Effect of stimulation of beta-adrenergic receptors on neuronal activity in primary motor cortex of the rat.

Modulatory influence of beta1- and beta2-subtypes of adrenergic receptors (ARs) on the background neuronal activity and cerebellocortical transmission was characterized in the rat primary motor cortex (M1). Microiontophoretic administration of non-selective beta-ARs agonist isoproterenol significantly decreased firing rate and responses to superior cerebellar peduncle stimulation in 82% of studied neurons in a dose-dependent manner. Similar changes were induced by ejection of selective beta1-ARs agonist dobutamine, while fenoterol (selective beta2-ARs agonist) increased or reduced firing rate in 32% and 19% of M1 neurons, respectively. Non-selective beta-ARs antagonist propranolol enhanced both the background and evoked activity in 84% of tested neurons. These data provided the functional evidence for beta-ARs-mediated inhibition (predominantly through beta1-subtype) of cerebellocortical input to M1. The possible mechanism of the positive therapeutic effect of propranolol in tremor-predominant Parkinson's disease is discussed.

Basal ganglia and processing of cortical information: functional interactions between trans-striatal and trans-subthalamic circuits in the substantia nigra pars reticulata.

The substantia nigra pars reticulata (SNR), a major output station of basal ganglia, receives information from the cerebral cortex through three main pathways, i.e. a direct inhibitory trans-striatal pathway, an indirect excitatory trans-striatal pathway that involves the pallidum and the subthalamus and a direct excitatory trans-subthalamic pathway. In order to determine how cortical information flow originating from functionally distinct cortical areas and processed through the trans-striatal and trans-subthalamic pathways is integrated within the SNR, the responses induced by electrical stimulation of prefrontal, motor and auditory cortex in SNR cells were analyzed in anesthetized rats. Further confirming that direct striato-nigral pathways related to these functionally distinct cortical areas are organized in parallel channels, stimulation of the prefrontal, motor and auditory cortex induced an inhibitory response on distinct subpopulations of SNR cells. Within a given channel, the direct trans-striatal and the trans-subthalamic pathways converge on a large number of nigral cells. In addition, the present study reveals that nigral cells receiving an inhibitory input from a given cortical area through the direct trans-striatal pathway can also receive an excitatory input from a functionally distinct cortical area through the trans-subthalamic pathways. Such a convergence mainly occurred between the direct striato-nigral pathway issued from the auditory cortex and the trans-subthalamic pathways issued from the motor cortex. These data reveal the existence of a converging influence of trans-subthalamic and direct striato-nigral pathways not only within but also across channels. Within a given cortico-basal ganglia channel, the trans-subthalamic pathways likely contribute to the temporal shaping of the striato-nigral inhibition and thus of the disinhibition of the related nigral target nuclei in the thalamus and mesencephalon. Across channels, the specific interactions between trans-subthalamic and direct striato-nigral pathways could contribute to prevent inhibition of subpopulations of nigral cells implicated in competing functions.

Segregation and convergence of information flow through the cortico-subthalamic pathways.

Cortico-basal ganglia circuits are organized in parallel channels. Information flow from functionally distinct cortical areas remains segregated within the striatum and through its direct projections to basal ganglia output structures. Whether such a segregation is maintained in trans-subthalamic circuits is still questioned. The effects of electrical stimulation of prefrontal, motor, and auditory cortex were analyzed in the subthalamic nucleus as well as in the striatum of anesthetized rats. In the striatum, cells (n = 300) presenting an excitatory response to stimulation of these cortical areas were located in distinct striatal territories, and none of the cells responded to two cortical stimulation sites. In the subthalamic nucleus, both prefrontal and motor cortex stimulations induced early and late excitatory responses as a result of activation of the direct cortico-subthalamic pathway and of the indirect cortico-striato-pallido-subthalamic pathway, respectively. Stimulation of the auditory cortex, which does not send direct projection to the subthalamic nucleus, induced only late excitatory responses. Among the subthalamic responding cells (n = 441), a few received both prefrontal and motor cortex (n = 19) or prefrontal and auditory cortex (n = 10) excitatory inputs, whereas a larger number of cells were activated from both motor and auditory cortices (n = 48). The data indicate that the segregation of cortical information flow originating from prefrontal, motor, and auditory cortices that occurred in the striatum is only partly maintained in the subthalamic nucleus. It can be proposed that the existence of specific patterns of convergence of information flow from these functionally distinct cortical areas in the subthalamic nucleus allows interactions between parallel channels.

