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.     

The role of the basal ganglia in the reproducibility of instrumental reactions acquired to electrostimulation of the hippocampus

In dogs with electrodes implanted into the brain, a defensive instrumental conditioned reflex (CR) was elaborated to light flashes, stimulation of the dorsal hippocampus (DH) and caudate nucleus (CN) stimulation. Reproducibility of the learned movement was tested for the contralateral DN, CN, nucleus accumbens (AN) and pallid globe (PG). In the second series the percent of the elicited movements was compared to EPs, appearing in response to signal and testing stimulation. The degree was elucidated of structures participation in motivational, signal and executive links of CR. Low degree of AN participation in the executive CR link (2-nd series) and a high degree of AN and PG participation in the signal link (3-d series) were shown. Thus, intrasystemic CR generalization was more effective than the intersystemic one.     

Involvement of visual specific and association cortex input in the shaping of neostriatal neuron response to visual stimulation in unanesthetized cats

During chronic experiments on unanesthetized cats neuronal response in the caudate nucleus to the presentation of local photic stimuli and electrical stimulation of the specific (field 17) and the association (Clare-Bishop) areas were compared. Stimulation of the Clare-Bishop area proved more effective than stimulating field 17 for neurons of the caudate nucleus; a response was produced in 47% of test neurons in comparison with 8% of units only in the specific area. Lower average values were observed for latency of neuronal response to stimulation of the Clare-Bishop area. An insignificant number of caudate nucleus neurons were activated as a result of stimulation of both cortical areas. A comparison between the response of one set of neurons to electrical cortical and visual stimulation showed that cells responding to visual stimulation were more highly activated by stimulating the Clare-Bishop area than by stimulation of field 17. This type of neuron predominated in the caudate nucleus. A discussion follows of the possible involvement of the Clare-Bishop area in shaping neuronal response to visual stimulation.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 17, No. 5, pp. 619–627, September–October, 1985.     

Dopamine D-2 receptor-mediated excitation of caudate nucleus neurons from the substantia nigra

Microiontophoretic studies using cats anesthetized with alpha-chloralose were performed to elucidate whether the excitatory response of caudate nucleus (CN) neurons upon stimulation of the pars compacta of the substantia nigra (SN) is mediated by the dopamine D-1 or D-2 receptor. There were rare convergent inputs from the SN and motor cortex (MC) in the CN neurons. Iontophoretic application of haloperidol and domperidone (dopamine D-2 receptor antagonist) produced dose-dependent inhibition of spikes elicited by SN stimulation in 25 of 42 and 50 of 82 CN neurons, respectively, however, no alterations of spikes elicited by MC stimulation occurred in any 11 neurons tested. Iontophoretically applied SCH 23390 (D-1 antagonist) did not inhibit the SN-induced spikes in any CN neurons, of which spikes were inhibited by domperidone. These results suggest that the SN-induced spikes are mediated by dopamine, which acts on postsynaptic D-2 receptors.     

Electrophysiological investigation of effect of pulvinar stimulation of caudate nucleus neurons that react to visual stimulation

Responses of caudate neurons to electrical stimulation of the afferent input from thepulvinar thalamic nucleus and to visual stimuli of various orientations were studied extracellularly in awake chronic cats. Activation responses dominated among reactions of these neurons. The response latencies have ranged from 4 to 85 msec for units with primary activation and from 20 to 150 msec for inhibited ones. The values are indicative of both rapidly and slowly conducting afferent pathways. A possibility of monosynaptic transmission in thepulvinarcaudate projections is also revealed.Pulvinar stimulation is found to be efficient for a significant (more than 50 percent) number of caudate neurons responding to visual stimuli, including orientation-selective cells. The mode of influences from other structures of the visual system (optic tract, area 17, the Clare-Bishop area) on caudate neurons responding topulvinar stimulation is described. The data are discussed with respect to the possible role of cortical and subcortical projections of the visual system in the creation of sensory specific responses of the caudate nucleus.A. A. Bogomolets Physiology Institute, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 23, No. 5, pp. 520–529, September–October, 1991.     

Electrophysiological study of corticocaudate projections in cats.

