Double cortical control acting upon activities of intralaminar thalamic cells

We report the effects exerted by the cortex upon the intralaminar thalamic nucleic, as revealed by reversible blockade of the cortex with spreading depression in awake rats. Extracellular recordings of spontaneous activity were made simultaneously at thalamic and cortical sites. The effect of peripheral receptive field stimulation was to decrease activity of intralaminar thalamic cells. Cortical recordings revealed the cortical regions affected by spreading depression. Two type of cells were identified depending on the changes in their sensorial responses during the cortical spreading depression propagation. The first exhibited a tonic facilitating cortical control when the cortical spreading depression was located at A 8.0 to A 10.0. The second type exhibited a disappearance of the sensorial responses when cortical spreading depression was located at A 4.0 to A 8.0 and also displayed the tonic facilitating control. This indicates that two different identified cortical regions influenced the thalamic activity.     

Spreading depression elicited by thermal effects of ultrasonic irradiation of cerebral cortex in rats

Cortical spreading depression (CSD) was elicited by focused ultrasonic irradiation (800 kHz) of exposed cerebral cortex in anesthetized rats. With the acoustic output of 0.65 W at the probe-tissue contact (3 mm in diameter), CSD was elicited after 28-sec irradiation in normothermic rats. Reduction of cortical temperature to 31°C increased the threshold irradiation time to 82 sec on the average. Ten- to thirty-sec heating of cerebral cortex with a thermode elicited CSD when surface temperature exceeded 47°C. Histological examination of the cortical areas exposed to threshold irradiation revealed a central coagulation lesion surrounded by edema. It is concluded that the ultrasonic irradiation elicits CSD by dissipated heat. Differences in threshold duration of irradiation in hypothermic and normothermic rats were used to compute the threshold temperature which had to be exceeded in the critical volume of cortex in order to start CSD.     

The effect of cortical spreading depression on motor performance and depth avoidance in rats.

Functional decortication induced by cortical spreading depression (CSD) was used to estimate the significance of cerebral cortex for swimming and depth avoidance in arts. In the swimming test (5 gr sinkers, 36 degrees C water) the median swimming time was reduced from greater 120 minutes in the controls to 16 minutes in the bilaterally depressed rats. Depth avoidance in the physical and visual cliff situation (6 cm to the shallow and 48 cm to the deep surface) was unimpaired by unilateral CSF but was abolished by bilateral CSD. Combination of monocular occlusion with ipsilateral CSD deteriorated the visual cliff test but not the physical cliff behaviour. Functional decortication increased descent latencies and decreased the explaration rate in both tests. It is concluded that cerebral cortex plays an important role in the regulation of unlearned, innate activities with the overall behaviour of the organism.     

Localisation of the origin of self-sustained after-discharges (SSADs) in the rat: the serrated wave (SerW) type of SSAD

The self-sustained after-discharges (SSADs) characterised by the EEG pattern of serrated waves (SerW) were induced by rhythmic low frequency electrical stimulation of thalamic nuclei and the hippocampus of Wistar albino male rats in acute experiments. We used spreading depression to eliminate functionally the cortex and the hippocampus. Suction ablation of the cortical somatosensory projection area was also used to test its involvement in the SerW SSAD induction. The hippocampal spreading depression but not the cortical one abolished the SerW SSAD induced by the stimulation of the thalamic nuclei. The animals with the suction ablation of the somatosensory projection area also produced SerW SSADs when the stimulation electrodes were placed in the thalamic ventrobasal complex (in intact animals this stimulation induces spike-and-wave SSADs but not SerW-SSAD). The crucial importance of the hippocampus in the SerW SSAD generation and its possible use as a model of partial seizures with complex symptomatology is discussed.     

Cortical afterdischarges during Leao's cortical spreading depression.

Cortical spreading depression (CSD) has been employed in unanesthetized curarized rats, in order to analyse the role of the cerebral cortex in the generation of epileptic self-sustained parozysms produced by direct cortical electrical stimulation. CSD was preferred because it is reversible and may be repeated several times in the same animal. CSD evoked in the hemisphere contralateral to the stimulated cortex decreased the duration of the afterdischarge by 40% and modified its form and amplitude both at the cortical and reticular levels. The possible role of cortical and subcortical structures in the development of after-discharges is discussed.     

