Effects of distant transplantation of the embryoniclocus coeruleus on the learning process and memory in rats

We studied the effects of distant transplantation (in the neck region, subcutaneously) of the embryoniclocus coeruleus tissue on the indices of the learning process and memory in recipient rats. The patterns of learning for a conditioned emotional avoidance reaction (CEAR) allowed us to classify experimental animals into two groups, with successful and hampered formation of the CEAR sterotype, respectively. In the first-group rats, after formation of this stereotype we electrolytically injured the frontal brain cortex, which resulted in some worsening of the CEAR reproduction and quality of differentiation. Distant transplantation of thelocus coeruleus tissue provided effective recovery of the CEAR reproduction in the first-group animals, while rather fast and successful formation of the CEAR stereotype became possible in the second group of rats. It is concluded that the transplantedlocus coeruleus tissue preserves its viability, undergoes differentiation, and exerts a stimulating influence on the learning process and memory formation (probably, due to activation of noradrenergic links in the brain systems).     

Effects of blockade of noradrenergic and serotonergic transmission in theCM-Pf complex on neuronal activity in the motor thalamus in cats

Effects of injections of blockers of the monoaminergic receptor structures into thecentrum medianum-nucl. parafascicularis (CM-Pf) on the activity of neurons in the motor thalamic nuclei (VA-VL) were studied in chronic experiments on awake cats. The animals were trained to perform an operant placing reflex by the forelimb. Injection of a-adrenoblocker, anapriline, into theCM-Pf resulted in enhancement of background activity of neurons of the motor thalamus and facilitation of their spike responses related to conditioned and unconditioned reflex movements. Application of a blocker of serotonin receptors, lysergoamide, evoked opposite changes in the neuronal activity in theVA-VL nuclei: depression of background activity, facilitation of inhibitory processes, and suppression of evoked activity related to conditioned and unconditioned movements. It is supposed that the monoaminergic system of thelocus coeruleus exerts a suppressing influence on the motor thalamus via theCM-Pf complex, while the system of the raphe nuclei facilitates motor thalamic structures.Neirofiziologiya/Neurophysiology, Vol. 28, No. 6, pp. 305–311, November–December, 1996.     

One of the Pathways of Transmission of Afferent Activity to the Locus Coeruleus Under Conditions of Immobilization Stress

An electrophysiological proof has been obtained for the morphological data on the existence of afferent inputs from the medullary nucl. praepositus hypoglossi (NPH) to the brainstem locus coeruleus. The crucial role of the NPH in the formation of background spike activity of neurons of the locus coeruleus under conditions of short-term immobilization stress has been demonstrated. Neirofiziologiya/Neurophysiology, Vol. 37, No. 2, pp. 151–156, March–April, 2005.     

Action of cortical extracts of the left and right hemispheres on the recovery of conditioned reflex activity in rats after unilateral removal of the frontal cortex

The recovery of active avoidance conditioned reflex (AACR) was investigated after unilateral frontal cortex extirpation. Intraperitoneal injection of extracts from left or right brain cortex (1 mg/kg) of healthy rats (LE or RE) stimulated AACR recovery in animals with lobectomy on the same side. If RE was extracted 9 days after left side brain extirpation, i.e. during the period of the development of compensatory processes, its effect on AACR recovery was stronger in left-operated animals, while in right-operated animals it remained unchanged.     

Effects of Fat-Enriched Diet on the Content of Sphingolipids in the Brain and on Cognitive Functions in Old Rats

It was demonstrated that levels of free fatty acids and radioactively labeled ([¹⁴C]) ceramide in the liver, muscles, and brain of rats fed a saturated fat-enriched diet for 36 weeks (from 15 to 24 months) increased, as compared with the corresponding levels in control animals of the same age (24 months old). A high-saturated fat diet resulted in a rise in the content of sphingolipids synthesized de novo in the neocortex and hippocampus of 24-month-old rats. High levels of ceramide and sphingosine in the neocortex and hippocampus induced in these rats by the above diet correlated with considerable worsening of the conditioned reflex activity of animals (reflex of active avoidance in the shuttle chamber).     

