迷走神经刺激对记忆的影响

迷走神经刺激(vagus nerve stimulation, VNS)用于终止癫痫发作已经有二十年的历史.期间VNS也用于难治性抑郁的治疗.在治疗过程中研究者发现VNS 对癫痫、抑郁患者的学习和记忆能力有改善作用,这种改善作用在一些动物和人体实验中也得到证实.但VNS在记忆形成的哪个阶段起作用以及如何起作用的具体机制尚不十分清楚.因此,进一步了解VNS对记忆的影响及作用机制有利于探讨记忆形成的生理机制,也为临床治疗特异性记忆障碍和相关神经精神疾病提供新的思路和有益补充.本文综述了近十几年来VNS对记忆的影响及相关机制.     

弱电刺激大鼠迷走神经中枢端在海马CA1区产生周期性theta电振荡

目的：观察弱电刺激迷走神经中枢端对正常大鼠海马细胞放电及场电的影响。方法：雄性成年大鼠45只．分离其颈部左侧迷走神经,结扎外周端,弱电（10Hz,0．5ms,1.5～5.0V,15-20／chain）刺激,每5min一次,共20串：记录右侧海马CAI细胞放电及双侧海马CAI场电。结果：双侧场电出现周期性theta电振荡（38／45,84．4％）,伴有theta—on（n=30）和theta—off（n=5）两种形式的非簇状紧张性细胞放电.结论：弱电刺激迷走神经中枢端激活海马CAI区网络,并对网络内细胞放电有紧张性调制作用.     

Controlled sinus arrhythmia during burst stimulation of the vagus nerve

In experiments on anesthesized cats and rats the desynchronization of the heart rate and burst stimulation of the vagus brought about severe sinus arrhythmia. Analysis of the functional dependence between the P--S interval (atrial wave of the ECG--moment of vagus stimulation) and the P--P interval showed periodical alterations in pacemaker sensitivity to the effect of the vagus during each cardiac cycle. It is supposed that natural vagus arrhythmia is the result of discoordination between heart automacy and efferent vagus bursts of central origin.     

The influence of electrical stimulation of vagus nerve on elemental composition of dopamine related brain structures in rats

Recent studies of Parkinson's disease indicate that dorsal motor nucleus of nerve vagus is one of the earliest brain areas affected by alpha-synuclein and Lewy bodies pathology. The influence of electrical stimulation of vagus nerve on elemental composition of dopamine related brain structures in rats is investigated. Synchrotron radiation based X-ray fluorescence was applied to the elemental micro-imaging and quantification in thin tissue sections. It was found that elements such as P, S, Cl, K, Ca, Fe, Cu, Zn, Se, Br and Rb are present in motor cortex, corpus striatum, nucleus accumbens, substantia nigra, ventral tectal area, and dorsal motor nucleus of vagus. The topographic analysis shows that macro-elements like P, S, Cl and K are highly concentrated within the fiber bundles of corpus striatum. In contrast the levels of trace elements like Fe and Zn are the lowest in these structures. It was found that statistically significant differences between the animals with electrical stimulation of vagus nerve and the control are observed in the left side of corpus striatum for P (p = 0.04), S (p = 0.02), Cl (p = 0.05), K (p = 0.02), Fe (p = 0.04) and Zn (p = 0.02). The mass fractions of these elements are increased in the group for which the electrical stimulation of vagus nerve was performed. Moreover, the contents of Ca (p = 0.02), Zn (p = 0.07) and Rb (p = 0.04) in substantia nigra of right hemisphere are found to be significantly lower in the group with stimulation of vagus nerve than in the control rats.     

Effect of electrical stimulation of the vagus on plasma motilin concentration in dog

Ten dogs anesthetized with α-chloralose were prepared with platinum monopolar electrodes in the antrum, duodenum and jejunum to record myoelectrical activity and bipolar stimulating electrodes placed on distal cut end of both cervical vagi to apply electric stimulation. Blood samples were obtained from both portal and femoral veins before and after bilateral vagal stimulation was initiated while the myoelectric activity was recorded continuously. The stimulation parameters used were low frequency (9V, 5 cps, 0.5 ms) and high frequency stimulus (9V, 30 cps, 10 ms) for 10 min. During the stimulation, plasma motilin concentrations increased significantly in both portal and femoral veins with simultaneous increases in the spike activity. The increment in the motilin level of portal venous blood was more marked. In 7 dogs, high frequency stimulation was repeated while the animals received i.v. atropine, 100 μg/kg-hr. Atropinization completely blocked the increase in the motilin concentration in response to high frequency stimulus with a simultaneous inhibition of the spike activity. The study suggests strongly that the vagus nerve plays an important role on endogenous release of motilin through its cholinergic pathway.     

