Morpho-functional effects of kainic acid injection into the cat's pulvinar-lateralis posterior nucleus complex

The histological, electroencephalographic, behavioral changes as well as the changes in the intensity threshold of stimulation necessary to induce contralateral turning were studied in 16 cats, in which kainic acid (KA) was injected locally into the pulvinar-lateralis posterior nucleus complex (P-LP). In 13 cats a stainless-steel tube with two attached electrodes was implanted in P-LP, and electrodes were also implanted in the ipsilateral dorsal hippocampus, the superior colliculus and the caudate nucleus. KA was injected through the tube using a 10 microliters Hamilton syringe. In other 3 cats, KA was injected stereotaxically through the needle of the Hamilton syringe and two electrodes were implanted in these areas after withdrawal of the syringe. The intensity thresholds of stimulation required to induce turning behavior were controlled before and after KA administration in the 13 cats with an implanted tube and only after KA injections in the three cats without a tube; in these instances the current threshold of the contralateral P-LP served as control. The histological results showed a moderate KA damage of the P-LP, with destruction of neuronal soma and gliosis and additional involvement, in all the experiments, of the dorsal hippocampus; however, passage fibers were spared by the lesions. A dose-dependent epileptic effect of KA was seen, which was slight with the 3 micrograms dose and intense with 6 micrograms. The EEG recording showed a prominent and almost simultaneous epileptic involvement of the hippocampus and the P-LP after KA, with less involvement of the other implanted structures. Turning behavior induced by electrical stimulation of the P-LP was suppressed when the electrode tip was located inside the lesioned area. When the electrode tip was placed inside a slight or moderate damaged tissue, a significative increase in current threshold was found, and finally when the tip of the electrode was outside the lesioned area no change in threshold was observed. These findings do not contradict our previous hypothesis of an intrinsic cholinergic mechanism involved in the turning response evoked by P-LP electrical stimulation, although it cannot be excluded that fibers coming presumably from the superior colliculus or pretectum may contribute to the response.     

The head-eye-body turning behavior induced by electrical or cholinergic stimulation of the pulvinar-lateralis posterior nucleus complex is not dependent on the catecholaminergic system

Two experimental designs were developed in cats in order to analyze the role of the catecholaminergic system in the turning response evoked by cholinergic or electrical stimulation of the pulvinar-lateralis posterior nucleus complex (P-LP). Twenty one adult cats were employed. In one series of experiments, nine cats had a cannula implanted in one P-LP, and through it, apomorphine alone or mixed with carbachol were microinjected. The behavior was observed and the EEG was recorded. In the second experimental design, a cannula and bipolar electrodes were implanted unilaterally in the P-LP of nine cats, and a series of electrical stimulations were performed before and after 6-OHDA administration into the P-LP, and apomorphine was injected parenterally in order to induce turning behavior. Finally three cats received 16 micrograms of 6 OHDA into the P-LP, through a Hamilton syringe and no electrodes or cannula were implanted, to study the histological damage. No evidence of involvement of the catecholaminergic system was found in either of these two experimental series. These results contrast with what has been found in the nigrostriatal dopaminergic system, where an imbalance in dopamine concentration induces turning behavior. High doses (16 micrograms) of 6-OHDA induced minimal damage in the P-LP.     

Role of the pulvinar-lateralis posterior nucleus complex (P-LP) in the experimental epilepsy of the cat

The ability of the pulvinar-lateralis posterior nucleus complex (P-LP) to evoke epileptic activity when stimulated, was studied in 20 adult cats. Twelve animals were analyzed after they recovered from the surgical procedure (chronic model). In seven of them a cannula with electrodes was implanted in the P-LP and one twisted bipolar electrode was placed ipsilaterally in the following structures: hippocampus, superior colliculus, caudate nucleus and cerebral cortex. Through the cannula Na penicillin was injected. The electrodes allowed both to stimulate and to record the electrical activity. In the remaining five cats, the cannula was implanted in hippocampus in order to compare its sensitivity to generate epileptic activity to that of P-LP. Another group of eight cats were surgically implanted and studied in the same day (acute model). In four of them the cannula was placed in the P-LP through the temporal pathway, to avoid crossing the hippocampus and the ventricle. In another four, penicillin was injected in the P-LP after suctioning the cerebral cortex and the hippocampus overlying the former structure. Epileptic activity could be induced in P-LP and it spread rapidly to hippocampus and after a while to the other implanted structures. This was observed both with penicillin and electrical stimulation. The sensitivity of P-LP to generate epileptic activity was lower than that of the hippocampus. In particular, it was necessary to use two to ten times more penicillin and three times the electrical current intensity in the P-LP as compared to the values needed in the hippocampus. These results are discussed in view of the controversial problem about the ability of the thalamus to generate and spread epileptic activity.     