The influence of BT-melanin on the recovery of conditioned instrumental reflexes in rats surviving after ablation of the sensorimotor cortex

It has been shown the reinforcement of the corticofugal plasticity in adult rats after unilateral ablation of sensorimotor cortex accompanied by intramuscular injections of low concentrations of BT-melanin. In result the process of compensatory recovery in rats central nervous system is accelerated, confirmable by the rapid recovery of previously elaborated instrumental conditioned reflex in comparison with the control animals. It is assumed that the compensation of the motor deficit arised after the sensorimotor cortex ablation is ensured by the ability of two main motor systems of the brain (corticospinal and corticorubrospinal) to duplicate each other. This phenomenon of functional switching of descending influences has also been revealed in control group rats, not injected with BT-melanin. However the difference in time periods of operantly conditioned reflex recovery, for experimental and control groups, argues the apparent acceleration of this process, induced by the effects of BT-melanin. The obtained data considers the possibility of applied use of low concentrations of BT-melanin.     

Level of neuroactive steroids in the brain and sex-related peculiarities of formation and extinction of conditioned reflex in rats

Sex-related peculiarities of dynamics of brain sex steroids in the process of learning and extinction of the conditioned reflex of passive avoidance have been studied in model experiment. Prior to learning of the conditioned reflex, female rats were found to be distinguished by manifestation of anxiety and fear as compared with male rats. At formation of the conditioned reflex, no significant sex-related differences were detected between males and females, whereas extinction of the conditioned reaction of passive avoidance in males occurred by 2–3 days faster than in females. At learning of conditioned reaction of passive avoidance, in sexually mature male rats there was revealed an increase of the testosterone content in various brain structures, especially in hippocampus and frontal cortex, while its level in blood plasma remained unchanged. Also shown was an elevation of estradiol concentration in female amygdale, whereas at extinction of the conditioned reaction of passive avoidance, a rise of estradiol values was noted in hippocampus and cingular cortex. At the same time, the testosterone level in blood plasma did not change, whereas after extinction of the conditioned reflex the estradiol concentration decreased statistically significantly. Different dynamics of changes of the sex steroid levels in brain and blood plasma can indicate a possibility of their formation in the nervous tissue. The performed correlation analysis confirms the concept of selective involvement of testosterone and estradiol of individual brain structures in realization of processes of learning and memory in sexually mature male and female rats.     

Effect of an analog of vasopressin on the fixation of temporary connections in the intact rat and after destruction of the locus coeruleus

Subcutaneous injection to intact rats and rats with destroyed locus coeruleus of 10 mcg of triglycide-glycinamide-lysinevasopressin (TGDGA-LVP) immediately after elaboration of labyrinth defensive conditioned reflex improves consolidation of temporary connections and raises its resistance to extinction. Improved consolidation of temporary connection is retained in animals with destroyed locus coeruleus for a shorter time than in intact animals. At the same time according to some characteristics, TGDGA-LVP has a more expressed influence of positive character on animals with destroyed locus coeruleus than on intact rats.     

The asymmetry of the free amino acid pool in sections of the rat brain

The content of free amino acid pool in symmetric regions of cortex, hypothalamus, midbrain and blood of rats which had produced the movement conditioned reflex strengthened by feeding was studied. It was established that the "untrained" rats have higher content of free amino acid pool in their blood. The brain of the experimental animals revealed the biochemical asymmetry which was marked by the differences in free amino acid pool distribution between the left and right halves of the studied regions of brain. It was shown that left sided asymmetry animals i.e. animals with heightened content of free amino acid pool in the left half of the brain dominated in the "untrained" group of rats. The supposition was expressed that this biochemical asymmetry may contribute to the ability of animals to learn.     

Role of monoamines in the recovery of the conditioned reflex activity of rats following extirpation of the frontal cortex

The influence of frontal cortex extirpation on the amount of monoamines in the brain structures was investigated in chronic experiments on rats trained according to the method of motor feeding reflexes with bilateral reinforcement. Monoamine levels were measured by high performance liquid chromatography with electrochemical detection. By the ninth day after the ablation serotonin (5-HT) and dopamine (DA) levels were significantly reduced in the cortex and the striatum, respectively, while noradrenaline ++ (NA), 5-HT, dihydroxyphenylacetic and 5-hydroxyindoleacetic acid levels in raphe nuclei and locus coeruleus were increased. The level of conditioned reflex reproduction was 39% on the light and 33% on the sound stimulus. The involvement of monoamines in the recovery of conditioned reflexes after frontal cortex extirpation is discussed.     

