The facilitatory influence of anterior cingulate cortex on ON-OFF response of tactile neuron in thalamic ventrobasal nucleus

The structures of limbic system have been found to modulate the auditory, visual and pain afferent signals in the related nuclei of thalamus. One of those structures is anterior cingulate cortex (ACC) that influences nocuous response of the pain-sensitive neurons in the ventropostero-lateral nucleus of thalamus. Thus, we inferred that ACC would also modulate tactile information at the thalamic level. To test this assumption, single units were recorded extracellularly from thalamic ventrobasal nucleus (VB). Tactile ON-OFF response and the relationship between different patterns of the responses and the parameters of tactile stimulation were examined. Furthermore, the influence of ACC on the tactile ON-OFF response was studied. ACC stimulation was found to produce a facilitatory effect on the OFF-response of ON-OFF neurons. It lowered the threshold of the off-response of that neuron, and therefore changed the response pattern or enhanced the firing rate of the OFF-response of the neuron. The study on receptive fields of ON-OFF neurons showed that the excitation of the ACC could change an ON-response on the verge of a receptive field into an ON-OFF response. The above results suggest that the ACC modulation sharpens the response of a VB neuron to a moving stimulus within its receptive field, indicating that the limbic system can modulate tactile ascending sensory information.     

The facilitatory influence of anterior cingulate cortex on ON-OFF response of tactile neuron in thalamic ventrobasal nucleus

The structures of limbic system have been found to modulate the auditory, visual and pain afferent signals in the related nuclei of thalamus. One of those structures is anterior cingulate cortex (ACC) that influences nocuous response of the pain-sensitive neurons in the ventropos-tero-lateral nucleus of thalamus. Thus, we inferred that ACC would also modulate tactile information at the thalamic level. To test this assumption, single units were recorded extracellularly from thalamic ventrobasal nucleus (VB). Tactile ON-OFF response and the relationship between different patterns of the responses and the parameters of tactile stimulation were examined. Furthermore, the influence of ACC on the tactile ON-OFF response was studied. ACC stimulation was found to produce a facilitatory effect on the OFF-response of ON-OFF neurons. It lowered the threshold of the off-response of that neuron, and therefore changed the response pattern or enhanced the firing rate of the OFF-response of the neuron. The study on rec     

Depolarization of primary afferents during fictitious scratching in thalamic cats

The dorsal cord and dorsal root potentials were recorded in immobilized thalamic cats during fictitious scratching evoked by mechanical stimulation of the ear. Depolarization of primary afferents was shown to be simulated by the central scratching generator. Antidromic spike discharges appeared at the peak of the primary afferent depolarization waves in certain afferent fibers. Similar discharges arise in the resting state in response to stimulation of limb mechanoreceptors. It is suggested that during real scratching primary afferent depolarization and antidromic spikes evoked by it may effectively modulate the level of the afferent flow to spinal neurons.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 10, No. 2, pp. 173–176, March–April, 1978.     

刺激兔丘脑不同核团和胼胝体引起的膈神经放电效应

实验在33例清醒、肌肉麻痹和切断双侧迷走神经的家兔上进行,观察了刺激丘脑不同核团(VIL,VL,VPM 和 MI)和胼胝体纤维以激活皮层时膈神经的放电效应。当在吸气相(膈神经放电时)给予上述核团及胼胝体纤维电脉冲刺激,可使膈神经放电短暂抑制,随后的呼气相缩短、吸气相提前出现。如果在呼气相刺激上述核团,也能使该呼气时相缩短,随后的吸气时相提前出现。当在皮层接受 VL 投射的局部区域给予回苏灵后,再刺激 VL,皮层诱发电位增大,除使原先的膈神经放电效应更为明显外,还可在呼气相刺激时引起膈神经即刻的短暂放电。以上实验结果提示,当用回苏灵使皮层活动加强后,刺激丘脑 VL 引起的膈神经放电效应明显增强。损毁红核或切断皮层下行传导束但保留皮层脊髓束后,刺激丘脑引起的膈神经放电效应均不受影响,表明传入冲动激活皮层后引起的膈神经放电效应可能主要经皮层脊髓束下传,而皮层红核脊髓束不起重要作用。     