Hypothalamic evoked potentials to vagus and sciatic nerve stimulation

Hypothalamic evoked potentials to stimulation of the cervical portion of the vagus nerve and the sciatic nerve were recorded in experiments on cats anesthetized with chloralose and immobilized with succinylcholine. When both monopolar and bipolar recording techniques were used the focus of maximal activity of both "visceral" and "somatic" evoked potentials was located in the supramammillary and posterolateral region of the hypothalamus. Responses in the tuberal and anterior hypothalamus occurred in most experiments after a longer latent period, their amplitude was lower, and they were less stable. Evoked potentials in the focus of maximal activity of the posterior hypothalamus are similar in all parameters to responses of the mesencephalic reticular formation. Evoked potentials to stimulation of the visceral nerve have a higher threshold of generation and a lower amplitude than the "somatic" responses and they are inhibited more strongly when the frequency of stimulation is increased. Evoked potentials arising in the hypothalamus in response to stimulation of the vagus and sciatic nerves are regarded as nonspecific responses of reticular type.L. A. Orbeli Institute of Physiology, Academy of Sciences of the Armenian SSR, Erevan. Translated from Neirofiziologiya, Vol. 5, No. 3, pp. 253–260, May–June, 1973.     

Potentiation of cholecystokinin-induced exocrine secretion by either electrical stimulation of the vagus nerve or exogenous VIP administration in the guinea pig pancreas

In the anaesthetized guinea pig, the secretory responses (pancreatic juice flow and protein output) induced by electrical stimulation of the vagus nerve were not blocked by atropine but by hexamethonium. Excitation of the left vagus nerve induced by electrical stimulation significantly potentiated the C-terminal octapeptide of cholecystokinin (CCK-OP)-induced secretory responses. In the isolated perfused pancreas of guinea pig, the secretory responses induced by CCK-OP at concentrations in the physiological range were markedly potentiated by simultaneous stimulation with vasoactive intestinal peptide (VIP). However, the secretory responses induced by CCK-OP at higher concentrations were not potentiated but inhibited by simultaneous stimulation of VIP. The secretory responses induced by carbachol (CCh) at any concentrations were not potentiated but inhibited by simultaneous stimulation of VIP. These results support the view that VIP released from the nerve endings can potentiate the hormonal action of CCK-OP.     

Canine vagus nerve stores cholecystokinin-58 and -8 but releases only cholecystokinin-8 upon electrical vagal stimulation

Cholecystokinin-58 has been shown to be the major form of cholecystokinin (CCK) released to the circulation upon lumenal stimulation of the small intestine in humans and dogs. In anesthetized dogs, electrical vagal stimulation evokes pancreatic exocrine secretion that is in part mediated through the release of CCK. We studied the molecular form of CCK stored in canine vagus nerves and that released into circulation upon electrical vagal stimulation. Gel filtration and radioimmunoassay of the water and acid extracts of canine vagus nerves indicated CCK-8 (35%) and CCK-58 (65%) as the major molecular forms in the vagus nerve. Both forms of CCK isolated from the vagal extracts were equally bioactive as the standard CCK-8 and CCK-58, respectively, in stimulation of amylase release from isolated rat pancreatic acini. Analysis of plasma collected after electrical vagal stimulation indicated that CCK-8 is the only form released into the circulation. The release of CCK-8 upon electrical vagal stimulation was not affected by application of lidocaine to the upper small intestinal mucosa, suggesting that it was released from vagal nerve terminals.     

c-fos expression in trigeminal spinal nucleus after electrical stimulation of the hypoglossal nerve in the rat