Trypanosoma evansi: Adenosine deaminase activity in the brain of infected rats

The study was undertaken to evaluate changes in the activity of adenosine deaminase (ADA) in brains of rats infected by Trypanosoma evansi. Each rat was intraperitoneally infected with 10⁶ trypomastigotes either suspended in fresh (group A; n = 13) and cryopreserved blood (group B; n = 13). Thirteen animals were used as control (group C). ADA activity was estimated in the cerebellum, cerebral cortex, striatum and hippocampus. No differences (P > 0.05) in ADA activity were observed in the cerebellum between infected and non-infected animals. Significant (P < 0.05) reductions in ADA activity occurred in cerebral cortex in acutely (day 4 post-infection; PI) and chronically (day 20 PI) infected rats. ADA activity was significantly (P < 0.05) decreased in the hippocampus in acutely infected rats, but significantly (P < 0.05) increased in the chronically infected rats. Significant (P < 0.05) reductions in ADA activity occurred in the striatum of chronically infected rats. Parasites could be found in peripheral blood and brain tissue through microscopic examination and PCR assay, respectively, in acutely and chronically infected rats. The reduction of ADA activity in the brain was associated with high levels of parasitemia and anemia in acute infections. Alterations in ADA activity of the brain in T. evansi-infected rats may have implications for pathogenesis of the disease.     

Neuron activities of the motor cortex during conditioned eye blink reflex in rabbits (author's transl)]

Effects of the tone (CS) on neurons of the motor cortex were investigated in naive, pseudoconditioned, and conditioned rabbits. Conditioning to eye blink reflex was made by a combination of CS and air puff (US). Effects of electrical stimulation of the subcortical structures were also observed on the cortical neurons associated with the conditioned reflex. The results were as follows. (1) Proportion of neurons which significantly increased the firing rate in response to the CS, type E, was higher in the conditioned group than in other two groups. On the other hand, no group difference was found in the proportion of neurons which significantly decreased the firing rate to the stimulus, type I. (2) Most of the type E neurons in the conditioned rabbits began to fire at latencies of about 50 to 100 msec after the CS, preceding about 200 msec to the appearance of the peripheral conditioned responses (EMG). (3) Most of the type E neurons in the conditioned animals were more easily affected by stimulation of the medial geniculate body and the brain stem reticular formation. Based on the results mentioned above, it is concluded that in the rabbits conditioned to the eye blink reflex, excitability of neurons in the motor cortex is enhanced by the tone (CS), and by electrical stimulation to the medial geniculate body and the brain stem reticular formation.     

Secretin Activates Visceral Brain Regions in the Rat Including Areas Abnormal in Autism

1. The aim of this study was to determine whether central networks are involved in the presumptive behavioral and autonomic regulatory actions of secretin, a gut hormone that has been reported to have ameliorative effects in autistic children.2. Central neural responses monitored by regional c-fos gene expression were examined in response to intracerebroventricular secretin injection in awake, freely-moving Sprague-Dawley rats. Tissue sections were incubated in an antibody to the c-fosgene product, Fos, and processed immunohistochemically.3. Qualitative differences in Fos immunoreactivity in stress adaptation and visceral representation areas of the brain were observed between secretin- and vehicle-infused age-matched pairs (n = 4 pairs). Secretin-activated regions include the area postrema, dorsal motor nucleus, medial region of the nucleus of the solitary tract and its relay station in the lateral tegmentum, locus ceruleus, ventral periaqueductal gray, periventricular thalamic nucleus, paraventricular hypothalamus magnocellularis, medial and central amygdala, lateral septal complex as well as ependymal and subependymal nuclei lining the third ventricle. Specific areas of the cerebral cortex were heavily labeled in secretin-treated rats, as compared to controls: the medial bank of the anterior prefrontal cortex, orbitofrontal cortex, the piriform cortex, and the anterior olfactory nucleus. Secretin attenuated Fos immunoreactivity in the dorsal periaqueductal gray, intralaminar thalamus, medial parvicellular compartment of the hypothalamus, supraoptic nucleus of the hypothalamus, lateral amygdala, motor cortex, and the somatosensory and association areas of the parietal cortex.4. Secretin alters the activity of structures involved in behavioral conditioning of stress adaptation and visceral reflex reactions. This study predicts a possible cellular mechanism, activation of third ventricular ependymal and subependymal cells, as well as central regulatory actions of secretin. The physiological effects of secretin on behavioral, endocrine, autonomic and sensory neuronal activation patterns, together, contribute to central c-fos activation. Secretin alters the activity of structures involved in behavioral conditioning of stress adaptation and visceral reflex reactions. This study predicts a possible cellular mechanism, activation of third ventricular ependymal and subependymal cells, and central regulatory actions of secretin. The physiological effects of secretin on behavioral, endocrine, autonomic and sensory neuronal activation patterns, together, contribute to central c-fos activation. These findings mandate further investigation of secretin as a brain/gut stress regulatory hormone.     