Influence of the blockade of D2 dopamine receptors of the cat neostriatum on the baseline activity and saccadic eye movement-associated reactions of neurons of the reticular portion of the substantia nigra.

The activity of neurons of the reticular portion of the substantia nigra before and after the microinjection of haloperidol (25 micrograms/5 microliters) into the head of the caudate nucleus on the ipsilateral side was investigated under chronic experimental conditions in cats, using the extracellular microelectrode pickup technique. A significant (p < 0.05) increase, from 34 to 61%, of neurons with the burst type of spontaneous activity was established after the injection of haloperidol. A significant increase in the ratio of the number of excitatory responses to inhibitory responses, from 0.04 to 0.4, was identified among the reactions associated with saccadic eye movements following the microinjection of haloperidol. The number of orienting saccades in response to the visual stimulus decreased against this background from 58 to 37%. The identified changes are regarded as a result of the disinhibition of GABAergic neurons of the reticular portion of the substantia nigra under the influence of the blockade of D2 dopamine receptors of the neostriatum.

[The effect of a blockade of the dopamine D2 receptors in the cat neostriatum on the neuronal background activity and reactions of the reticular portion of the substantia nigra related to saccadic eye movements]. / Vliianie blokady D2 dofaminovykh retseptorov neostriatuma koshki na fonovuiu aktivnost' i reaktsii neironov retikuliarnoi chasti chernoi substantsii, sviazannye s sakkadicheskimi dvizheniia glaz.

In cats, the activity of the substantia nigra reticular part's neurons was extracellularly recorded prior to and after haloperidol administration into the head of the caudate nucleus. The number of neurons with burst-type firing increased after the administration from 34 to 61 per cent. The excitatory/inhibitory responses ratio associated with saccadic eyes movements also increased from 0.04 to 0.4. The above changes seem to follow a disinhibition of the GABA-ergic neurons under the effect of blockade of the neostriatum D2 dopamine receptors.

Participation of nucleus entopeduncularis in motor instrumental reflex and entopeduncular influences on motor thalamic nuclei in normal and MPTP-treated cats.