糖尿病痛过敏大鼠尾神经中传入单位对交感传出的反应

实验观察了刺激交感神经（sympathetic stimulation,SS）、静脉注射去甲肾上素（noradrenaline,NA）和酚妥拉明对糖尿病痛过敏大鼠尾神经中各种传入单位的影响。结果发现,糖尿病痛过敏大鼠的具有自发放电的C单位和Aδ单位在SS后放电频率增加,α－受体阻断剂能消除这些自发放电活动;在无自发放电的C单位和Aδ单位中,SS能使部分C单位和Aδ单位由静息状态转入活动状态;它虽不能诱发C－机械感受单位（C mechanical receptive unit,C-M）产生传入放电,但可诱发部分C－机械热单位（C mechano-heat unit,C-MH）和C－多型单位（C polymodal unit,C-Pol）的活动;SS还能使部分Aδ－机械单位（Aδ mechanical receptive unit,Aδ-M）和Aδ－机械热单位（Aδ mechano-heat unit,Aδ-MH）产生传入放电;它所诱发的C单位和Aδ单位反应的潜伏期不等,但不短于5s;SS不能引起糖尿病痛过敏大鼠Aβ机械感受性单位和对照组大鼠各类感受性单位产生新的传入活动。静脉注射NA可诱发糖尿病痛过敏大鼠的部分C单位和Aδ单位产生新的传入活动。结果提示,交感神经末梢释放的NA对糖尿病痛过敏大鼠C单位和Aδ单位的兴奋作用是糖尿病大鼠产生痛过敏和感觉异常的外周因素。     

Somatosympathetic reflex in rats with various models of arterial hypertension

Spontaneous and reflex activities of sympathetic nerve were compared in animals with arterial hypertension of different aetiology. Reflex discharges elicited by single-shock stimulation of afferent fibres were recorded. In acute experiences on anaesthetized rats with renovascular and spontaneous (SHR) model of arterial hypertension, electric basal and evoked activity (somatosympathetic reflex) in cervical sympathetic trunk were recorded. It is shown, that the spontaneous electric activity in sympathetic nerve of hypertensive rats is larger than spontaneous activity of normotensive control animals. The somatosympathetic reflex in hypertensive rats differs from that of control animals. In rats with renovascular model of hypertension, the reflex magnitude is reduced, and in the SHR the reflex is increased. Time characteristics of the reflex in hypertensive rats differed among them. It is suggested that functional activities of the brain stem in rats with different arterial hypertension model are unequal.     

Relationship between functional characteristics of cat visual cortex neurons,their response to novelty,and short-term memory

In the visual cortex of unanesthetized cats, the number and frequency of discharges in response to a new stimulus differed from the subsequent responses: the first response was more intensive in 34% of the neurons, but in 30% it was inhibited. The phenomenon of short-term memory was detected in 19% of the cells: it was expressed in regeneration of the configuration of response discharges after the cessation of rhythmic stimulation. These peculiarities can be linked with functional organization of the neurons. We divided them into two groups according to their response to photic stimuli. The first group includes short-latent neurons that respond with discharges of the phasic type and that virtually or totally lack spontaneous activity. The second group consists of long-latent neurons with the tonic type of discharges and distinct spontaneous activity. In the overwhelming majority of cases, response to novelty and short-term memory were discovered in neurons of the second group. It is hypothesized that the population of neurons of the first group — having narrower afferent connections — takes part mainly in analysis of properties of a photic stimulus; the population of neurons of the second group participates in information processing at the final and highest level, on which mechanisms of memory and attention are implicated.Institute of Higher Nervous Activity and Neurophysiology, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 2, No. 6, pp. 611–617, November–December, 1970.     

Study of tonic and evoked electrical activity in efferent fibers of the sympathetic nerve in white rats

In anaesthetised Wistar rats, electrical sympathetic activity and a somatosympathetic reflex in the cervical sympathetic trunk elicited by a single electrical shock to forelimb or hindlimb afferent nerves, were recorded. The spontaneous activity was shown to conform with the pulse and respiratory waves of arterial pressure. Somatosympathetic reflex consists of early and late discharges evoked by somatic myelinated afferent fibres stimulation, and C-response elicited by stimulation of unmyelinated afferent fibres in spinal nerves.     

The binding problem in population neurodynamics: a network model for stimulus-specific coherent oscillations

A hypothesis is presented that coherent oscillatory discharges of spatially distributed neuronal groups (the supposed binding mechanism) are the result of the convergence of stimulus-dependent activity in modality-specific afferent pathways with oscillatory activity generated in unspecific sensory systems. This view is supported by simulation experiments on model networks.     