The potential waves evoked in the caudate nucleus (CN) of cats by stimulation of the cerebral neocortex were sterotactically recorded. The head and the body of the caudate nucleus were systematically explored. Stimulation of the ipsilateral sigmoid gyrus and the orbitofrontal cortex evoked waves with the largest amplitude in the CN. Smaller potentials were evoked from the ipsilateral ectosylvian and suprasylvian gyri and from the sigmoid gyrus on the contralateral side. Antidromic conduction from the caudate nucleus to the cortex demonstrated the directness of the corticocaudate pathway. By stimulating the white matter and by amking lesions, the corticocaudate pathway was shown to pass, in part, through the subcallosal fasciculus and, in part, through the internal capsule. Corticocaudate connections were shown to be separate from the fibers of the corticospinal tract. A staggered and extensively overlapping topographic progression of the corticocaudate projections was demonstrable along the antero-posterior axis, but was less evident in the medio-lateral direction. It was concluded that the intranuclear distribution of functional synaptic connections must be more profusely branched than was suspected from anatomical data.     

Electrophysiological study of corticocaudate projections in cats

The potential waves evoked in the caudate nucleus (CN) of cats by stimulation of the cerebral neocortex were stereotactically recorded. The head and the body of the caudate nucleus were systematically explored. Stimulation of the ipsilateral sigmoid gyrus and the orbitofrontal cortex evoked waves with the largest amplitude in the CN. Smaller potentials were evoked from the ipsilateral ectosylvian and suprasylvian gyri and from the sigmoid gyrus on the contralateral side. Antidromic conduction from the caudate nucleus to the cortex demonstrated the directness of the corticocaudate pathway. By stimulating the white matter and by making lesions, the corticocaudate pathway was shown to pass, in part, through the subcallosal fasciculus and, in part, through the internal capsule. Corticocaudate connections were shown to be separate from the fibers of the corticospinal tract. A staggered and extensively overlapping topographic progression of the corticocaudate projections was demonstrable along the antero-posterior axis, but was less evident in the medio-lateral direction. It was concluded that the intranuclear distribution of functional synaptic connections must be more profusely branched than was suspected from anatomical data.     

Responses of caudate neurons to clicks in chronic experiments on cats

Spontaneous and evoked unit activity in response to repeated application of clicks at a frequency of 0.3–2.0 Hz in the caudate nucleus was studied by an extracellular recording technique in chronic experiments on cats. Four types of spontaneous unit activity in the caudate nucleus were distinguished. Altogether 44% of neurons tested responded by changes in spontaneous activity to clicks. Five types of responses of caudate neurons to clicks were discovered: phasic excitation, phasic inhibition, tonic activation, tonic inhibition, and mixed tonic responses; the commonest type was tonic activation. During prolonged stimulation by clicks extinction of the phasic responses was not observed. Complete or partial extinction of tonic responses in the course of frequent repetition of stimulation was observed in 33% of responding neurons. The question of possible convergence of specific and nonspecific influences on caudate neurons is discussed.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 12, No. 1, pp. 28–35, January–February, 1980.     

Excitation by dopamine D-2 receptor agonists, bromocriptine and LY 171555, in caudate nucleus neurons activated by nigral stimulation

Electrophysiological studies using cats anesthetized with alpha-chloralose were carried out to determine whether or not the dopamine D-2 receptor mediates the excitation of the caudate nucleus (CN) neurons activated by stimulation of the substantia nigra (SN). Microiontophoretic application of domperidone (D-2 antagonist) produced a significant inhibition of spikes elicited by SN stimulation in 20 of 27 CN neurons. When bromocriptine and LY 171555 (D-2 agonists) were iontophoretically applied to the CN neurons in which the SN-induced spikes were inhibited by domperidone, an increase in spontaneous firing rate was observed in 18 of 20 neurons and all of 10 neurons tested, respectively. However, no alterations of firing occurred with bromocriptine or LY 171555 in any 7 neurons in which the SN-induced spikes were not affected by domperidone. The increase in firing rate by the D-2 agonists was apparently antagonized during simultaneous application of domperidone and haloperidol, but not affected during application of SCH 23390 (D-1 antagonist). These results strongly suggest that the spike generation of the CN neurons upon SN stimulation is mediated by the dopamine D-2 receptor.     