Afferent connections of the nuclei of dorsal columns of spinal cord

The authors studied structural origins of the conduction of the dorsal chord afferent projections to contralateral dorsal column nucleus in cats, which were discovered after foreleg electrical stimulation by the evoked responses method. This evoked responses remain after unilateral section of the medial lemniscus. It was shown the existence of not classical connections which cross to another side at the level of spinal cord and caudal division of brain stem. The discovery fibres contact with other projection systems and form all known types of interneuronal contacts.     

Effect of adrenalin and adrenal desympathization on brain-seizure activity

The effect of adrenalin and bilateral adrenal desympathization on brain-seizure activity evoked by electrical stimulation of the dorsal hippocampus was studied in adult cats. A few days after bilateral adrenal desympathization the threshold of epileptogenic hippocampal stimulation was lowered and the duration of the evoked seizure response increased. Intravenously injected adrenalin raised the threshold of epileptogenic hippocampal stimulation. After injection of small doses of adrenalin directly into the mesencephalic reticular formation the evoked seizure activity was inhibited: The threshold of epileptogenic hippocampal stimulation was raised and the total duration of the seizure discharges reduced. It is postulated that one of the important factors limiting brain-seizure activity is an increase in the circulating blood adrenalin level.     

Hypothalamo — Hyppocampal interrelationships

Changes in hippocampal electrical activity in response to electrical and chemical stimulation of different parts of the hypothalamus were studied in cats with permanently implanted metallic electrodes and a chemical electrode. The results showed that: 1) in response to electrical stimulation of the middle part of the lateral hypothalamus, evoking activation of feeding behavior, the hippocampal theta-rhythm is increased and the delta- and alpha-rhythms are simultaneously depressed; 2) the same picture is observed in response to electrical stimulation of other parts of the lateral hypothalamus, evoking a response of alertness, anxiety, and aggression; 3) after injection of 0.007 ml noradrenalin into the lateral hypothalamus of cats the animals develop a food response, and injection of 0.014 ml acetylcholine causes activation of drinking behavior; these responses take place in association with intensification of the hippocampal theta-rhythm; electrical stimulation of the dorsomedial nucleus evokes desynchronization of hyppocampal electrical activity; 5) in response to threshold stimulation of the ventromedial nucleus, feeding behavior is inhibited and this is accompanied by desynchronization of hyppocampal electrical activity, whereas in response to stronger stimulation, a response of aggression develops and the theta-rhythm is intensified.Institute of Physiology, Academy of Sciences of the Georgian SSR, Tbilisi. Translated from Neirofiziologiya, Vol. 2, No. 5, pp. 497–506, September–October, 1970.     

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.     

Effects of cortical ablations on the turning response evoked by stimulation of the pulvinar-lateralis posterior nucleus complex in the cat

The role played by the cerebral cortex on turning responses elicited by electrical stimulation of P-LP was studied in 9 chronic cats. In three animals the sensorimotor cortex was bilaterally ablated and the threshold values for inducing a turning response were determined. None of the cats showed abnormal threshold values. In six cats the cerebral cortical area known to have reciprocal anatomical connections with P-LP was unilaterally removed. Seven days after surgery, 50% of the electrodes gave no responses; 25% evoked responses with high thresholds and 25% with normal thresholds. One month after surgery the percentages were: 14, 18 and 68 respectively. Histological findings show important fiber and neuronal degeneration in P-LP. It is postulated that this area of the cerebral cortex plays, a facilitatory role on the P-LP ability to induce turning response and that the recovery of this ability can be explained by the development of P-LP denervation supersensitivity.     

