Cortical Influences on Neurons of the Lateral Reticular Nucleus Responding to Noxious Stimuli

The effect of frontoparietal sensorimotor (FPSM) cortex stimulation on both the spontaneous and the noxious evoked activity of neurons in the lateral reticular nucleus (LRN) was tested in barbiturate-anesthetized rats. Ninety-three LRN neurons that responded to a noxious heat stimulus (HS) were recorded (72% antidromically fired from the cerebellum). Of these, 66 neurons altered their spontaneous firing rates in response to cortical stimulation. Two patterns of responses were found: either an excitation followed by a suppression of spontaneous activity (52 neurons), or a pure suppression of spontaneous activity lasting 50-400 msec (14 neurons). In 46 of these neurons, it was found that cortical stimulation reduced HS-evoked activity to near the baseline level. Furthermore, it was found that when applied after a prolonged cortical stimulation, the HS was ineffective. It is concluded that FPSM cortex can influence nociceptive information in LRN neurons that respond to its stimulation, possibly interfering with the mechanisms underlying stimulation-produced analgesia (SPA). In this context, it is proposed that the cortex can modulate the activity of LRN neurons that activate, through local loops, a descending antinociceptive system and also a separate projection system to the cerebellum.     

Spontaneous and evoked activities of interpositus nucleus neurons before and after lesion of the cerebellar cortex

Spontaneous and evoked activities of nucleus interpositus neurons (IN) of the cerebellum were examined before and after cerebellar paravermal cortex lesions in cats anesthetized with alpha-chloralose. It was found that spontaneous activity increased dramatically following cortical ablation: before the lesion only 4% of cells encountered fired at a rate exceeding 80 impulses/sec., whereas up to 40% discharged at this rate postoperatively. Responses to paw stimulation were also altered: the initial excitation was lengthened from 8.5 to 15.8 msec; narrow; trough causing segmentation in this excitation, which seems to result from Purkinje cell inhibition, was absent; and the succeeding inhibitory period was reduced in duration by 50%. Also after the lesion there was a strong tendency for the neurons to discharge in bursts. It is suggested that changes in cell activity in the IN following cortical lesion unveil neural mechanisms of motor disturbances in lesioned cats.     

Effect of the vermian cortex of the anterior lobe of the cerebellum on the background electrical activity of fastigial neurons

The effect of electrical stimulation of the vermian cortex of the anterior lobe of the cerebellum on the activity of neurons of different portions of the fastigial nucleus was studied in acute experiments on cats under light nembutal anesthesia. Inhibitory influences of the cortex (80.6% of the reacting neurons) were manifested in total blocking or decrease in the frequency of the background activity of the neurons and were characterized by a long aftereffect and "rebound." Stimulation of the cortex also had a blocking effect on the inhibitory interaction of adjacent nuclear elements. Facilitatory influences (14.5% of the neurons) were expressed either by an increase of spontaneous discharges of the neurons or by the appearance of activity in rhythm with the stimulation. The effectiveness of cortical stimulation depended on the localization of the stimulating electrodes. Zones of maximum density of projections to a given neuron of the nucleus and convergence and divergence of influences were found in the cerebellar cortex.L. A. Orbeli Institute of Physiology, Academy of Sciences of the Armenian SSR, Erevan. Translated from Neirofiziolgiya, Vol. 2, No. 3, pp. 260–268, May–June, 1970.     

Effects of stimulus duration on neuronal response properties in the somatosensory cortex of the star-nosed mole

Star-nosed moles have a series of mechanosensory appendages surrounding each nostril. Each appendage is covered with sensory organs (Eimer's organs) containing both rapidly adapting and slowly adapting mechanoreceptors and each appendage is represented in primary somatosensory cortex (S1) by a single cortical module. When the skin surface of an appendage is depressed, neurons in the corresponding module in S1 respond in either a transient or sustained fashion. The aim of this study was to characterize and compare the responses of these two classes of neurons to both short (5 or 20 ms) and long (500 ms) mechanosensory stimulation. Activity from neurons in the representation of appendage 11, the somatosensory fovea, was recorded while delivering mechanosensory stimuli to the corresponding skin surface. Transient and sustained neurons had different levels of spontaneous activity and different responses to both short and long mechanosensory stimulation. Neurons with sustained responses had a significantly higher spontaneous firing rate than neurons with transient responses. Transient neurons responded to a 5 ms stimulus with excitation followed by suppression of discharge whereas sustained neurons did not exhibit post-excitatory suppression. Rather, responses of sustained neurons to 5 ms stimuli lasted several hundred milliseconds. Consequently sustained responses contained significantly more spikes than transient responses. These experiments suggest contact to the appendages causes two distinct firing patterns in cortex regardless of the duration of the stimulus. The sustained and transient responses could reflect either the activity of fundamentally different classes of neurons or activity in distinct subcortical and cortical networks.     