Differential effects of methylphenidate and cocaine on GABA transmission in sensory thalamic nuclei

Methylphenidate (MPH) is widely used to treat children and adolescents diagnosed with attention deficit/hyperactivity disorder. Although MPH shares mechanistic similarities to cocaine, its effects on GABAergic transmission in sensory thalamic nuclei are unknown. Our objective was to compare cocaine and MPH effects on GABAergic projections between thalamic reticular and ventrobasal (VB) nuclei. Mice (P18‐30) were subjected to binge‐like cocaine and MPH acute and sub‐chronic administrations. Cocaine and MPH enhanced hyperlocomotion, although sub‐chronic cocaine‐mediated effects were stronger than MPH effects. Cocaine and MPH sub‐chronic administration altered paired‐pulse and spontaneous GABAergic input differently. The effects of cocaine on evoked paired‐pulse GABA‐mediated currents changed from depression to facilitation with the duration of the protocols used, while MPH induced a constant increase throughout the administration protocols. Thalamic reticular nucleus GAD67 and VB Ca_V3.1 protein levels were measured using western blot to better understand their link to increased GABA release. Both proteins were increased by sub‐chronic administration of cocaine. MPH showed effects on GABAergic transmission that seems less disruptive than cocaine. Unique effects of cocaine on postsynaptic VB calcium currents might explain deleterious cocaine effects on sensory thalamic nuclei. These results suggest that cocaine and MPH produced distinct presynaptic alterations on GABAergic transmission.     

Is there a thalamic component to experience-dependent cortical plasticity?

Sensory deprivation and injury to the peripheral nervous system both induce plasticity in the somatosensory system of adult animals, but in different places. While injury induces plasticity at several locations within the ascending somatosensory pathways, sensory deprivation appears only to affect the somatosensory cortex. Experiments have been performed to detect experience-dependent plasticity in thalamic receptive fields, thalamic domain sizes and convergence of thalamic receptive fields onto cortical cells. So far, plasticity has not been detected with sensory deprivation paradigms that cause substantial cortical plasticity. Part of the reason for the lack of thalamic plasticity may lie in the synaptic properties of afferent systems to the thalamus. A second factor may lie in the differences in the organization of cortical and thalamic circuits. Many deprivation paradigms induce plasticity by decreasing phasic lateral inhibition. Since lateral inhibition appears to be far weaker in the thalamus than the cortex, sensory deprivation may not cause large enough imbalances in thalamic activity to induce plasticity in the thalamus.     

Thalamic stimulation for control of movement disorders

Chronic recurrent thalamic stimulation has been effective in alleviating a variety of movement disorders. In contrast to thalamic lesions, it is preferred for the treatment of intractable motor disorders in low-risk elderly patients and patients with diffuse brain lesions secondary to trauma. Abnormal diencephalic electrical discharges have been observed and thought to be associated, in some way, with either generating or sustaining the movement abnormalities. The beneficial effects are ascribed to an electrophysiologic functional ablation of the discharging systems. This interpretation is based on the observation that the diencephalic discharges are attenuated by the applied stimulation and that the beneficial effects are reversible even after several months of applied therapeutic stimulation.     

Properties of monosynaptic connections between callosal neurons and specific thalamic nuclei

A comparative analysis of monosynaptic afferent and efferent connections of callosal neurons and target neurons of transcallosal fibers with neurons of the specific ipsilateral thalamic nuclei (ventral posterolateral, ventral posteromedial, ventral lateral, and anteroventral) was undertaken on the sensomotor cortex of unanesthetized rabbits, using an electrophysiological method. Differences were demonstrated between callosal neurons and target neurons of transcallosal fibers with respect to monosynaptic inputs from the thalamic nuclei and pathways proceeding toward these structures and (or) entering the pyramidal tract. Among target neurons, compared with callosal neurons, more cells had descending projections (54 and 14%, respectively). Monosynaptic action potentials arose in 22% of target neurons in response to stimulation of specific thalamic nuclei, whereas no such responses occurred in callosal neurons. Projections of target neurons into thalamic nuclei were shown to be formed both by independent fibers and by axon collaterals of the pyramidal tract. It is postulated that the distinctive properties thus discovered indicate significantly greater convergence of influence of thalamic relay neurons on the target neurons; this determines differences known to exist in characteristics of receptive fields and spontaneous and evoked activity of callosal neurons, on the one hand, and of neurons excited synaptically by transcallosal stimulation, on the other hand.Institute of Higher Nervous Activity and Neurophysiology, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 17, No. 3, pp. 305–314, May–June, 1985.     