Role of the hippocampus and its monoamine reactive systems in the sleep mechanisms of the cat

In adult male cats with chronically implanted electrodes and canules, serotonin (5-OT) microapplication in doses of 15-30 mkg bilaterally in the dorsal hippocampus, elicited a change of temporal characteristics of slow-wave (SWS) and paradoxical (PS) sleep and intensified phasic reactions. At doses of 30 mkg, 5-OT in the SWS stage produced periods of somnambulistic forms of behaviour, turning sometimes in real awakening. Microapplication of noradrenaline (NA) in the dorsal hippocampus in doses of 15-30 mkg elicited changes of temporal characteristics of SWS and PS and inhibited phasic reactions. Large doses (30 mkg) of NA, in PS phase elicited fragments of SWS. In the PS stage 5-OT caused dominance of 6.5 Hz frequency of the theta-rhythm of the hippocampus, NA in small doses (15 mkg) in the PS phase led to theta-rhythm dominance at the 4-5 Hz frequency. It is suggested that the hippocampus and its monoaminoreactive systems participate in central mechanisms of PS phasic type.     

The effect of electric stimulation of different regions of the cerebral cortex on the alimentary reaction in rabbits]

The influences of different parts of the neocortex on the rabbit alimentary behaviour produced by stimulation of the hypothalamic "alimentary centre" were studied in chronic experiments on rabbits with electrodes implanted in different formations of the limbic system and the midbrain. It has been found that electrical stimulation of the frontal and anterior parietal cortical areas raised the threshold of the evoked alimentary reaction. Inhibitory influences of the frontal areas proved to be stronger and more prolonged than those of the anterior parietal area. Electrical stimulation of the posterior parietal and occipital cortical areas decreased the threshold of the evoked alimentary reaction. Coagulation of the dorsal hippocampus eliminated the inhibitory influences of the neocortex, while coagulation of the mesencephalic reticular formation discontinued the facilitating influences of the neocortex on the alimentary reaction.     

Changes in seizure activity thresholds of the cat brain in various stages of sleep and wakefulness

Changes in seizure activity of the brain evoked by electrical stimulation of the dorsal hippocampus in various stages of sleep and wakefulness were studied in adult cats. During slow sleep, when the EEG is dominated by high-voltage slow waves, near-threshold epileptogenic hippocampal stimulation evokes well-marked paroxysmal discharges. During wakefulness or the paradoxical phase of sleep, when the EEG is desynchronized, this hippocampal stimulation is less effective: either no seizure discharges are produced or they are weak. Activation of the mesencephalic reticular formation before epileptogenic hippocampal stimulation hinders the appearance of seizure activity whereas activation after hippocampal stimulation does not inhibit paroxysmal discharges already in progress; on the contrary, in some cases they are actually strengthened a little. One of the main factors limiting the appearance and spread of seizure activity is considered to be the tonic inhibitory influence of the neocortex on other parts of the brain.     

Generalization of an instrumental defensive conditioned reflex elaborated to electric stimulation of the hypothalamus in dogs

Generalization of defensive conditioned reflexes elaborated to electrical stimulation of the lateral hypothalamus (LH) was studied in four dogs with electrodes implanted in various structures of the limbic system. Electrocutaneous stimulation was switched off when the dog lifted the foreleg to a definite level. Generalization of the conditioned reflex was manifested in different degrees when testing different formations of the limbic system, or testing one and the same structure, but at different stages of conditioning. Two types of generalization were found: the first one--a well pronounced motor reaction, by its latency, level and duration of lifting the foreleg similar to movements appearing in response to the conditioned stimulus; and the second one--low amplitude or short-term movements differing from conditioned ones. The first type of generalization was observed in response to stimulation of LH, contralateral to the point of signal stimulation, of the ventromedial hypothalamic nucleus, the mammillary bodies and the basal, lateral and to a lesser degree, the central nucleus of the amygdaloid complex; the second type--in response to stimulation of the ventral hippocampus, the medial and lateral septum nuclei.     