Activity of entopeduncular neurons was studied in chronic experiments on cats during performance of instrumental movement: pedal pressing and holding. One-hundred and twenty-four neurons were extracellularly investigated in intact animals and 81 neurons in cats treated with N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (5 mg/kg daily, intramuscularly for five days). The mean discharge frequency of nucleus entopeduncularis neurons recorded 48-72 h after the last MPTP injection increased from 12.9 +/- 1.5 to 22.1 +/- 1.4 impulses/s, but dropped to preinjection values within the next ten days. In intact animals and in MPTP-treated cats 23 and 17%, respectively, of neurons changed their activity before or during the movement performance. Along with nucleus entopeduncularis neurons that changed their activity simultaneously with instrumental movement performance, 16% of nucleus entopeduncularis nerve cells in intact cats and 12% in MPTP-treated cats responded 50-800 ms before the myogramme of working forepaw biceps was started. Excitatory responses associated with movement performance in MPTP-exposed cats were more pronounced, indicating enhancement of nucleus entopeduncularis neuronal activity in animals with injured nigrostriatal system. Since nucleus entopeduncularis neurons are inhibitory cells, the increase in their activity had to be accompanied by reinforcement of inhibitory influence on neurons in motor thalamic nuclei. In order to test this hypothesis, two groups of acute experiments were performed on ketamine-anaesthetized and myorelaxine-immobilized cats. Neuronal responses in ventral anterior and ventral lateral thalamic nuclei to nucleus entopeduncularis stimulation were investigated in normal and MPTP-treated animals in doses that were identical to those administered in chronic experiments. In intact cats, 28% of neurons responded to nucleus entopeduncularis stimulation with the latency shorter than 7 ms. In half of the inhibited neurons after the first phase of inhibition lasting 18 +/- 2 ms, the second inhibitory phase was recorded. The duration of the latter was 24 +/- 4 ms. Although in MPTP-treated cats the number of neurons inhibited by nucleus entopeduncularis stimulation was practically the same as in normal ones (24.5%), the first phase tended to be shorter, and a statistically significant increase of the second inhibitory phase duration (up to 50 +/- 11 ms) was found. It was suggested that changes in the inhibitory processes in motor thalamic neurons receiving afferents from nucleus entopeduncularis could be explained by GABAB-mediated hyperpolarization of the neuronal membrane, evoked by increasing pallidothalamic inhibitory influences.

[Electrophysiologic study of influences of the Pulvinar stimulation on the caudate nucleus neurons responding to visual stimulation]. / Electrofiziologicheskoe issledovanie vliianii razdrazheniia Pulvinar na neirony khvostatogo iadra, reagiruiushchie na zritel'nuiu stimuliatsiiu.

Responses of caudate neurons to electrical stimulation of the afferent input from the thalamic nucleus pulvinar 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 ms for units with primary activation and from 20 to 150 ms for inhibited ones, the values are indicative of both rapidly and slowly conducting afferent pathways. A possibility of monosynaptic transmission in the pulvinar-caudate projections is also revealed. Stimulation of pulvinar is found to be efficient for the significant (more than 50%) 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 to pulvinar stimulation is described. The obtained data are discussed in the aspect of the possible role of cortical and subcortical projections of the visual system in the creation of sensory specific responses of the caudate nucleus.

[Effect of nucleus entopeduncularis stimulation on thalamic nuclei motor neurons under normal conditions and after injury of the nigrostriatal dopaminergic system produced by the neurotoxin MPTP]. / Vliianie razdrazheniia éntopedunkuliarnogo iadra na neirony motornykh iader talamusa v norme i na fone porazheniia nigrostriatnoi dofaminergicheskoi sistemy neirotoksinom MFTP.

Two groups of acute experiments were performed on cats anesthetized by ketamine and immobilized by myorelaxine to study reactions of neurons in ventral anterior (VA) and ventral lateral (VL) thalamic nuclei to stimulation of nucleus entopeduncularis (nEp) in normal animals and in those treated with chronic injections of neurotoxin--N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 5 mg/kg, i.m., daily, for five days). It was established that in normal cats 28% of the neurons studied have responded to nEp stimulation by inhibition with the latency shorter than 7 ms. In a half of inhibiting neurons after the first phase of inhibition which lasted 18 +/- 2 ms, the second inhibitory phase was registered. The duration of the latter was 25 +/- 4 ms. In MPTP-treated cats the number of neurons inhibited after nEp stimulation was practically the same as in normal ones (24.5%). A tendency of the first phase shortening and a statistically significant increase of the second inhibition phase duration up to 50 +/- 11 ms were found. It was suggested that changes in the inhibitory processes in VA-VL neurons receiving afferents from nEp might be explained by hyperpolarization of the nerve cell membrane evoked by increasing pallidothalamic inhibitory influences. That hyperpolarization created conditions for a decrease in Cl(-)-dependent and an increase in Ca(2+)-dependent K(+)-related phases of inhibitory postsynaptic potentials.