Peculiarities of Development of the Depression State in Rats Characterized by Different Individual/Typological Behavioral Statuses

We examined the development of a depression state induced by long-lasting stressing of rats preliminarily selected according to their active or passive behavior pattern. Stress was induced using a technique of sensory contact with aggressive individuals. The pathologically modified state in animals of the above groups developed according to dissimilar scenarios. As a result, a depressive state similar to anxious depression developed in active animals, while psychoemotional disorders similar to a melancholy-type depression were formed in passive rats. Therefore, the symptomatic heterogeneity of depression is, to a considerable extent, determined by individual/typological peculiarities of behavior (passive vs active) and can be rather clearly identified using the sensory contact technique.     

Spectrin and calmodulin in spreading mouse blastomeres

The role of spectrin and its association with calmodulin in spreading mouse blastomeres was investigated. Embryonic spectrin binds 125I-calmodulin in a calcium-dependent fashion in the blot overlay technique. Double-labeling experiments show coordinate redistribution of spectrin and calmodulin in blastomeres preparing to undergo active spreading movement. At this stage cortical spectrin staining is lost from the region of cell-substrate contact and spectrin and calmodulin become concentrated in two structures closely associated with the contacted region: a group of spherical bodies located on the cytoplasmic side of the cortical layer and a subcortical ring that marks the perimeter of the contacted region. The localization pattern of spectrin and calmodulin is also coordinated with that of actin and myosin. The results suggest that spectrin plays a role in the spreading of blastomeres and that this function may involve linkage of spectrin, calmodulin, and the cortical contractile apparatus.     

Properties of spreading depression during different phases of cyclic excitation of the rat neocortex

Properties of cortical spreading depression were studied during different phases of cyclic excitation developing in the neocortex of rats under the influence of low-frequency electrical stimulation. Waves of spreading depression appeared in the cortex spontaneously or after microinjection of potassium chloride. During each excitation cycle a state preventing the passage and appearance of these waves developed in the region of electrical stimulation. The degree of blocking in other areas of the cortex outside the region of stimulation depended on the distance from the site of electrical stimulation and on generalization of excitatation over the cortex. After the end of the excitation phase, while the current continued to act, the ability of the cortex to conduct the depression wave was restored. In intervals of cyclic excitation the duration of the waves of spreading depression remained on average only half its duration in the absence of stimulation. The time course of development and the character of recovery of depression during the intervals confirm the hypothesis that activation of the potassium-sodium pump may have a role in the blocking mechanism and enable the temporal parameters of this process to be estimated.     

Rhythmic metrazol activity and cortical spreading depression

The incidence of segments of rhythmic metrazol activity (RMA) in cortical leads and in the thalamus and hippocampus was studied in acute experiments on nine male albino laboratory rats. First of all we studied activity after administering metrazol in an i.p. dose of 50 mg/kg, without any further treatment, and then, after a control recording, we induced cortical spreading depression and observed its effect on the incidence and synchronization of RMA in the individual leads. We came to the conclusion that the thalamus is incapable of isolated production of RMA. The cortex is able to produce RMA without participation by the studied structures of the specific thalamus and hippocampus; RMA probably originates in the cortex itself. Generalization is impaired, but not eliminated, by a cortical block. The hippocampus independently produces another type of rhythmic activity.     

On the mechanism of the inhibitory effect of potasium ions on amino acid incorporation into rat cerebral cortex proteins in vivo.

Earlier results on potassium ion inhibition of amino acid incorporation into the brain proteins in vivo (spreading cortical depression) led to the hypothesis that inhibition of protein synthesis is based on ATP deficiency. In the present study we tested various aspects of the aminocylation of tRNA, an ATP-dependent process, during spreading cortical depression produced by the topical application of 25% KCl. On using a 7-min interval between the subcutaneous injection of L-[U-14C] leucine and killing the rat, incorporation into the tRNA fraction was found to be reduced by 25%. Total amino acid radioactivity in the soluble fraction was unaltered. The acceptor capacity of tRNA, measured in vitro, and the proportion of non-acylated tRNA in vivo were likewise unchanged.     