Level of neuroactive steroids in the brain, and gender-related differences in formation and decrease of conditioned reflex in rats

We investigated gender-related differences in dynamics of the brain sexual steroids during learning and the decrease of conditioned reflex in the modeling experiment. It was revealed that, before training to conditioned reflexes, females manifested a greater anxiety than males. Significant differences between males and females in formation of the conditioned reflex of passive avoidance were not revealed, whereas the conditioned response decrease were by 2-3 days faster in male rats than in females. It was revealed that there was an increase of testosterone content in various structures of the brain, especially in hippocampus and frontal cortex with its constant level in the blood plasma in learning conditioned response of passive avoidance in male adult rats. Also an increased estradiol concentration was found in females' amygdale, while increased value of estradiol was detected in hippocampus and the singular cortex in decrease of the conditioned response of passive avoidance. In blood plasma, the testosterone level was not changed, and the estradiol concentration was reduced significantly after the decreased conditioned reflex. Different dynamics of changes in the levels of sex steroids in the brain and the blood plasma can indicate a probability of their formation in nervous tissue. The correlation analysis confirms the conception about selective involvement of the brain's testosterone and estradiol in the specific structures in realization ofthe learning and memory processes in adult male and female rats.     

Detection and localization of a putative cyclic-GMP-activated channel protein in the protozoan ciliate Stentor coeruleus

Summary. Immunoblotting and immunocytochemical assays were employed to identify and localize a channel protein activated by cyclic GMP (cGMP) in the protozoan ciliate Stentor coeruleus. Analysis of whole-cell homogenate with antibodies raised against the α-subunit of the cGMP-activated channel protein from bovine rod outer segments and against cGMP revealed four major protein bands with molecular masses of 40 kDa, 63 kDa, and over 120 kDa, which bound cGMP. However, only a cGMP-binding protein of 63 kDa, corresponding to the α-subunit of the cGMP-activated ion channel protein from bovine rod outer segments, was found in the ciliate cortex fraction. The functional cGMP-activated channel protein was also shown to be present in the cortex fraction of S. coeruleus by patch-clamp measurements of artificial liposomes. Incorporation of the cortex fraction into liposomes resulted in the appearance of ion channel activity related to cGMP. The reconstituted protein channels were strongly inhibited by l-cis-diltiazem, a known potent blocker of many types of cyclic-nucleotide-activated channels. The results presented here are the first demonstration of the existence and localization of a putative cGMP-activated channel protein in the ciliate S. coeruleus. Cyclic-nucleotide-activated channel proteins are nonspecific cation channels which mediate the receptor potentials in photoreceptor cells and in cells of the olfactory epithelium. On the basis of these data, we suggest that the 63 kDa protein identified in Stentor coeruleus is also a cGMP-activated ion channel and that it may be involved as an effector in the photosensory transduction pathway leading to the motile photophobic response in this ciliate protist. Correspondence and reprints: Department of Cell Biology, Nencki Institute of Experimental Biology, 3, Pasteur ulica, 02 093 Warsaw, Poland.     