Corticofugal modulation of initial neural processing of sound information from the ipsilateral ear in the mouse

Background

Cortical neurons implement a high frequency-specific modulation of subcortical nuclei that includes the cochlear nucleus. Anatomical studies show that corticofugal fibers terminating in the auditory thalamus and midbrain are mostly ipsilateral. Differently, corticofugal fibers terminating in the cochlear nucleus are bilateral, which fits to the needs of binaural hearing that improves hearing quality. This leads to our hypothesis that corticofugal modulation of initial neural processing of sound information from the contralateral and ipsilateral ears could be equivalent or coordinated at the first sound processing level.

Methodology/Principal Findings

With the focal electrical stimulation of the auditory cortex and single unit recording, this study examined corticofugal modulation of the ipsilateral cochlear nucleus. The same methods and procedures as described in our previous study of corticofugal modulation of contralateral cochlear nucleus were employed simply for comparison. We found that focal electrical stimulation of cortical neurons induced substantial changes in the response magnitude, response latency and receptive field of ipsilateral cochlear nucleus neurons. Cortical stimulation facilitated auditory response and shortened the response latency of physiologically matched neurons whereas it inhibited auditory response and lengthened the response latency of unmatched neurons. Finally, cortical stimulation shifted the best frequencies of cochlear neurons towards those of stimulated cortical neurons.

Conclusion

Our data suggest that cortical neurons enable a high frequency-specific remodelling of sound information processing in the ipsilateral cochlear nucleus in the same manner as that in the contralateral cochlear nucleus.     

Presynaptic inhibition of excitatory input from the substantia nigra to caudate nucleus neurons by a substituted quinolinone derivative, 7-[3-(4-(2,3-dimethylphenyl)piperazinyl)propoxy]-2(1H)-quinolinone (OPC-4392)

The effects of a newly synthesized quinolinone derivative, 7-[3-(4-(2,3-dimethylphenyl)piperazinyl) propoxy]-2(1H)-quinolinone (OPC-4392) on neuronal activities of the caudate nucleus (CN) were investigated in cats anesthetized with alpha-chloralose using a microiontophoretic method. In the CN neurons of which spikes elicited by stimulation of the pars compacta of substantia nigra (SN) were suppressed by iontophoretically applied domperidone, a dopamine D-2 receptor antagonist, application of OPC-4392 (100-200 nA) inhibited the spike generation induced by SN stimulation. Conversely, the CN neurons insensitive to domperidone were unaffected by OPC-4392. Iontophoretic application of CPC-4392 up to 200 nA did not affect glutamate-induced firing of the CN neurons, of which the firing was blocked by dopamine less than 100 nA. In addition, OPC-4392 did not inhibit firing induced by bromocriptine, a dopamine D-2 agonist; while domperidone suppressed the bromocriptine-induced firing without affecting the glutamate-induced firing. These results suggest that OPC-4392 acts on the dopaminergic nerve terminals and inhibits excitatory transmission from the SN to the CN.     

Binaural and frequency representation in the primary auditory cortex of the big brown bat, Eptesicus fuscus

This study examines the binaural and frequency representation in the primary auditory cortex (AC) of the big brown bat, Eptesicus fuscus, by using an ear-phone stimulation system. All 306 cortical neurons studied were excited by contralateral sound stimulation but they were either excited, inhibited or not affected by ipsilateral sound stimulation. These cortical neurons were columnarly organized according to their binaural and frequency-tuning properties. The excitation-excitation columns which occupy about 15% of the AC are mainly aggregated within an oval-shaped area of the central AC. The excitation-inhibition neurons and binaural neurons with mixed properties are distributed in the remaining 85% of the surrounding primary AC. Although the best frequency (BF) of these neurons shows a tendency to decrease from high to low along the anteroposterior axis of the primary AC, systematic variation in BF is not always consistent across the entire mapping area. In particular, BFs of cortical neurons isolated in the anterior AC vary quite unsystematically such that neurons with similar BFs are aggregated in isolated patches. Isofrequency and binaural columns are segregated into bands that intersect each other. Accepted: 13 August 1997     

Interaction of influences from the auditory and somatosensory afferent systems on neurons of the primary auditory cortex

