Inhibitory and excitatory processes in thalamic motor nuclei neurons in the normal nigrostriatal dopaminergic system and following injury to it produced by N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

Excitatory and inhibitory processes in neurons of the thalamic anteroventral and ventrolateral (VA–VL) motor nuclei were investigated in two sets of experiments on cats anesthetized with Ketalar and immobilized by myorelaxant during the course of stimulation of the red nucleus region and following chronic administration of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 5 mg/kg i.m. over a 5-day period): It was found 48 h after the last MPTP injection that up to 48% neurons belonging to the substantia nigra pars compacta had been destroyed and that dopamine level had declined to 30% of that found in intact animals. In cats injected with MPTP inhibitory processes declined significantly in both duration and efficacy in VA–VL relay and non-relay neurons, while latency of orthodromic excitatory response to red nucleus stimulation declined. It is suggested that attenuation of dopamine-modulated GABA-ergic nigrothalamic influences underlies the low level of inhibition occurring.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Institute of Endocrinology and Metabolism, Ukrainian Ministry of Public Health, Kiev. Institute of Organic Chemistry, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 21, No. 5, pp. 620–629, September–October, 1989.     

Neuronal responses of the reticular and anterior ventral thalamic nuclei to stimulation of the thalamic ventrolateral nucleus and motor cortex

Responses of 137 neurons of the rostral pole of the reticular and anterior ventral thalamic nuclei to electrical stimulation of the ventrolateral nucleus and motor cortex were studied in 17 cats immobilized with D-tubocurarine. The number of neurons responding antidromically to stimulation of the ventrolateral nucleus was 10.5% of all cells tested (latent period of response 0.7–3.0 msec), whereas to stimulation of the motor cortex it was 11.0% (latent period of response 0.4–4.0 msec). Neurons with a dividing axon, one branch of which terminated in the thalamic ventrolateral nuclei, the other in the motor cortex, were found. Orthodromic excitation was observed in 78.9% of neurons tested during stimulation of the ventrolateral nucleus and in 52.5% of neurons during stimulation of the motor cortex. Altogether 55.6% of cells responded to stimulation of the ventrolateral nucleus with a discharge of 3 to 20 action potentials with a frequency of 130–350 Hz. Similar discharges in response to stimulation of the motor cortex were observed in 30.5% of neurons tested. An inhibitory response was recorded in only 6.8% of cells. Convergence of influences from the thalamic ventrolateral nucleus and motor cortex was observed in 55.7% of neurons. The corticofugal influence of the motor cortex on responses arising in these cells to testing stimulation of the ventrolateral nucleus could be either inhibitory or facilitatory.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 10, No. 5, pp. 460–468, September–October, 1978.     

Reactions of cat motor cortex neurons to stimulation of the pyramidal tract and ventroposterolateral thalamic nuclei

Responses of neurons of motor cortex evoked by stimulations of pyramidal tract (PT) and ventroposterolateral (VPL) nucleus of thalamus were studied in cats immobilized by Myorelaxin. Antidromic spikes were found in 22.6% and in 9.9% of cortical cells when PT and VPL were stimulated, respectively. Fast- and slow-conducting PT-neurones could be differentiated according to antidromic excitation latencies. PT stimulation evoked EPSPs in 46.3% of studied neurones and VPL stimulation--in 48.2% ones. Monosynaptic EPSPs were identified in responses of fast- and slow-conducting PT-units and of neurones projecting in VPL; mechanisms and functional role of such reactions are discussed. Di- and polysynaptic IPSPs were evoked in 74.5% of units by PT stimulation and in 94.4%--by VPL stimulation. Three groups of IPSPs were classified with durations to 120, 130-280 and more than 300 ms. Duration of PT-evoked IPSPs was higher in cortical neurones from surface layers and VPL-evoked ones--in units localized in deep layers.     

Role of intralaminar thalamic nuclei in strengthening inhibition induced by stimulation of the caudate nucleus

The influence of preliminary subthreshold activation of thalamic intralaminary nuclei on achievement of instrumental reflex and on inhibitory effects, caused by stimulation of the caudate nucleus head, were studied in chronic experiments on 5 dogs with a model of instrumental defensive conditioned reflexes, providing for maintainance of a given posture. It was shown that the preceding high-frequency electrostimulation of intralaminary nuclei activates motor components of the instrumental response (shortened latency, EMG and mechanogram of the response, increased amplitude of instrumental response) and significantly lowers threshold strength of the current, necessary for obtaining "caudate pause". The greatest increase in inhibitory influences, caused by stimulation of the caudate nucleus head, was observed when thalamic stimulation preceded stimulations, localized in the dorsolateral segment of the caudate nucleus head. The obtained data are discussed in aspect of Buchwald et al. hypothesis on the existence of "caudate loop".     