Change in the functional significance of structures of the cat brain as a result of reorganization of its activity

A study was carried out on 8 adult cats of functional role of the frontal, parietal and occipital parts of the neocortex, and also of the dorsal hippocampus, mediodorsal thalamic nucleus and caudate nucleus head, in realization of a delayed spatial choice (DSCh) before and after compensatory reorganizations of the brain activity caused by multiple electrical stimulation of the frontal part of the cerebral cortex. Compensatory reorganization led to a change of functional significance of these structures. While before this change the frontal cortex, hippocampus and mediodorsal thalamic nucleus were critically necessary brain areas for the realization of the DSCh, after it parietal and occipital cortical areas acquired such significance. The obtained data are discussed proceeding from the principle of the integrity in the brain activity.     

A collector of evoked potentials]

The collector is an adaptive algorithm for pattern recognition. It proposes new in-line fully-automatic technique to learn and recognize effective patterns of input data stream. Evoked potentials (EP) were recorded by ADDA 100 KHz, 4 channels, and described by 200 points per each EP. The collector recognized different studies of conditioned response (CR) by patterns of EPs in amygdalar central nucleus. In dogs with implanted into the limbic structures concentric electrodes an instrumental CR was elaborated to electrical stimulation of the dorsal hippocampus. Generalization or transfer of this CR was tested by means of electrostimulation of amygdalar basal nucleus. The generalization in the first experiment took place approximately in 86% of cases, in the second one in 52% of cases. In the first experiment the amplitudes of initial negativity and of late positive waves were smaller than those in the second one and in the experiments before conditioning.     

Functional organization of the kinesthetic projections of the 1st somatosensory region of the cat cortex

Electrophysiological studies were performed on adult cats under ethaminal anesthesia. Kinesthetic potentials were evoked by passive extension of the ulnar joint and recorded in contralateral primary somatosensory cortical area. Natural (nonelectrical) stimulation of peripheral kinesthetic receptors was performed according to the author's original method. The results obtained show significantly shorter latent period of contralateral kinesthetic potentials in comparison with somatosensory potentials in response to electrical stimulation of the skin. These data demonstrate the possibility of super-rapid conduction of modal-specific volleys to the cortical projection centres in the kinesthetic system of cats.     

Effect of hippocampal stimulation on the feeding behavior of cats

Influence of electrical stimulation (100 cps., 1.0 ms) of medial parts of dorsal and ventral hippocampus (field CA1), and the lateral parts of dorsal and posterior hippocampus (field CA3) on general behaviour, elaboration of instrumental and manifestation of delayed reactions was studied in chronic experiments on cats. Stimulation of medial parts of dorsal and ventral hippocampus elicited a reaction of orienting reflex type to natural stimuli. Stimulation of lateral parts of dorsal and posterior hippocampus evoked arrest reactions. Medial and lateral parts of hippocampus produced different influences on elaboration of conditioned reflexes. In the first case elaboration was possible, but developed slower, while in the second case the ability to learn during stimulation was completely lost due to development of arrest reaction. Stimulation of different parts of the hippocampus disturbed delayed reactions, reducing the number of correct responses.     

Functional Mapping of Dorsal and Median Raphe 5-Hydroxytryptamine Pathways in Forebrain of the Rat Using Microdialysis

Abstract: Recent neurochemical studies of the properties of 5-hydroxytryptamine (5-HT) pathways arising from the dorsal raphe nucleus (DRN) and median raphe nucleus (MRN) have measured extracellular 5-HT in brain regions with reported preferential DRN or MRN 5-HT inputs. Here, we have tested whether electrical stimulation of the DRN and MRN releases 5-HT in rat forebrain regions in a pattern that fits the reported distribution of DRN/MRN pathways. The effect on extracellular 5-HT of electrical stimulation (5 Hz, 300 µA, 20 min) of the DRN, and then MRN, was determined in six regions of the anaesthetised rat. Stimulation of the DRN evoked a short-lasting but clear-cut release of 5-HT (+70–100%) in regions (frontal cortex, dorsal striatum, globus pallidus, and ventral hippocampus) reported to receive a 5-HT projection from the DRN. Regions receiving an MRN innervation (dorsal hippocampus, medial septum, and ventral hippocampus) released 5-HT (+70–100%) in response to MRN stimulation. Regions reported to receive a preferential DRN innervation (frontal cortex, dorsal striatum, and globus pallidus) did not respond to MRN stimulation. Of two regions (dorsal hippocampus and medial septum) reported to receive a preferential MRN innervation, one did not respond to DRN stimulation (dorsal hippocampus) although the other (medial septum) did. In summary, electrical stimulation of the DRN and MRN released 5-HT in a regionally specific pattern. With the exception of one region (medial septum), this pattern of release bears a strong relationship to the distribution of 5-HT projections from the DRN and MRN reported by anatomical studies. The combination of raphe stimulation with microdialysis may be a useful way to study the in vivo neurochemistry of DRN/MRN 5-HT pathways.     