Principle of neuronal organization of defensive reflexes in mollusks

Spontaneous and evoked synaptic activity of command neurons for the defensive response of spiracle closing were studied by simultaneous intracellular recording of activity of several identified CNS neurons in snails. Comparison of monosynaptic EPSPs in command neurons evoked by discharges of presynaptic neurons with spontaneous synaptic potentials indicated that the central organization of the defensive reflex is in the form of a two-layered neuron net in which each neuron of the afferent layer possesses a local receptive field, but which overlaps with other afferent neurons. Each neuron of the afferent layer is connected with each neuron of the efferent layer by monosynaptic excitatory connections that differ in efficiency (maximal only with one neuron of the efferent layer). Both receptive fields of neurons of the afferent layer and "fields of efficiency of synaptic connections" are distributed according to the normal law. As a result of this organization the neuron net acquires a new quality: The action of different stimuli leads to the appearance of differently located "spatial excitation profiles" of efferent layer neurons even when this action of the stimulus occurs not at the center of the receptive field.Institute of Higher Nervous Activity and Neurophysiology, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 16, No. 1, pp. 26–34, January-February, 1984.     

Activity of lumbar interneurons during late long-lasting discharges in motor nerves of immobilized thalamic cats

Activity of lumbar spinal neurons was recorded extracellularly during late long-lasting discharges in efferent nerves in immobilized thalamic cats. Of the total number of cells tested, 70% changed their activity during late discharges. The activity of 35% of neurons was increased during late discharges in nerves to flexors, but inhibited during discharges in nerves to extensors. Responses of 27% of neurons were of the opposite character. Other neurons were found whose activity was increased (5%) and reduced (3%), respectively, during later discharges in both flexor and extensor nerves. Most interneurons which changed their activity during late discharges were located in lateral parts of the intermediate zone of gray matter and the ventral horn at a depth of 2.8 mm. The character of the afferent input to a neuron was found to depend on the late efferent discharges and activity of the neurons correlated with them. Neurons whose activity was unchanged during late discharges (30%) were mainly located rather more dorsally, at a depth of about 2.0 mm. The possible mechanisms of the participation of these groups of interneurons in the generation of late discharges are discussed.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 11, No. 3, pp. 236–244, May–June, 1979.     

Recent evidence for activity-dependent initiation of sympathetic sprouting and neuropathic pain

Traumatic injury or inflammatory irritation of the peripheral nervous system often leads to persistent pathophysiological pain states. It has been well-documented that, after peripheral nerve injury or inflammation, functional and anatomical alterations sweep over the entire peripheral nervous system including the peripheral nerve endings, the injured or inflamed afferent fibers, the dorsal root ganglion (DRG), and the central afferent terminals in the spinal cord. Among all the changes, ectopic discharge or spontaneous activity of primary sensory neurons is of great clinical interest, as such discharges doubtless contribute to the develop-ment of pathological pain states such as neuropathic pain. Two key sources of abnormal spontaneous activity have been identified following peripheral nerve injury: the injured afferent fibers (neuroma) leading to the DRG, and the DRG somata. The purpose of this review is to provide a global account of the abnormal spontaneous activity in various animal models of pain. Particular attention is focused on the consequence of peripheral nerve injury and localized inflammation. Further, mechanisms involved in the generation of spontaneous activity are also reviewed; evidence of spontaneous activity in contributing to abnormal sympathetic sprouting in the axotomized DRG and to the initiation of neuropathic pain based on new findings from our research group are discussed. An improved understanding of the causes of spontaneous activity and the origins of neuropathic pain should facilitate the development of novel strategies for effective treatment of pathological pain.     