The modulation of sensory transmission through the medullary dorsal horn during cortically driven mastication

During mastication, reflexes are modulated and sensory transmission is altered in interneurons and ascending pathways of the rostral trigeminal sensory complex. The current experiment examines the modulation of sensory transmission through the most caudal part of the trigeminal sensory system, the medullary dorsal horn, during fictive mastication produced by cortical stimulation. Extracellular single unit activity was recorded from the medullary dorsal horn, and multiple unit activity was recorded from the trigeminal motor nucleus in anesthetized, paralyzed rabbits. The masticatory area of sensorimotor cortex was stimulated to produce rhythmic activity in the trigeminal motor nucleus (fictive mastication). Activity in the dorsal horn was compared in the presence and absence of cortical stimulation. Fifty-two percent of neurons classified as low threshold and 83% of neurons receiving noxious inputs were influenced by cortical stimulation. The cortical effects were mainly inhibitory, but 21% of wide dynamic range and 6% of low threshold cells were excited by cortical stimulation. The modulation produced by cortical stimulation, whether inhibitory or excitatory, was not phasically related to the masticatory cycle. It is likely that, when masticatory movements are commanded by the sensorimotor cortex, the program includes tonic changes in sensory transmission through the medullary dorsal horn.     

Facilitating action of medial prefrontal cortex upon the noxious thermally-evoked responses in thalamic centralis lateralis nucleus.

This paper shows a medial prefrontal cortex (CxAP9) facilitating influence upon the unit activity of the centralis lateralis (Cl) nucleus of the thalamus, in rats anesthetized with urethane. Cortical influences were studied using both cortical cooling and cortical spreading depression (CSD) procedures. Both spontaneous and noxious thermally evoked activities were considered. When CSD was propagated and affected the CxAP9, as well as during the cooling of this area, both spontaneous activity and the responses evoked in Cl cells by noxious stimulation were blocked. This effect was interpreted as a cortical disfacilitation upon Cl cells. During the cortical silent period we tested the excitability of a few Cl cells, provoking their activation by passing electrical current across the same Cl recording electrode. No changes were observed in their excitable response threshold during CSD or cortical cooling. Our results are in agreement with the proposition of a tonic cortical facilitatory action upon the spontaneous and noxious-evoked responses recorded in the Cl cells.     

Density of Sgt1-immunopositive neurons is decreased in the cerebral cortex of Alzheimer's disease brain

Sgt1 was discovered as a protein required for the mitotic activity of kinetochore and for the activity of ubiquitin ligase in yeast [Kitagawa, K., Skowyra, D., Elledge, S.J., Harper, J.W., Hieter, P., 1999. SGT1 encodes an essential component of the yeast kinetochore assembly pathway and a novel subunit of the SCF ubiquitin ligase complex. Mol. Cell 4, 21-33.]. Later, Sgt1 was identified in different organisms including mammals where it was found at high level in the brain. To understand Sgt1 function in this tissue we analyzed its localization in human brain by immunohistochemistry. In normal brain we observed Sgt1-immunostaining in Purkinje cells of the cerebellum, in granule cells of the dentate gyrus of the hippocampus and in multiple neurons of the cortex. By Western blotting we found a higher level of this protein in the cortex than in the cerebellum. Subsequent morphometric analyses showed that the density of Sgt1-immunopositive neurons varied in different cortical regions. The highest density of Sgt1-immunopositive cells was seen in the temporal cortex (from 1.2% to 5.7%), and the lowest - in the entorhinal cortex (from 0 to 1.1% of all neurons). We next compared the density of Sgt1-immunopositive neurons in cortical layers of healthy aged and Alzheimer's disease (AD) brain sections. A significant decrease in Sgt1-immunopositive neurons was found in the temporal (up to 25-fold), angular (up to 11-fold) and posterior cingulate cortex (up to five-fold). In the entorhinal and precentral cortex the reduction of Sgt1-immunopositive neurons was only about two-fold in AD brains as compared to healthy aged ones. The presence of Sgt1 in post-mitotic neurons indicates the involvement of this protein in a process different from that required for activity of the kinetochore. Decreased immunostaining in AD cortex point to Sgt1 as a possible marker of neurons degenerating in AD.     