The expression of the immediate early gene, c-fos, was used to determine the distribution of brainstem neurons activated by stimulation of the distal hypoglossal nerve (XIIn) trunk. The traditional view of the XIIn is one of purely motor function; however, stimulation of XIIn excites neurons in the trigeminal spinal nucleus. The rationale for this study was to use c-fos expression as a marker for postsynaptic activity to define the pattern of brainstem neurons excited by XIIn stimulation. It was further hypothesized that if the afferent fibers that course within XIIn supply deep lingual tissues, then c-fos expression after direct stimulation of XIIn should display a pattern similar to that seen after chemical irritant stimulation of the deep tongue muscle. In barbiturate-anesthetized male rats electrical stimulation of XIIn produced a significant increase in Fos-positive neurons in the dorsal paratrigeminal nucleus (dPa5) and laminae I-II of caudal subnucleus caudalis (Vc) and upper cervical dorsal horn. Mustard oil injection into the deep tongue muscle also produced an increase in c-fos expression in dPa5; however, the highest density of expression occurred in laminae I-II at the dorsomedial aspect of rostral Vc. Both electrical stimulation of XIIn and mustard oil stimulation of the deep tongue increased c-fos expression in the caudal ventrolateral medulla, an autonomic relay nucleus. These results suggest that one site of innervation for afferent fibers that travel within the distal trunk of XIIn is to supply the deep tongue muscle and to terminate in the dPa5. A second group of postsynaptic neurons activated only by XIIn stimulation was located in lamina I-II in caudal portions of Vc and upper cervical dorsal horn, a laminar distribution consistent with a role for XIIn afferents in sensory or autonomic aspects of lingual function.     

c-fos expression in trigeminal spinal nucleus after electrical stimulation of the hypoglossal nerve in the rat

The expression of the immediate early gene, c-fos, was used to determine the distribution of brainstem neurons activated by stimulation of the distal hypoglossal nerve (XIIn) trunk. The traditional view of the XIIn is one of purely motor function; however, stimulation of XIIn excites neurons in the trigeminal spinal nucleus. The rationale for this study was to use c-fos expression as a marker for postsynaptic activity to define the pattern of brainstem neurons excited by XIIn stimulation. It was further hypothesized that if the afferent fibers that course within XIIn supply deep lingual tissues, then c-fos expression after direct stimulation of XIIn should display a pattern similar to that seen after chemical irritant stimulation of the deep tongue muscle. In barbiturate-anesthetized male rats electrical stimulation of XIIn produced a significant increase in Fospositive neurons in the dorsal paratrigeminal nucleus (dPa5) and laminae I-II of caudal subnucleus caudalis (Vc) and upper cervical dorsal horn. Mustard oil injection into the deep tongue muscle also produced an increase in c-fos expression in dPa5; however, the highest density of expression occurred in laminae I-II at the dorsomedial aspect of rostral Vc. Both electrical stimulation of XIIn and mustard oil stimulation of the deep tongue increased c-fos expression in the caudal ventrolateral medulla, an autonomic relay nucleus. These results suggest that one site of innervation for afferent fibers that travel within the distal trunk of XIIn is to supply the deep tongue muscle and to terminate in the dPa5. A second group of postsynaptic neurons activated only by XIIn stimulation was located in lamina I-II in caudal portions of Vc and upper cervical dorsal horn, a laminar distribution consistent with a role for XIIn afferents in sensory or autonomic aspects of lingual function.     

Control of cardiac rhythm by stimulation of the vagus nerve in bursts in the rat

Burst stimulation of the vagus nerve in rats made it possible to obtain the ranges of the heart rate regulation. The increase of the number of impulses in a burst from 1 to 16 leads to a consistent decrease in the range of regulation from respectively 72.1 and 66.7% to 30.4 and 25% of the initial rate. The maximal range (10.1% of the initial rate) is reached with 4 impulses in a burst. The phenomenon of the regulation is reversed by atropine.     

Sensitive control of heart rate in monkeys using burst stimulation of the vagus nerve

Burst vagus stimulation led to synchronization of the cardiac and vagal rhythms at certain frequency ranges. The increase of the number of impulses in a burst from 1 to 16 extended the range of synchronization and shifted it towards lower frequencies forming a total range of exact regulation of the heart rate within 85--40% of the initial rate. It was suggested that vagal effect consists of tonic and synchronizing components.     

The spectrogram of heart rate in cats following burst stimulation of the vagus nerve

Denervation of the heart (bilateral vagotomy and propranolol) in artificially ventilated cats didn't remove respiratory peaks on the spectrogram of heart rate, while burst stimulation of vagus nerve increased or decreased them several times by synchronization of the heart and vagus rhythms, which in its turn was observed under the bradycardia only. At the same time, the desynchronization of rhythms provoked severe sinus arrhythmia which had a distinct periodic character. Under these conditions, there were high non-respiratory peaks appearing at the spectrogram of the heart rate that indicated existence of two vagus chronotropic effects: a well known tonic one and special intracycle synchronizing effect correcting duration of every cardiac cycle.