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

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

State of the epiphysis during winter hibernation]

It was found that the pineal gland of active ground squirrels (Citellus erythrogenys) differed from this gland in rats by a more pronounced differentiation into cortical and medullary zones, by larger pineocytes with polymorphous nuclei and numerous pseudokariosomes. Hybernation was accompanied by reduced concentration of serotonin in the pineal gland, by the disappearance of differences between the cortical and the medullary zones and by a number of morphological signs of functional depression. The appearing changes were similar to those occurring in denervation of the pineal gland.     

A mathematical model for spreading cortical depression.

A mathematical model is derived from physiological considerations for slow potential waves (called spreading depression) in cortical neuronal structures. The variables taken into account are the intra- and extracellular concentrations of Na+, Cl-, K+, and Ca++, together with excitatory and inhibitor transmitter substances. The general model includes conductance changes for these various ions, which may occur at nonsynaptic and synaptic membrane together with active transport mechanisms (pumps). A detailed consideration of only the conductance changes due to transmitter release leads to a system of nonlinear diffusion equations coupled with a system or ordinary differential equations. We obtain numerical solutions of a set of simplified model equations involving only K+ and Ca++ concentrations. The solutions agree qualitatively with experimentally obtained time-courses of these two ionic concentrations during spreading depression. The numerical solutions exhibit the observed phenomena of solitary waves and annihilation of colliding waves.     

Insulin Stimulates Phosphatidylinositol 3-Kinase Activity in Rat Neuronal Primary Cultures

Abstract: The effect of cortical spreading depression (CSD) on cerebral protein synthesis (CPS) was examined. CSD was evoked in normal rats with KCI, and CPS was measured autoradiographically with [1-¹⁴C]leucine. Average rates (mean ± SD) of CPS in layers I-IV of cortex decreased significantly from 10.7 ± 0.6 (sham-operated controls; n = 4) to 6.7 ± 0.7 nmol/g/min (n = 4; p < 0.01) and in layers V-VI from 10.9 ± 0.5 to 9.4 ± 0.4 nmol/g/min (p < 0.05) during 60 min of repetitive CSD. Spreading depression did not affect CPS rates in other subcortical brain regions. These results indicate that KCl-evoked CSD induces inhibition but not suppression of cortical protein synthesis.     

Functional hemidecortication by spreading depression or by focal epileptic discharge disrupts spatial memory in rats

The importance of neocortex for the acquisition and retrieval of the water tank navigation task has been examined in 110 hooded rats. The animals were trained to swim to a small (10 cm in diameter) submersed platform 1 cm below the surface of a large pool (120 cm in diameter) of opaque water. In Experiment 1, naive rats with unilateral cortical spreading depression (SD) elicited by application of a filter paper soaked with 25% KC1 on one hemicortex were unable to find the platform during 1 min in about 50% of the 12 acquisition trials. The performance of functionally hemidecorticated rats did not improve after a single trial with the intact brain, but escape latencies were significantly shortened in rats given 2,6 or 60 pretraining trials with intact brain. Even in the overtrained rats escape latencies under unilateral SD were significantly longer (14 sec) than in intact rats after 12 acquisition trials (5 sec). In Experiment 2, development of an epileptic focus established by local penicillin application onto the exposed cortical surface was electrophysiologically monitored. Regular interictal discharge (0.2 to 0.5 Hz) disrupted acquisition of the navigation task and interfered to a lesser degree with performance in rats given 12 and 36 pretraining trials with the intact brain. The occipital foci were more disruptive than the frontoparietal ones. Performance recovered with cessation of the epileptic discharge. It is concluded that spatial memory mediating navigation in the water tank task requires coordinated activity of both cerebral hemispheres.     

Polar body formation in Spisula oocytes: function of the peripheral aster

Activated Spisula oocytes proceed through meiotic stages rapidly and in near synchrony, providing an excellent system for analyzing polar body formation. Our previous studies suggested that cortical spreading of the metaphase peripheral aster determines spatial features of the cortical F-actin ring that is generated prior to extrusion of the polar body. We tested this hypothesis by experimentally altering the number and cortical contact patterns of peripheral asters. Such alteration was achieved by (a) lovastatin-induced arrest at metaphase I, with and without hexylene glycol modification, followed by washout; and (b) cytochalasin-D inhibition of extrusion of the first polar body, with washout before extrusion of the second polar body. Both methods induced simultaneous formation of two or more cortically spreading asters, correlated with subsequent formation of double, or even triple, overlapping F-actin rings during anaphase. Regardless of pattern, ring F-actin was deposited near regions of greatest astral microtubule density, indicating that microtubules provided a positive stimulus to which the cortex responded indiscriminately. These results strongly support the proposed causal relationship between peripheral aster spreading and biogenesis of the F-actin ring involved in polar body formation.     