电刺激家兔大脑皮层感觉区对丘脑束旁核痛敏单位放电活动的影响

本工作目的在于探讨大脑皮层与丘脑束旁核痛觉信息活动之间的关系。用玻璃微电极记录了60只清醒麻痹状态下家兔束旁核痛敏单位的诱发放电活动。按其对外周伤害性刺激的反应型式而分成两类,分别称为痛兴奋单位和痛抑制单位。观察到在电刺激大脑皮层感觉区时,多数痛兴奋单位呈抑制性改变,并且有时施予皮层的每一单个刺激均能立即遏止一阵痛放电,少数呈易化性改变;痛抑制单位则对伤害性刺激呈现抑制反应解除,而施予皮层的每一单个刺激均可使之先有一阵短暂的放电,然后出现抑制的现象。本组实验观察过程,完整的总例数共32个单位,包括25个痛兴奋单位(18个呈抑制改变,7个呈易化改变)和7个痛抑制单位(全部呈易化改变)。实验结果表明,大脑皮层感觉区传出系统对机体的痛觉信息传递活动具有下行调制作用。由于皮层刺激对束旁核放电的影响是逐渐发展起耒的,因此考虑在上述过程中可能有体液因素的参与。     

Spike suppression in a local cortical circuit induced by transcranial magnetic stimulation

Transcranial magnetic stimulation (TMS) noninvasively interferes with human cortical function, and is widely used as an effective technique for probing causal links between neural activity and cognitive function. However, the physiological mechanisms underlying TMS-induced effects on neural activity remain unclear. We examined the mechanism by which TMS disrupts neural activity in a local circuit in early visual cortex using a computational model consisting of conductance-based spiking neurons with excitatory and inhibitory synaptic connections. We found that single-pulse TMS suppressed spiking activity in a local circuit model, disrupting the population response. Spike suppression was observed when TMS was applied to the local circuit within a limited time window after the local circuit received sensory afferent input, as observed in experiments investigating suppression of visual perception with TMS targeting early visual cortex. Quantitative analyses revealed that the magnitude of suppression was significantly larger for synaptically-connected neurons than for isolated individual neurons, suggesting that intracortical inhibitory synaptic coupling also plays an important role in TMS-induced suppression. A conventional local circuit model of early visual cortex explained only the early period of visual suppression observed in experiments. However, models either involving strong recurrent excitatory synaptic connections or sustained excitatory input were able to reproduce the late period of visual suppression. These results suggest that TMS targeting early visual cortex disrupts functionally distinct neural signals, possibly corresponding to feedforward and recurrent information processing, by imposing inhibitory effects through intracortical inhibitory synaptic connections.     

Membrane potential synchrony in primary visual cortex during sensory stimulation

When the primary visual cortex (V1) is activated by sensory stimulation, what is the temporal correlation between the synaptic inputs to nearby neurons? This question underlies the origin of correlated activity, the mechanism of how visually evoked activity emerges and propagates in cortical circuits, and the relationship between spontaneous and evoked activity. Here, we have recorded membrane potential from pairs of V1 neurons in anesthetized cats and found that visual stimulation suppressed low-frequency membrane potential synchrony (0-10 Hz), and often increased synchrony at high frequencies (20-80 Hz). The increase in high-frequency synchrony occurred for neurons with similar orientation preferences and for neurons with different orientation preferences and occurred for a wide range of stimulus orientations. Thus, while only a subset of neurons spike in response to visual stimulation, a far larger proportion of the circuit is correlated with spiking activity through subthreshold, high-frequency synchronous activity that crosses functional domains.     

In vivo and in vitro patch-clamp recording analysis of the process of sensory transmission in the spinal cord and sensory cortex

Following the integration and modification of the sensory inputs in the spinal cord, the information is transmitted to the primary sensory cortex where the integrated information is further processed and perceived. Processing of the sensory information in the spinal cord has been intensively investigated. However, the mechanisms of how the inputs are processed in the cortex are still unclear. To know the correlation of the sensory processing in the dorsal horn and cortex, in vivo and in vitro patch-clamp recordings were made from rat dorsal horn and sensory cortex. Although dorsal horn neurons showed spontaneous and evoked EPSCs by noxious and non-noxious stimuli, most somatosensory neurons located at 100 to 1000 microm from the surface of the cortex exhibited an oscillatory activity and received synaptic inputs from non-noxious but not noxious receptors. These observations suggest that the synaptic responses in cortical neurons are processed in a more complex manner; and this may be due to the reciprocal synaptic connection between thalamus and cortex.     