Role of dominant motivation in producing the effects of electric stimulation of hypothalamo-limbic structures

The experiments were made on cats with electrodes chronically implanted in the hypothalamus and the amygdala. The effects of electrical stimulation of the points from which the food reactions were initially evoked, were transformed into an avoidance reaction, if stimulation was applied in surroundings where the animals had previously received pain stimuli. Defensive reactions to stimulation of the hypothalamus and amygdala changed to alimentary reactions if the same stimulation was presented to hungry cats in conditions of repetitive feeding. A conclusion has been drawn that the elements of the hypothalamo-limbic structures have plastic properties and may be involved in different forms of behaviour, depending on current motivation and learning.     

Unit responses of the first and second somatosensory cortical areas to peripheral,thalamic, and cortical stimulation

Unit responses of the first (SI) somatosensory area of the cortex to stimulation of the second somatosensory area (SII), the ventral posterior thalamic nucleus, and the contralateral forelimb, and also unit responses in SII evoked by stimulation of SI, the ventral posterior thalamic nucleus, and the contralateral forelimb were investigated in experiments on cats immobilized with D-tubocurarine or Myo-Relaxin (succinylcholine). The results showed a substantially higher percentage of neurons in SII than in SI which responded to an afferent stimulus by excitation brought about through two or more synaptic relays in the cortex. In response to cortical stimulation antidromic and orthodromic responses appeared in SI and SII neurons, confirming the presence of two-way cortico-cortical connections. In both SI and SII intracellular recording revealed in most cases PSPs of similar character and intensity, evoked by stimulation of the cortex and nucleus in the same neuron. Latent periods of orthodromic spike responses to stimulation of nucleus and cortex in 50.5% of SI neurons and 37.1% of SII neurons differed by less than 1.0 msec. In 19.6% of SI and 41.4% of SII neurons the latent period of response to cortical stimulation was 1.6–4.7 msec shorter than the latent period of the response evoked in the same neuron by stimulation of the nucleus. It is concluded from these results that impulses from SI play an important role in the afferent activation of SII neurons.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 8, No. 4, pp. 351–357, July–August, 1976.     

Attenuation of phrenic motor discharge by phrenic nerve afferents

Short latency phrenic motor responses to phrenic nerve stimulation were studied in anesthetized, paralyzed cats. Electrical stimulation (0.2 ms, 0.01-10 mA, 2 Hz) of the right C5 phrenic rootlet during inspiration consistently elicited a transient reduction in the phrenic motor discharge. This attenuation occurred bilaterally with an onset latency of 8-12 ms and a duration of 8-30 ms. Section of the ipsilateral C4-C6 dorsal roots abolished the response to stimulation, thereby confirming the involvement of phrenic nerve afferent activity. Stimulation of the left C5 phrenic rootlet or the right thoracic phrenic nerve usually elicited similar inhibitory responses. The difference in onset latency of responses to cervical vs. thoracic phrenic nerve stimulation indicates activation of group III afferents with a peripheral conduction velocity of approximately 10 m/s. A much shorter latency response (5 ms) was evoked ipsilaterally by thoracic phrenic nerve stimulation. Section of either the C5 or C6 dorsal root altered the ipsilateral response so that it resembled the longer latency contralateral response. The low-stimulus threshold and short latency for the ipsilateral response to thoracic phrenic nerve stimulation suggest that it involves larger diameter fibers. Decerebration, decerebellation, and transection of the dorsal columns at C2 do not abolish the inhibitory phrenic-to-phrenic reflex.