Analysis of the level of cyclic adenosine-3',5'-monophosphate in structures of the 'informational' and 'motivational' system of the rat brain during active conditioning

The content of cyclic adenosine-3',5'-monophosphate (cAMP) was studied in structures of the "motivational" and "infromational" systems of rat brain after the active avoidance conditioning procedure in rats. Three groups of animals were examined: naive rats, trained (conditioned) rats, and group of the active control presented with uncombined conditioned (light) and unconditioned (electric footshock) stimuli. The content of cAMP was determined in the frontal cortex, hippocampus, amygdala, and hypothalamus of both hemispheres immediately after the retrieval of conditioned reaction one day after conditioning. A significant increase in cAMP level was bilaterally observed in the hypothalamus in the group of active control, and in both hippocampi and the right frontal cortex in the conditioned animals. Positive correlations between the cAMP levels in symmetrical regions of the frontal cortex, amygdala, and hypothalamus were revealed in all the examined groups. Additionally, intra- and interhemispheric correlations were found in the active control and conditioned rats. Patterns of correlation were specific for each of these groups. The observed phenomenon is discussed in term of involvement of "informational" and "motivational" brain structures in the mechanisms of adaptive behavior.     

Sodium oxybutyrate and piracetam acceleration of the compensatory-reparative processes after damage to the cerebral cortex in rats

The effects of sodium hydroxybutyrate and piracetam on compensatory-reparative processes in the central nervous system have been investigated in rats after extirpation of the frontal cortex. The animals were pretrained to conditioned reflex of active avoidance. Extirpation of the frontal cortex has been shown to disturb the conditioned reflex. Sodium hydroxybutyrate (50 mg/kg) and piracetam (200 mg/kg) were found to precipitate the recovery of the damaged reflexes.     

Protective Effects of Nigella sativa on the Neuronal Injury in Frontal Cortex and Brain Stem After Chronic Toluene Exposure

The goal of this study was designed to evaluate the possible protective effects of Nigella sativa (NS) on the neuronal injury in the frontal cortex and brain stem after chronic toluene exposure in rats. The rats were randomly alotted into one of three experimental groups: A (control), B (toluene treated) and C (toluene treated with NS); each group contain 10 animals. Control group received 1 ml serum physiologic and toluene treatment was performed by inhalation of 3,000 ppm toluene, in a 8 h/day and 6 day/week order for 12 weeks. The rats in NS treated group was given NS (in a dose of 400 mg/kg body weight) once a day orally by using intra gastric intubation for 12 weeks starting just after toluene exposure. Tissue samples were obtained for histopathological investigation. To date, no histopathological changes of neurodegeneration in the frontal cortex and brain stem after chronic toluene exposure in rats by NS treatment have been reported. In this study, chronic toluene exposure caused severe degenerative changes, shrunken cytoplasma, severely dilated cisternae of endoplasmic reticulum, markedly swollen mitochondria with degenerated cristae and nuclear membrane breakdown with chromatin disorganization in neurons of the frontal cortex and brain stem. The nerve cells showing the pathologic changes were almost absent in the NS-treated rats. We conclude that NS therapy causes morphologic improvement on neurodegeneration in frontal cortex and brain stem after chronic toluene exposure in rats. We believe that further preclinical research into the utility of NS may indicate its usefulness as a potential treatment on neurodegeneration after chronic toluene exposure in rats.     

Transplantation of embryonic nerve tissue from the preoptic region: Effects on coordination of ovarial,locomotor, and temperature biorhythms in rats

Motor activity and changes in body temperature related to the alternation of stages of an estrous cycle were studied in albino rats; groups of animals with the intact preoptic region (RPO), with electrolytically destroyedRPO, and with lesion of this structure followed by a transplantation of the embryonicRPO tissue were compared. It is hypothesized that the changes in hormonal background level related to the stages of estral cycles and controlled with the involvement of theRPO determine the amplitude of infradian cyclic variations of motor activity and body temperature, but do not initiate these rhythms.Neirofiziologiya/Neurophysiology, Vol. 26, No. 4, pp. 283–290, July–August, 1994.     

Activity of the parietal associative cortex neurons and aminergic brainstem neurons at the performance of a voluntary movement in cats

Activity of 98 neurons of the parietal associative cortex (PAC) and 189 supposedly aminergic brainstem neurons (dopaminergic in thesubstantia nigra pans compacta, noradrenergic in thelocus coeruleus region, and serotonergic in theraphe nuclei) was recorded in awake cats. The animals were trained to perform a voluntary movement (pressing a pedal) not earlier than at a certain prefixed time moment. More than half of the recorded units modified their activity before the movement initiation. The PAC neurons responded mostly within the interval of planning of the movement, while reactions of aminergic neurons were observed in the course of its initiation, which probably provides facilitation of the responses of cortical neurons. The pattern of responses was rather specific for each of the studied neuronal populations.