Unit responses of the cat caudate nucleus to cortical stimulation before and after destruction of nonspecific thalamic nuclei

Responses of caudate neurons to stimulation of the anterior sigmoid and various parts of the suprasylvian gyrus were studied in acute experiments on cats. The experiments consisted of two series: on animals with an intact thalamus and on animals after preliminary destruction of the nonspecific thalamic nuclei. Stimulation of all cortical areas tested in intact animals evoked complex multicomponent responses in caudate neurons with (or without) initial excitation, followed by a phase of inhibition and late activation. The latent periods of the initial responses to stimulation of all parts of the cortex were long and averaged 14.5–25.5 msec. Quantitative and qualitative differences were established in responses of the caudate neurons to stimulation of different parts of the cortex. Considerable convergence of cortical influences on neurons of the caudate nucleus was found. After destruction of the nonspecific thalamic nuclei all components of the complex response of the caudate neurons to cortical stimulation were preserved, and only the time course of late activation was modified.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 12, No. 5, pp. 464–471, September–October, 1980.     

Caudatonigral projections under normal conditions and after an MPTP-induced lesion of the cat nigrostriatal system: Quantitative ultrastructural analysis

Ultrastructural and morphometric studies of caudatonigral synapses located on the nigrothalamic neurons were carried out on intact and N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated adult cats. Three types of synapses with different ultrastructural features were found. Morphometric analysis showed that 11.3% of analyzed junctions were caudatonigral synapses; 5.9% and 5.4% of them were located on the somata of nigrothalamic neurons and on their dendrites respectively. Among axo-somatic synapses, the caudatonigral ones amounted to 11.9%: 7.6% were type-I synapses and 4.3% belonged to type-III synapses. Both types had symmetrical contacts and could be considered inhibitory. Caudatonigral axodendritic synapses amounted to 10.6%: 3.2% were of type I; 4.2%, of type III; and 3.2%, of type II synapses with asymmetric contacts. The labelled type-II synapses were found exclusively on the nigrothalamic dendrites. The ultrastructural changes and the statistically significant decrease in the size of caudate axon terminals following the MPTP treatment took place only in the type I exosomatic synapses. It is suggested that the development of motor disorders in the cat after experimentally induced striatal dopamine insufficiency is due to the decrease in the efficacy of caudatonigral influences, which causes disinhibition of GABA-ergic inhibitory nigrothalamic neurons, and to enhanced influences of the latter on the cells of the motor thalamic nuclei.Neirofiziologiya/Neurophysiology, Vol. 26, No. 2, pp. 150–156, March–April, 1994.     

Unit responses of the ventral posterior and ventral lateral thalamic nuclei to electrical stimulation of the thalamic reticular nucleus

A microelectrode investigation was made of responses of 72 physiologically identified neurons of the ventral posterior (VP) and 116 neurons of the ventral lateral (VL) thalamic nuclei to electrical stimulation of the reticular (R) thalamic nucleus. Mainly those neurons of VP and VL (73.7 and 86.2% respectively) which responded to stimulation of the first motor area and nucleus interpositus of the cerebellum responded to stimulation of R; 19.8% of VL neurons tested responded to stimulation of R by an antidromic action potential with latent period of 0.5–2.0 msec and 46.6% of neurons responded by orthodromic excitation; 23% of orthodromic responses had a latent period of 0.9–3.5 msec and 77% a latent period of 4.0–21.0 msec; 19.8% of VL neurons tested were inhibited. Among IPSPs recorded only one was monosynaptic (1.0 msec) and the rest polysynaptic. It is postulated that both R neurons are excitatory and that the inhibition which develops in VL neurons during stimulation of R are connected mainly with activation of inhibitory interneurons outside the reticular nucleus.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 9, No. 5, pp. 477–485, September–October, 1977.     