In experiments on anesthetized cats, 80 neurons of the primary auditory cortex (A1) were studied. Within the examined neuronal population, 66 cells (or 82.5%) were monosensory units, i.e., they responded only to acoustic stimulations (sound clicks and tones); 8 (10.1%) neurons responded to acoustic stimulation and electrocutaneous stimulation (ECS); the rest of the units (7.4%) were either trisensory (responded also to visual stimulation) or responded only to non-acoustic stimulations. In the A1 area, neurons responding to ECS with rather short latencies (15.6–17.0 msec) were found. ECS usually suppressed the impulse neuronal responses evoked by sound clicks. It is concluded that somatosensory afferent signals cause predominantly an inhibitory effect on transmission of an acoustic afferent volley to the auditory cortex at a subcortical level; however, rare cases of excitatory convergence of acoustic and somatosensory inputs toA1 neurons were observed.     

Responses of caudate neurons to various visual stimuli in alert cats

Responses of caudate neurons to two kinds of visual stimuli, namely diffuse light and a more local stimulus (a slit of light), oriented in different directions on a screen, were studied in alert cats during natural fixation of the gaze. The number of neurons which responded to local stimulation was several times greater than the number responding to diffuse light. Besides on-responses to local stimulation, a more distinct phase of inhibition of activity during presentation of the stimulus and off-responses also appeared. The latent periods of responses to both kinds of stimulation were commensurate at 40–90 msec for most neurons. Differences in neuronal responses also were found on a change in orientation of the slit. The results are discussed from the standpoint of participation of the caudate nucleus in visual information analysis.     

The effect of electrostimulation of the caudate nucleus and somatosensory cortex on defensive instrumental reactions in dogs]

It has been shown that the effect of stimulation of the caudate nucleus head in the contralateral hemisphere differs at different stages of achievement of a defensive instrumental habit in dogs. Stimulation preceding the action of the conditioned signal or delivered simultaneously with the beginning of the latter did not change the criteria for the achievement of successive programs of the instrumental defensive reaction. Stimulation of the same areas in the last phase of the instrumental response, as a rule, lead to the cessation of instrumental movement. A conclusion has been drawn that in a defensive situation the inhibitory influence of the caudate nucleus on instrumental behaviour of intact dogs is not so sharply expressed as in experiments with alimentary reinforcement. In dogs with a preliminary ablation of the CI and CII cortical zones of the contralateral hemisphere, stimulation of the caudate nucleus head was attended with a sharp drop in every criterion of the instrumental defensive reactions.     

Role of the caudate nucleus in differentiating spatially separated acoustic signals in the dog

In tests on dogs the influence has been studied of bilateral electrolytic lesion of the caudate nuclei heads on realization of acquired conditioned instrumental defensive reactions to spatially separated sound signals (clicks series) under dichotic stimulation. It is shown that caudatectomy does not influence the dogs differentiation of the side of monaural sound stimulation, but leads to their absolute disability for a long time to differentiate right- and left-side positions of the sound image, modelled by changes in interaural difference in time of sound signal arrival at binaural stimulation.     

Coexistence of inhibitory dopamine D-1 and excitatory D-2 receptors on the same caudate nucleus neurons

Microiontophoretic studies using cats anesthetized with alpha-chloralose were performed to determine whether or not dopamine D-1 and D-2 receptors co-exist in the same caudate nucleus (CN) neurons that receive inputs from the substantia nigra (SN), and in which spikes elicited by SN stimulation were blocked by domperidone, a selective D-2 antagonist. Iontophoretic application of dopamine produced a dose-dependent inhibition of spontaneous firing in 2 of 4 spontaneously active CN neurons and an increase in firing in the remaining 2 neurons. However, dopamine inhibited the glutamate-induced firing in 31 of 32 CN neurons that were not spontaneously active. Similar inhibition with iontophoretically applied SKF 38393, a selective D-1 agonist, was observed in 33 of 34 spontaneously inactive neurons tested. When the effects of dopamine, SKF 38393 and bromocriptine (D-2 agonist) were examined on the same CN neurons, the inhibitory effects of both dopamine and SKF 38393 were seen in 14 of 15 neurons, and both an inhibition by SKF 38393 and an excitation by bromocriptine were observed in 15 of 17 neurons. The inhibitory effects of dopamine and SKF 38393 were antagonized by haloperidol and SCH 23390 (D-1 antagonist) without being affected by domperidone. Furthermore, the dopamine-induced inhibition was converted to an excitation during simultaneous application of SCH 23390 in 6 of 10 CN neurons, and this excitation was antagonized by domperidone. These results strongly suggest that the inhibitory D-1 and excitatory D-2 receptors co-exist on the same CN neurons receiving inputs from the SN.     