肾动脉内注射腺苷兴奋肾神经传入纤维的自发活动

应用记录肾神经传入纤维多单位和单位放电的方法,观察肾动脉内注射腺苷对麻醉家兔肾神经传入纤维自发放电活动的影响。结果表明：(1)肾动脉内注射50,100和200nmol／kg腺苷可呈剂量依赖性地兴奋肾神经传入纤维的活动,而动脉血压不变。(2)肾动脉内预先应用选择性腺苷A1受体阻断剂DPCPX(160nmol/kg),可部分阻断腺苷对肾神经传入纤维的兴奋作用。(3)静脉应用一氧化氮合酶抑制剂L-NAME(0．1mmol／kg)预处理,延长并增强了肾神经传入纤维对腺苷的反应。以上结果提示,肾动脉内应用腺苷可兴奋肾传入纤维的自发放电活动,一氧化氮作为抑制性因素参与腺苷诱导的肾神经传入纤维兴奋。     

Regional specificity of functional sensory connections in developing spinal cord cultures varies with the incidence of spontaneous bioelectric activity

Summary Cultured spinal cord explants in which little spontaneous bioelectric activity was present showed, when monitored using sensory ganglion-evoked monosynaptic action potentials, diffuse innervation by ingrowing afferent fibers at 3–4 weeks in vitro. In contrast, highly active cultures of the same age showed a strong tendency for functional sensory connections to be made within the dorsal half of the cord. Regional specificity was present in mature cultures (4–5 weeks in vitro), however, even when their spontaneous activity level was low. The results support earlier results using tetrodotoxin, and make it appear likely that centrally generated neuronal discharges can influence the topography of afferent terminals within the developing spinal cord.     

Antidromic discharges of dorsal root afferents in the neonatal rat.

Presynaptic inhibition of primary afferents can be evoked from at least three sources in the adult animal: 1) by stimulation of several supraspinal structures; 2) by spinal reflex action from sensory inputs; or 3) by the activity of spinal locomotor networks. The depolarisation in the intraspinal afferent terminals which is due, at least partly, to the activation of GABA(A) receptors may be large enough to reach firing threshold and evoke action potentials that are antidromically conducted into peripheral nerves. Little is known about the development of presynaptic inhibition and its supraspinal control during ontogeny. This article, reviewing recent experiments performed on the in vitro brainstem/spinal cord preparation of the neonatal rat, demonstrates that a similar organisation is present, to some extent, in the new-born rat. A spontaneous activity consisting of antidromic discharges can be recorded from lumbar dorsal roots. The discharges are generated by the underlying afferent terminal depolarizations reaching firing threshold. The number of antidromic action potentials increases significantly in saline solution with chloride concentration reduced to 50% of control. Bath application of the GABA(A) receptor antagonist, bicuculline (5-10 microM) blocks the antidromic discharges almost completely. Dorsal root discharges are therefore triggered by chloride-dependent GABA(A) receptor-mediated mechanisms; 1) activation of descending pathways by stimulation delivered to the ventral funiculus (VF) of the spinal cord at the C1 level; 2) activation of sensory inputs by stimulation of a neighbouring dorsal root; or 3) pharmacological activation of the central pattern generators for locomotion evokes antidromic discharges in dorsal roots. VF stimulation also inhibited the response to dorsal root stimulation. The time course of this inhibition overlapped with that of the dorsal root discharge suggesting that part of the inhibition of the monosynaptic reflex may be exerted at a presynaptic level. The existence of GABA(A) receptor-independent mechanisms and the roles of the antidromic discharges in the neonatal rat are discussed.     

The cortico-thalamic theory for generalised spike-wave discharges

The origin of generalized absence epilepsy is still not known. In the last century, four theories have dominated the debate about the origin of the bilateral synchronous generalized spike-wave discharges associated with absence seizures: the "centrencephalic" theory [Penfield and Jasper], the "cortical" [Bancaud, Niedermeyer, Luders], the "cortico-reticular" theory [Gloor, Kostop[oulos, Avoli] and the "thalamic clock" theory [Buzsaki]. There is now some evidence that absence epilepsy, as studied in the WAG/Rij model, is a corticothalamic type of epilepsy. A new hypothesis is proposed which suggests that a cortical focus in the somatosensory cortex is driving the widespread corticothalamic networks during spontaneous absence seizures. This modern theory was given the name "hot spot' theory" [Meeren et al., 2002]. According to the present view three brain structures are critically involved and their integrity seems a minimal and sufficient condition for the occurrence of spike-wave discharges. Firstly, the reticular thalamic nucleus is involved and most likely its rostral pole. Secondly, the thalamocortical relay cells in the ventrobasal complex play a role and, thirdly and most importantly, the cerebral cortex with its epileptic zone. The zone in which the epileptic focus seems to be localised is located on the somato-sensory cortex, and more precisely in the area on which the peri-oral region including the upper lip, projects.