Formation of the conditioned reflexes to a complex signal in ontogenesis under alternate choice conditions

The formation of a conditioned reflex to a complex signal, “light+sound,” and its components under alternate choice conditions was studied in kittens aged 1.5–10 months. A preference for one of the food dispensers and a low percent of correct reactions (48–57%) was characteristic during the process of training for kittens aged from 1.5 to 5 months. Successful training using the alternate choice, method was achieved in kittens whose training began at six months of age. A lesion of the sensorimotor region of the cortex in the same kittens following the achievement of a high level of correct reactions (75–80%) led to a disturbance in the previously developed reflex to the complex signal and its components. The latter was expressed in the manifestation of unidirectional motoric reactions and a sharp decrease in the percent of correct reactions. The question of the confinement of the development of different forms of interaction of the sensory and motor systems to specific age periods and the participation in this process of the sensorimotor region of the cortex is discussed. A. A. Ukhtomskii Scientific Research Institute of Physiology, Saint Petersburg State University. Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti imeni I. P. Pavlova, Vol. 45, No. 2, pp. 289–296, March–April, 1995.     

Influence of extirpation of the sensorimotor area of the cortex on the formation of conditioned reflexes in response to a complex signal in the ontogenesis of the cat

The influence of the extirpation of the sensorimotor cortex (SMC) on the formation and maintenance of a previously developed alimentary conditioned reflex to a simultaneous complex stimulus (light+sound) with extinction of the reaction to unreinforced components of the complex signal was studied in kittens aged 39 days to 4 months. The extirpation of the SMC prior to 2.5 months of age had no influence on either the formation or maintenance of the conditioned reflex to the complex signal developed prior to the operation. The extirpation of the SMC in preliminarily trained kittens aged 3.5 months and older leads to disinhibition of the differential components when the positive conditioned reflex to the complex signal is maintained. In untrained kittens of the same age the extirpation of the SMC was manifested in the animals' incapacity to inhibit the motoric reaction to the differential signal. The question of the role of the SMC in ontogenesis during the formation of adequate forms of behavior which require the achievement of intersensory interactions is discussed.Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti imeni I. P. Pavlova, Vol. 39, No. 4, pp. 618–626, July–August, 1989.     

Assessment of contrast sensitivity in kittens after the critical developmental period

Spatial contrast sensitivity was measured in kittens aged 6, 9, and 12 months and in adult cats. Cats had to open one of two small windows, which had a photograph of a grid, in order to obtain food reinforcement. The nonreinforced stimulus was a photograph of a uniform field of the same mean luminance. Visual acuity was constant in kittens aged 6 to 12 months. However, six-month-old kittens had low contrast sensitivity at low spatial frequencies (<0.6 cycles/degree). At the age of nine months, contrast sensitivity over this range increased, though the level seen in adult cats was reached only at the age of 12 months. It is suggested that the increase in contrast sensitivity occurring after the critical developmental period in kittens reflects maturation of higher-order cortical fields involved in the process of recognition. Laboratory of Visual Physiology, I. P. Pavlov Institute of Physiology, 6 Makarov Bank, 199034 St. Petersburg, Russia. Translated from Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 82, No. 10-11, pp. 73–76, October–November, 1996.     

Effects of Divergent Strabismus on the Horizontal Connections of Neurons in the Cat Visual Cortex

Neuron connections of eye dominance columns in the visual cortex were studied in kittens at age 5–6 months with experimental strabismus induced on days 13–16 of life (by tenotomy of the medial ocular muscle). A photographic method was used to assess the angle between the visual axes of the eyes. The operated oculomotor muscle was found to undergo partial reattachment to the eyeball. In some kittens, the operated eye returned to the normal position, while others showed persisting deviation of the eyes by 5–15°. Loss of the binocular properties of cortical neurons have been demonstrated in such animals (Sireteanu et al., 1993). Differences were seen in the extents of connections of cortical eye dominance columns between these groups of cats. Elimination of diplopia and non-correspondence of the two retinal images in kittens of these groups is suggested to be mediated by different mechanisms: alternation of the eyes on fixation or suppression of the activity of the deviant eye.     