Hippocampus-dependent retrieval and hippocampus-independent extinction of place avoidance navigation,and stress-induced out-of-context activation of a memory revealed by reversible lesion experiments in rats

The use of reversible lesion techniques in memory research was pioneered in the laboratory of Jan Bures and Olga Buresova. We use the occasion of Jan's 75th birthday to briefly review the experimental utility of this approach. Two experiments from our current research are reported in which reversible lesioning methods are used to ask otherwise experimentally untenable questions about memory retrieval. The first experiment used intra-hippocampal injections of tetrodotoxin to temporarily inactivate the hippocampus during retrieval of a well-learned place avoidance navigation memory. This revealed that the hippocampus is necessary for place avoidance retrieval but that the extinction of place avoidance can occur independently of retrieving the memory and intact hippocampal function. The second experiment used KCl-induced cortical spreading depression in an interhippocampal transfer paradigm to demonstrate that a Y-maze memory that is learned by only one cortical hemisphere can be made to transfer to the other hemisphere by forcing the rat to swim, a unique stressful experience that occurred in a different apparatus, different behavioral context, and involved different behaviors than the Y-maze training. This demonstrates, we believe for the first time behaviorally, that memories can be activated outside of the behavioral context of their acquisition and expression in rats.     

Influence of Ovarian Hormones on Cortical Spreading Depression and Its Suppression by L-kynurenine in Rat

Migraine is sexually dimorphic and associated in 20–30% of patients with an aura most likely caused by cortical spreading depression (CSD). We have previously shown that systemic L-kynurenine (L-KYN), the precursor of kynurenic acid, suppresses CSD and that this effect depends on the stage of the estrous cycle in female rats. The objectives here are to determine the influence of ovarian hormones on KCl-induced CSD and its suppression after L-KYN by directly modulating estradiol or progesterone levels in ovariectomized rats. Adult female rats were ovariectomized and subcutaneously implanted with silastic capsules filled with progesterone or 17β-estradiol mixed with cholesterol, with cholesterol only or left empty. Two weeks after the ovariectomy/capsule implantation, the animals received an i.p. injection of L-KYN (300 mg/kg) or NaCl as control. Thirty minutes later CSDs were elicited by applying KCl over the occipital cortex and recorded by DC electrocorticogram for 1 hour. The results show that both estradiol and progesterone increase CSD frequency after ovariectomy. The suppressive effect of L-KYN on CSD frequency, previously reported in normal cycling females, is not found anymore after ovariectomy, but reappears after progesterone replacement therapy. Taken together, these results emphasize the complex role of sex hormones on cortical excitability. The CSD increase by estradiol and, more surprisingly, progesterone may explain why clinically migraine with aura appears or worsens during pregnancy or with combined hormonal treatments.     

Binding of (3)-imipramine by platelets from spontaneously hypertensive, normotensive, and Wistar rats and their behavior in stressful situations]

Spontaneously hypertensive rats (SHR), when submitted to stress remained active during both avoidance (water escape task test) and nonavoidance (forced swimming test) stress-situations. Wistar rats responded to a depression of active behaviour in forced swimming test and difficulty at resolving of complicated problem in water escape task test. did not differ in the affinity but the number of binding sites of 3H-imipramine was greater in SHR. SHR rats had a smaller number of binding sites that Wistar ones.     

Blockade of corticoliberin receptors prevents development of poststressor psychopathology in rats with active strategy of adaptive behaviour

Active as well as passive Wistar rats were subjected to a single water-immersion action that gave rise signs of poststressor depression in them. Administration of CRH-R1-receptor peptide blocker astressin prevented development of behavioural deficiency in active rats and did not affect behaviour of passive rats. This suggests that the corticoliberin receptor blockers are only effective for treatment of poststressor depressions in individuals with initially behavioural strategy.