Reactions of neurons of the orbitofrontal cortex to stimulation of optic thalamic nuclei

The reactions of 288 neurons of the orbitofrontal cortex (OFC) to stimulation of the posteroventral (VP), ventral anterior (VA), and reticular (R) nuclei, as well as the median center (CM) of the thalamus, were investigated in acute experiments on cats. OFC neurons can be divided into four groups by their reactions to stimulation of thalamic nuclei: 1) those which respond with an increase in the frequency of the discharges to single and serial stimuli with a frequency of up to 20/sec; 2) those which respond doubtfully to single stimuli with a frequency of 4–12/sec; 3) those which respond with inhibition of the background impulses; 4) those which do not respond to stimulation of the nuclei. Stimulation of the thalamic nuclei evoked responses of OFC neurons with a large scatter of the latent period duration. The responses of neurons to stimulation of the VP (mean latent period 19.1±6.1 msec) had the shortest latent period (sometimes less than 3–4 msec). Reactions with a longer latent period developed upon stimulation of the VA (23.8±7.4 msec) and CM (42.8±12.8 msec). The uniqueness of the links of the OFC with the various optic thalamic nuclei is shown in an analysis of the material obtained and possible methods of the activation of the neurons of this region from thalamic structures are discussed.State Medical Institute, Kemerovo. Translated from Neirofiziologiya, Vol. 3, No. 4, pp. 350–358, July–August, 1971.     

Effect of electric stimulation of cortical portions of the limbic system on the activity of neurons of the anterior thalamic nuclei in the rabbit

Effects of electrical stimulation of the subiculum (SB) and posterior limbic cortex (PLC) were studied extracellularly in the anteroventral (AV) and anterodorsal (AD) limbic thalamic nuclei of awake chronic rabbits. Stimulation of SB and PLC evoked in some AV neurones discharges of 1-2 spikes. Gradual potentiation and low frequency of following (up to 10-15 Hz) were characteristic of these responses. Activity of the majority of AV cells was suppressed by stimulation with appearance of inactivation bursts, "neuronal spindles" and modulation on delta-frequencies. Spike responses were evoked by SB and (rarely) by PLC stimulation only in a certain class of AD neurones which tentatively are regarded as relay cells. The neurones with high-frequency, low-amplitude discharges (putative inhibitory interneurones) reacted to stimulation of PLC and to a lesser extent of SB by prolonged series of spikes (150 ms--2s). Stimulation of PLC exerted prolonged influence upon neuronal responses to sensory stimuli.     

Functional and structural modifications in cells of theVA-VL thalamic nuclei under the influence of the neurotoxin MPTP

We analyzed the peculiarities of interaction between the cerebellar and pallidal effects on the same thalamic neuron observed in intact cats and in cats injected with N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), as well as ultrastructural changes, which develop in the motor thalamic neurons affected by this toxin. Responses of 225 neurons of the ventral anterior (VA) and ventral lateral (VL) thalamic nuclei were studied in intact animals, and 218 neurons of these nuclei were recorded in MPTP-treated cats. Nerve cells responding to stimulation of both cerebellar and pallidal inputs constituted 7–8% of all neurons under study; they were mostly localized in the medialVA-VL regions. In the norm, conditioning stimulation of the pallidum was accompanied in 68% of the cases by complete inhibition of neuronal responses to test stimulation of cerebellar fibers (at 1- to 6-msec-long interstimulus intervals). After a 5-day-long course of MPTP injections, conditioning pallidal stimulation-induced inhibition of test responses was observed in a much smaller share of the cases (27%). Such a drop in the efficacy of pallidal inhibitory influences may be related to MPTP-induced structural modifications of the pallido-thalamic synapses. Electron microscopic examination showed that MPTP treatment resulted in the development of ultrastructural manifestations of hydropic dystrophy and clearly expressed depletion of synaptic vesicles in the F1-type synapses distributed on the dendrites of thalamo-corticalVA-VL neurons (these synapses, according to their structural features, were identified as pallido-thalamic contacts). A decrease in the dimension of axon terminals and intensified osmium staining of the synaptoplasm were also observed.     

Unit responses of the thalamic and ventral anterior thalamic nuclei to electrical stimulation of thalamic relay nuclei in cats

Responses of 92 neurons of the reticular (R) and 105 neurons of the ventral anterior (VA) thalamic nuclei to stimulation of the ventrobasal complex (VB) and the lateral (GL) and medial (GM) geniculate bodies were investigated in cats immobilized with D-tobocurarine. Altogether 72.2% of R neurons and 76.2% of VA neurons responded to stimulation of VB whereas only 15.0% of R neurons and 27.1% of VA neurons responded to stimulation of GM and 10.2% of R neurons and 19.6% of VA neurons responded to stimulation of GL. The response of the R and VA neurons to stimulation of the relay nuclei as a rule was expressed as excitation. A primary inhibitory response was observed for only two R and three VA neurons. Two types of excitable neurons were distinguished: The first respond to afferent stimulation by a discharge consisting of 5–15 spikes with a frequency of 250–300/sec; the second respond by single action potentials. Neurons of the first type closely resemble inhibitory interneurons in the character of the response. Antidromic responses were recorded from 2.2% of R neurons and 7.8% of VA neurons during stimulation of the relay nuclei. Among the R and VA neurons there are some which respond to stimulation not only of one, but of two or even three relay nuclei. If stimulation of one relay nucleus is accompanied by a response of a R or VA neuron, preceding stimulation of another nucleus leads to inhibition of the response to the testing stimulus if the interval between conditioning and testing stimuli is less than 30–50 msec.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 8, No. 6, pp. 597–605, November–December, 1976.     