[Excitation and inhibition processes in the neurons of the thalamic motor nuclei of normal cats and following an N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced lesion of the nigrostriatal dopaminergic system]. / Protsessy vozbuzhdeniia i tormozheniia v neironakh motornykh iader talamusa koshek v norme i posle porazheniia nigrostriatnoi dofaminergicheskoi sistemy, vyzvannogo N-metil-4-fenil-1,2,3,6-tetragidropiridinom.

Peculiarities of excitation and inhibition evoked in motor thalamic nuclei (VA-VL) neurons by electrical stimulation of red nucleus were studied on intact cats and after injection of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 5 mg/kg i.m., p.d. during five days). Two days after the last injection as much as 48% of nigral neurons were destroyed and the content of dopamine in the caudate nucleus fell to 30% as compared to intact animals. Before acute experiments all cats were anaesthetized with ketalar and immobilized with myorelaxine. It was found that MPTP injections caused a decrease of the inhibition duration and effectiveness in relay and nonrelay VA-VL neurons. The inhibition deficiency was accompanied by shortening of latencies of orthodromic responses evoked by red nucleus stimulation and facilitation of antidromic spikes invasion into somata of relay neurons after motor cortex stimulation. It was suggested that the reduction of GABAergic nigro-thalamic influences modulated by dopamine underlay the developing deficiency of inhibition.

[Pathways of visual and auditory information transmission in the caudate nucleus of the cat]. / Puti peredachi zritel'noi i slukhovoi informatsii v khvostatoe iadro koshki.

Visual and auditory projections to the caudate nucleus were studied in cat by combination of the HPR method and experimental degeneration of retinal axons. It was shown that visual information comes to the caudate nucleus not only through the well-known polysynaptic pathways from the cerebral cortex, but also through both oligosynaptic (via pulvinar, lateroposterior nucleus, suprageniculate nucleus and nucleus limitans of the thalamus) and disynaptic pathways (via medial and lateral terminal nuclei of the accessory optic tract, pulvinar, pretectum, intermediate superior colliculus layer, supraoptic nucleus) some of which were found for the first time. Direct retinal inputs to the suprageniculate nucleus were found. Additional sources of auditory information to the caudate nucleus were revealed being as follows: the dorsal nucleus of parvocellular division of the medial geniculate nucleus, deep superior colliculus layer, dorsal and ventral nuclei of the lateral lemniscus. Physiological significance of the revealed pathways for the possible transmission of visual and auditory impulses and a new principle of organization of sensory inputs to the caudate nucleus are discussed.

[Projections of the neurons of the medial terminal nucleus of the accessory optic tract to the caudate nucleus of the cat detected by the combined methods of retrograde axonal transport and experimental degeneration]. / Proektsii neironov medial'nogo terminal'nogo iadra dobavochnogo opticheskogo trakta k khvostatomu iadru u koshki, vyiavliaemye pri sochetanii metodov retrogradnogo aksonnogo transporta i éksperimental'noi degeneratsii.

Projections of neurons of the medial terminal nucleus of the accessory optic tract receiving direct retinal inputs to the head and body of caudate nucleus are shown in cat by the retrograde axonal transport of horseradish peroxidase and experimental degeneration. These projections are mainly ipsilateral and uniformly distributed in the above mentioned parts of the nucleus. The neurons of the medial terminal nucleus establishing synaptic connections with caudate neurons have different shapes and sizes (from 20 X 10 microns to 37.5 X 18 microns) and are located both in the ventral and dorsal parts of the nucleus. Conclusions are made about functional significance of these projections in the regulation of the muscular tension.

[Reactions of neostriatal neurons to direct electric stimulation of the optic tract and to photic stimulation in the alert cat]. / Reaktsii neironov neostriatuma na priamoe élektricheskoe razdrazhenie opticheskogo trakta i na svetovuiu stimuliatsiiu u bodrstvuiushchikh koshek.