大鼠初级听皮层神经元对声音空间信息的编码

尽管大脑听皮层神经元对声音空间信息的编码已有不少的研究报道,但其编码机制并不十分清楚,相关研究在大鼠的初级听皮层也未见详细的研究报道．用神经电生理学方法在大鼠初级听皮层考察了151个听神经元的听空间反应域,分析了神经元对来自不同空间方位声刺激反应的放电数和平均首次发放潜伏期的关系．结果表明,多数(52.32%)神经元对来自对侧听空间的声刺激反应较强,表现为对侧偏好型特征,其他神经元分别归类为同侧偏好型(18.54%)、中间偏好型(18.54%)、全向型(3.31%)和复杂型(7.28%)．多数神经元偏好的听空间区域的几何中心位于记录部位对侧听空间的中部和上部．绝大多数初级听皮层神经元对来自偏好听空间的声刺激反应的放电数较多、反应潜伏期较短,对来自非偏好听空间的声刺激反应的放电数较少、反应潜伏期较长,放电数与平均首次发放潜伏期呈显著负相关．在对声音空间信息的编码中,大脑初级听皮层可能综合放电数和潜伏期的信息以实现对声源方位的编码．     

Response of caudate nucleus neurons to a photic stimulus at various locations on the visual field in the awake cat

The response of caudate nucleus neurons to presentation of photic stimuli located at varying distances from the fovea centralis was investigated in awake cats. Stimulation of different sites on the visual field below the fovea produced dissimilar reactions in 25 of the 35 (or 71%) of these neurons responding to photic stimulation. This divergence of response indicates that in 6 of these cells (or 17%) the receptive fields in the test area of the visual field bordered on the central area of the latter and 6 neurons (17%) showed reduced sensitivity to the effects of stimuli nearer to the periphery than to the center of the visual field, while 13 units (37%) were receiving qualitatively different information from various sites on the field of vision. On the basis of our findings we deduced that caudate nucleus neurons are involved in the analysis of visual sensory signals.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 18, No. 2, pp. 241–250, March–April, 1986.     

Responses of neurons of reticular and ventral anterior nuclei of the cat thalamus to afferent stimuli of different modalities

Responses of 146 spontaneously active neurons of the reticular nucleus (R) and of 98 neurons of the ventral anterior (VA) nucleus of the thalamus to electrical stimulation of the skin of the footpads, to flashes, and to clicks were studied in experiments on cats immobilized with D-tubocurarine or myorelaxin. Stimulation of the contralateral forelimb was the most effective: 24.9% of R neurons and 31.3% of VA neurons responded to this stimulation. A response to clicks was observed in only 4.4% of R neurons and 2.4% of VA neurons. Nearly all responding neurons did so by phasic (one spike or a group of spikes) or tonic excitation. Depression of spontaneous activity was observed only in response to electrical stimulation of the skin. Depending on the site of stimulation, it was observed in 2.6–4.3% of R neurons and 1.7–2.1% of VA neurons tested. The latent period of the phasic responses of most neurons was 6–64 msec to electrical stimulation of the contralateral forelimb, 11–43 msec in response to stimulation of the hindlimb on the same side, 10–60 msec to photic and 8–60 msec to acoustic stimulation. Depending on the character of stimulation, 75.1–95.6% of R neurons and 68.7–97.6% of VA cells did not respond at all to the stimuli used. Of the total number of cells tested against the whole range of stimuli, 25% of R neurons and 47% of VA neurons responded to stimulation of different limbs, whereas 16% of R neurons and 22% of VA cells responded to stimuli of different sensory modalities. The functional role of the convergence revealed in these experiments is to inhibit (or, less frequently, to facilitate) the response of a neuron to a testing stimulus during the 40–70 msec after conditioning stimulation.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 7, No. 6, pp. 563–571, November–December, 1975.