Modulating effect of electric acupuncture stimulation on the bioelectrical activity of neurons of specific and nonspecific thalamic nuclei

Bioelectric reactions of individual neurons in specific and nonspecific thalamus nuclei were studied in acute experiments on cats. Auricular or body point electroacupuncture (EAP) was shown to affect the functions of spontaneously active neurons in the nuclei under study. Two types of spontaneously active neurons were identified: some were activated and some inhibited in response to EAP stimulation. The number of neurons activated in response to EAP was 50% greater in specific thalamus nuclei than in nonspecific ones, while inhibition was mostly observed in nonspecific thalamus cells.     

6-OHDA毁损黑质致密部对大鼠PPN和VL神经元放电活动的影响

目的：观察6-羟多巴胺单侧毁损黑质致密部多巴胺神经元后,脚桥核（PPN）和丘脑腹外侧核（VL）神经元自发放电活动的变化,探讨帕金森病（PD）的发病机制。方法：应用玻璃微电极细胞外记录法,观察对照组和PD组PPN和VL神经元的放电频率和放电形式的变化。结果：对照组和PD组大鼠PPN放电频率分别为（8．31±0．62）Hz和（10．70±0．85）Hz,PD组放电频率明显高于对照组（P〈0．05）。和对照组相比,PD组PPN的不规则和爆发式放电神经元构成比例明显增多（P〈0．01）,同时规则放电频率增加（P〈0．01）。对照组和PD组大鼠VL的放电频率分别为（6．25±0．54）Hz和（5．67±0．46）Hz,两组间没有显著性差异。VL神经元放电形式表现为不规则和爆发式放电,两组间构成比也没有明显差异,但PD组爆发式神经元放电频率明显降低（P〈0．01）。结论：PD状态下,PPN神经元活动增强,PPN可能参与了PD的病理生理过程,VL神经元放电可能受PPN神经元投射的调节。     

Effect of damage of the nigro-neostriatal dopaminergic system by MPTP on the transmission of corticofugal impulses to the neurons of the caudate nucleus

It is shown in acute experiments on cats (males) that the induced responses as action potentials (AP) by the latent period (LP) less than 8.0 ms in the caudate nucleus neurons (CN) to a single stimulation of the motor zone of the cortex (MI) are more frequently inhibited than facilitated after specifying single stimulation of the compact part of the black substance (BS) in the intervals between stimuli 10-100 ms. As a result of system multiple injection of MPTP neurotoxin during 5 days per 5 mg/kg the number of CN neurons responding to stimulation of MI, AP, LP less than 8.0 Usec and to stimulation of BS-LP less than 10.0 ms reliably decreases. A conclusion is made that dopaminergic nigro-striatum system exerts a protective action on the impulse transfer on monosynaptic connections from the cortex to striatum.     

Impulse response of neurons of the thalamic reticular nucleus to extraneous stimulation in conditioned-reflex trained cats

During heteromodal extraneous stimulation (ES), a large part of responding neurons of the thalamic reticular nucleus (RN) exhibit selectivity by responding with excitation to the stimulation of only one type of sensory input. To visual ES, 12 of 32 tested neurons responded; and 4 of 21 tested neurons responded to auditory ES. Response of neurons to ES diminished during the process of habituation to these stimuli; and after habituation was completed, the number of neurons responsive to the ES also diminished. Use of ES led to disappearance of high-frequency, grouped discharges in the responses of the RN neurons. Initial responses to ES and to the following conditioning stimulus (CS) appeared during external inhibition of the conditioned reflex (CR), but the later components of impulse responses that ordinarily accompany realized CR were suppressed in nearly one half of the studied neurons. We reach the conclusion that RN neurons participate in external inhibition of CR and in habituation to ES.A. A. Bogomolets Physiology Institute, Academy of Sciences of the USSR, Kiev. Translated from Neirofiziologiya, Vol. 23, No. 2, pp. 189–199, March–April, 1991.