Serotonin (5-HT2) receptor mediated enhancement of cortical unit activity.

Simultaneous single-unit and intracortical activity were recorded from neocortical neurons in urethane-anaesthetized rats to investigate the role of serotonin (5-HT) in modifying cortical excitability. Units, at a depth of 775-1100 microns from the pial surface, discharged in a burst-pause pattern that was correlated with slow wave activity. Application of noxious somatic stimulation resulted in cortical desynchronization and altered the pattern of unit activity such that firing was continuous, i.e., the pauses were eliminated. Intravenous administration of the mixed 5-HT1C/5-HT2 antagonists (cinanserin, cyproheptadine, ketanserin, and ritanserin) prevented both desynchronization and the change in unit activity induced by noxious stimulation within 2.5-15 min of the injection. The basic pattern of burst-pause activity remained intact, but the number of spikes per burst was typically reduced, whereas interburst intervals were increased. Iontophoretic application of these antagonists onto cortical neurons resulted in actions similar to those observed following systemic administration. Intravenous and iontophoretic application of m-trifluomethylphenylpiperazine (5-HT1C agonist, 5-HT2 antagonist) resulted in actions indistinguishable from those observed with the above antagonists, from which we conclude 5-HT2 and not 5-HT1C receptors mediate the alteration in unit activity observed with noxious stimulation. The results are discussed with respect to an interaction between N-methyl-D-aspartate and 5-HT2 receptors leading to the enhanced unit activity observed with noxious stimulation.     

Microiontophoretically applied THIP effects upon nociceptive responses of neurons in medial thalamus

Sprague-Dawley rats anesthetized with urethane were used to study the single cell responses of medial thalamic neurons following noxious input and their interactions with gamma-aminobutyric acid (GABA) agonist THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol) and morphine sulfate applied microintophoretically . The majority of the medial thalamic neurons responded to noxious stimulation by an increase in their firing rate. Local application of both THIP and morphine attenuated the spontaneous and the noxious evoked responses of these neurons. The possibility of a role for GABA in mediating nonopiate pain suppression is discussed.     

The late excitatory responses of the motor cortex neurons in the cat to stimulation of the pyramidal tract

Under conditions of partial suppression of GAMKA-dependent cortical inhibition in the motor cortex of anesthetized cats, a weak electrical stimulation of the pyramidal tract evoked the late slow (50-200 ms) excitatory reactions in the motor cortex neurons similar to those previously recorded under the same conditions in response to stimulation of the parietal cortex. This finding favors the proposal that the late excitatory component of the cortico-cortical response reflects the repetitive activation of cortical neurons due to excitation spread via the system of cortical recurrent excitatory collaterals.     

The morphofunctional characteristics of the neurons in the sensorimotor cortex of old rabbits during the trace assimilation of rhythm]

Extracellular neuronal activity was recorded from 460 neurons from alert young (5-7 months), middle-aged (54-65 months) and old (66-85 months) rabbits. Trace rhythmic activity of sensorimotor cortical neurons was examined after long-lasting (10-20 min) rhythmic (0.5-2 Hz) electrocutaneous stimulation of the contralateral forelimb. Spectral analysis of spike activity showed age-related differences in capability of producing a rhythm of previous stimulation in spontaneous neuronal activity. In young animals propriate rhythmic fluctuations of firing rate appeared after the first or second sessions of stimulations (on the first experimental day), in middle-aged ones--after 2-4 sessions (on the second or third days); cortical neurons in old rabbits did not exhibit trace rhythmic activity. Significant morphological changes in glial and neuronal cells were observed in sensorimotor cortex of old rabbits. It is proposed that morphological deteriorations may be the reason of the impairement of trace processes during aging.     

