by biogenic amines and peptides in the blue crab,Callinectes sapidus

Using the blue crab Callinectes sapidus as a model system, we have investigated the effects of potential neuromodulators on freely behaving animals. Of interest is the modulatory effect of a number of drugs on three rhythmic behaviors of the blue crab: courtship display (CD) of the male crab, sideways swimming and backward swimming. The drugs tested were proctolin, dopamine, octopamine, serotonin, and norepinephrine. Injection of each drug elicited a unique posture or combination of limb movements. These experiments showed two results pertinent to CD behavior: A posture identical to the CD posture was displayed after dopamine injection; and rhythmic leg waving similar to CD was evoked by proctolin. An unusual combination of flexion and extension of all limbs and movements of some limbs occurred after serotonin injection. Injection of octopamine led to a posture antagonistic to CD posture. The effects of these drugs were concentration- and time-dependent. Injection of dopamine, octopamine, or serotonin produced effects that were seasonally-dependent, and the influence of proctolin proved to be dependent on developmental stage. Quantitative analysis of leg waving movements after proctolin injection allowed for comparison of these movements to naturally-occurring behavior.Abbreviations CD courtship display - DA dopamine - OA octopamine - 5-HT serotonin - NE norepinephrine - PROC proctolin     

Complex behavior induced by egg-laying hormone in Aplysia

Previous studies have described a pattern of complex behavior that occurs in the marine mollusc Aplysia during egg laying. Egg laying and the behavior are initiated by a burst of impulse activity in the neuroendocrine bag cells of the abdominal ganglion or by injection of bag cell extract. To more precisely identify the factors responsible for inducing the behavior we injected animals with egg laying hormone (ELH), one of the neuropeptides secreted by the bag cells. We found that ELH causes a behavior pattern similar to what occurs during spontaneous egg laying. This includes a temporal pattern of head movements consisting of waves and undulations, followed near the beginning of egg deposition by a transition to head weaves and tamps and inhibition of locomotion. There was also a small decrease in respiratory pumping. Except for respiratory pumping, a similar pattern occurred in a second group of animals injected with atrial gland homogenate, which is presumed to induce bag cell activity, but not in controls. These results further implicate ELH in regulation of the behavior. We discuss possible sites of action of ELH and the neural mechanisms by which the behavior is controlled.Abbreviations ELH egg laying hormone - ASW artificial sea water     

Vasopressin cell groups exhibit strongly divergent responses to copulation and male-male interactions in mice

Arginine vasopressin (AVP) and its nonmammalian homolog arginine vasotocin influence social behaviors ranging from affiliation to resident-intruder aggression. Although numerous sites of action have been established for these behavioral effects, the involvement of specific AVP cell groups in the brain is poorly understood, and socially elicited Fos responses have not been quantified for many of the AVP cell groups found in rodents. Surprisingly, this includes the AVP population in the posterior part of the medial bed nucleus of the stria terminalis (BSTMP), which has been extensively implicated, albeit indirectly, in various aspects of affiliation and other social behaviors. We examined the Fos responses of eight hypothalamic and three extra-hypothalamic AVP-immunoreactive (-ir) cell groups to copulation, nonaggressive male-male interaction, and aggressive male-male interaction in both dominant and subordinate C57BL/6J mice. The BSTMP cells exhibited a response profile that was unlike all other cell groups: from a control baseline of ∼ 5% of AVP-ir neurons colocalizing with Fos, colocalization increased significantly to ∼ 12% following nonaggressive male-male interaction, and to ∼ 70% following copulation. Aggressive interactions did not increase colocalization beyond the level observed in nonaggressive male mice. These results suggest that BSTMP neurons in mice may increase AVP-Fos colocalization selectively in response to affiliation-related stimuli, similar to findings in finches. In contrast, virtually all other cell groups were responsive to negative aspects of interaction, either through elevated AVP-Fos colocalization in subordinate animals, positive correlations of AVP-Fos colocalization with bites received, and/or negative correlations of AVP-Fos colocalization with dominance. These findings greatly expand what is known of the contributions of specific brain AVP cell groups to social behavior.