Responses of 98 cells in the head and body of caudate nucleus to direct electric stimulation of the optic tract and to visual stimuli were recorded extracellularly in awake chronic cats. 34.6 and 36.2% of the studied cells, respectively, have responded to these types of stimulation. Long-latency (over 40 ms for optic tract and over 80 ms for visual stimulations) excitatory responses prevailed in both cases. Small number of units responded to optic tract stimulation with short (5-14 ms) latencies. Eight of 58 tested cells were activated by both electric and visual stimuli. In this case, responses of the same cells could differ (relatively to the type of applied stimulus) either in pattern or sign. These data are discussed relative to the possible pathways for transfer of the visual information to non-specific brain structures.

[Comparative characteristics of response of neurons of the caudate nucleus to different sensory stimuli in awake cats]. / Sravnitel'naia kharakteristika reaktsii neironov khvostatogo iadra na razlichnye sensornye vozdeistviia u bodrstvuiushchikh koshek.

Extracellular responses of caudate neurons to light slits of various orientations and to clicks have been studied in awake cats. Neurons with specific reaction to particular orientation of the slit could change the response pattern when clicks were applied. The latencies of visual and auditory responses of the same caudate neurons could also differ significantly. Most of such cells were distributed in the body of the caudate nucleus. The possibility of participation of caudate neurons in analysis of visual information is discussed.

[Short-latency responses of neurons of the striate system of the brain to sensory activation]. / Korotkolatentnye otvety neironov striatnoi sistemy mozga koshki na sensornuiu aktivatsiiu.

Experiments were carried out on awake cats to study responses of caudate neurons to different afferent stimuli (visual, auditory, somatic and direct electrical stimulation of medial geniculate body). Mean response latencies varied within 15-55 ms with the maximum value to 200 ms. At the same time 1-10% of cells responded with short latency to all applied stimuli. Significance of short-latency sensory responses in comprehension of principles of sensory processing in non-specific subcortical structures is discussed.

[Participation of the visual projection and association cortical inputs in the formation of responses of neostriatal responses to visual stimuli in the alert cat]. / Uchastie zritel'nogo proektsionnogo i assostsiativnogo kortikal'nykh vkhodov v formirovanii reaksii neironov neostriatuma na zritel'nye razdrazhiteli u bodrstvuiushchikh koshek.

Extracellular responses of caudate neurons to local light stimuli and to electrical stimulation of specific (area 17) and associative (the Clare-Bishop area) cortical zones were studied in awake cats. Stimulation of the Clare-Bishop area was found to be more effective for caudate cell responses in comparison with stimulation of area 17; it influenced more caudate cells (47%), whereas responses to area 17 stimulation occurred only in 8% of investigated cells. The mean latency values also were lower in the first case. Only a few neurons responded to stimulation of the both areas. Responses to visual stimuli and to electrical stimulation of these cortical areas were compared in the same caudate cells. Neurons which responded to visual stimuli were also better activated by the Clare-Bishop stimulation than by stimulation of area 17. Such cells were distributed preferably in the body of caudate nucleus. The possible role of the Clare-Bishop area in transmission of visual information to neostriatum is discussed.

[Divergence of axon collaterals of substantia nigra neurons in the forebrain of the rat: double labeling with fluorochromes and horseradish peroxidase]. / Divergentsiia aksonnykh kollateralei neironov chernoi substantsii v perednem mozge krysy: dvoinoe mechenie fliuorokhromami i peroksidazoi khrena.

The origin of divergent and non-divergent pathways from substantia nigra to the thalamus were studied in experiments on rats using retrograde axonal transport of luminescent tracers and horse-radish peroxidase. Two efferent projection systems are shown: the first--with divergence of axon collaterals to the caudato-putamen of both hemispheres, caudato-putamen and globus pallidus, caudato-putamen and nucleus accumbens, ipsilaterally; the second system is directed to the thalamus, and does not form axon collaterals to striatal structures.