Comparative study of effect of cortical nucleus of amygdala and pyriform cortex on activity of bulbar respiratory neurons in cats

Comparative microelectrophysiological study of character and peculiarities of effects of the cortical nucleus of amygdala and of the periamygdalar area of pyriform cortex on impulse activity was performed on the same single functionally identified respiratory medullar neurons. A high reactivity of bulbar respiratory neurons to stimulation is established in both studied limbic structures. There is established the qualitatively different character of their response reactions at stimulation of the cortical amygdala nucleus and the periamygdalar cortex. The cortical amygdala nucleus has been shown to produce both facilitating and inhibitory effects (with predominance of the activating one) on activity of medullar respiratory neurons (without topographical orderliness). The effect of periamygdalar cortex at stimulation of various parts was characterized by topographic differentiation. The suppressing reactions of neurons in the majority of cases were recorded at stimulation of the rostral area of periamygdalar cortex, whereas the excitatory reactions-at stimulation of its caudal part. Functional organization of respiratory control of the studied limbic system structures is discussed.     

Spontaneous activity level and spike responses of cortical neurons to local supply of amino acids for dendrites and soma

In guinea-pig parietal cortex slices, it was shown that neuronal spontaneous activity depended on dendro-somatic propagation of excitations evoked in dendrites. The functional dendritic properties are essentially non-uniform in the population of cortical neurons. Spike responses to direct soma activations are quite stable among neurons with various levels of spontaneous activity.     

Spontaneous and evoked unit activity in the visual cortex in mutant mice

Spontaneous and evoked unit activity was investigated in the visual cortex of mice with the "ocular retardation" (or/or) mutation, in which the action of the gene is manifested phenotypically by defective development of the optic nerve, with the consequent total blindness of the animals. Control experiments were carried out on inbred C57Br mice. A raised level of spontaneous activity was found in the neurons of the mutant animals and also differences in the distribution of the cells on the basis of the types of their spontaneous activity: A regular type of activity was found 2.5 times more often in the "or/or" mice than in the control group, whereas the proportion of cells with a volley type of discharge was 2.7 times smaller. In addition, visual cortical neurons of the "or/or" mice were more able to respond to acoustic stimulation, when 78% of the responses were tonic in character. Of the unit responses to electrical stimulation of the skin 70% also were tonic, and most were responses of excitation. In 42% of visual cortical neurons of the mutants convergence of heteromodal afferent influences was observed. The functional features described are evidently phenotypical manifestations of the action of the mutant gene on cortical neurons.P. K. Anokhin Institute of Normal Physiology, Academy of Medical Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 8, No. 6, pp. 568–574, November–December, 1976.     

Hypothalamic control of visual cortical unit activity in rabbits

During the action of an extracellular polarizing current on neurons of the rabbit visual cortex electrical stimulation was applied to various hypothalamic nuclei (preoptic region, anterior hypothalamic region, lateral hypothalamus, mammillary bodies, and posterior hypothalamic nucleus). Hypothalamic stimulation was found to reduce the mean discharge frequency of most visual cortical neurons tested under conditions of anodal polarization, when the initial level of activity is considerably increased, than to a decrease in activity under conditions of cathodal polarization, when the initial level of activity is considerably reduced. The same tendency toward restoration of the initial (spontaneous) level of unit activity after hypothalamic stimulation was discovered when this level was shifted as a result of stimulation by regular flashes. The greatest effect was observed during stimulation of the preoptic region of the hypothalamus. Stimulation of the posterior hypothalamic nucleus was least effective in this respect.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 9, No. 5, pp. 469–476, September–October, 1977.     

Role of Alpha-Adrenoreceptors in Cerebello-Cortical Transmission in the Rat

We studied the role of alpha-adrenoreceptors (AR) in the modulation of evoked neuronal activity in the primary motor cortex (PMC). Neurons receiving afferent inputs from the cerebellum were examined using a microiontophoretic technique. Activation of alpha-AR with octopamine resulted in most units (71%) on the intensification of background firing and in a prominent rise (in a dose-dependent manner) in the responsiveness of PMC neurons to stimulation of the superior cerebellar peduncle (SCP). A selective postsynaptic alpha1 antagonist, prazosin, evoked significant dose-dependent suppression of the background and evoked activity in 84% of the tested neurons. A selective presynaptic alpha2 antagonist, yohimbine, provided diverse effects. Its application exerted an excitatory effect in 50% of the studied neurons; however, in 33% of the cells qualitatively opposite alterations were observed: in low doses yohimbine increased the neuronal activity, but in high doses suppressed it. Our findings demonstrate the essential role of alpha-AR in the modulation of cerebro-cortical transmission and suggest their considerable involvement in motor functions.