Effects of BT-melanin on recovery of operant conditioned reflexes in rats after ablation of the sensorimotor cortex

An increase in corticofugal plasticity was demonstrated in adult rats after unilateral ablation of the sensorimotor cortex accompanied by intramuscular administration of low concentrations of BT-melanin solution. The result was acceleration of the process of compensatory recovery in the central nervous system, this being supported by the rapid recovery of a previously acquired operant conditioned reflex and movement of the paralyzed limb as compared with control animals. It is suggested that compensation of the motor deficit arising after ablation of the sensorimotor cortex is mediated by the ability of the two major motor systems of the brain — the corticospinal and the corticorubrospinal — to exhibit mutual substitution of their functions. This phenomenon of the functional switching of descending influences also occurred in rats of the control group not exposed to BT-melanin. However, the difference between the recovery times of the operant conditioned reflex and limb movement in the control and experimental groups provided evidence of an apparent acceleration in these processes as a result of BT-melanin. These results suggest that low concentrations of BT-melanin may have applied uses. __________ Translated from Zhurnal Vysshei Nervnoi Deyatel’nosti imeni I. P. Pavlova, Vol. 56, No. 3, pp. 384–391, May–June, 2006.     

Influences of an acoustic signal with ultrasound components on the acquisition of a defensive conditioned reflex in Wistar rats

The effects of short (90 sec) exposures to a complex acoustic signal with ultrasound components on the acquisition of a defensive conditioned two-way avoidance reflex using an electric shock as the unconditioned stimulus in a shuttle box were studied in female Wistar rats. This stimulus induced audiogenic convulsions of different severities in 59% of the animals. A scale for assessing the ability of rats to acquire the conditioned two-way avoidance reflex was developed. Presentation of the complex acoustic signal was found to be a powerful stressor for Wistar rats, preventing the acquisition of the reflex in the early stages (four and six days) after presentation. This effect was independent of the presence and severity of audiogenic convulsions in the rats during presentation of the acoustic signal. On repeat training nine days after the acoustic signal (with the first session after four days), acquisition of the reflex was hindered (as compared with controls not presented with the acoustic signal). However, on repeat training at later time points (1.5 months after the complex acoustic signal, with the first session after six days), the rats rapidly achieved the learning criterion (10 correct avoidance responses in a row). On the other hand, if the acoustic signal was presented at different times (immediately or at three or 45 days) after the first training session, the animals’ ability to acquire the reflex on repeat training was not impaired at either the early or late periods after exposure to the stressor. These results suggest that the complex acoustic signal impairs short-term memory (the process of acquisition of the conditioned two-way avoidance reflex at the early post-presentation time point) but has no effect on long-term memory or consolidation of the memory trace. __________ Translated from Zhurnal Vysshei Nervnoi Deyatel’nosti imeni I. P. Pavlova, Vol. 56, No. 3, pp. 371–378, May–June, 2006.     

Influence of dilantin on the reactions of neurons of the sensorimotor cortex and hippocampus during learning

The probability of movements in response to light flashes, the conditional signal of a defense reflex, did not alter against the background of the action of dilantin (D) in a dose which, according to published data, attenuates posttetanic potentiation (PTP). A weak but stable disinhibition of the motor reaction was observed in response to flashes turned on against the background of conditional inhibition, continuous light. The activation of neurons of sensorimotor cortex in response to reinforced and nonreinforced light flashes against the background of D was intensified in the same way as was observed previously as exemplified by the reactions of neurons of the visual cortex [3], while it was diminished in response to painful reinforcement. The acceleration of impulses in response to reinforced light flashes under the influence of D became weaker in the hippocampus, by contrast with neurons of the new cortex. It can be concluded on the basis of the data obtained that PTP does not participate in the storage in the new cortex of long-term memory of the biological significance of an activating stimulus. Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Saint Petersburg. Translated from Zhurnal Vysshei Nervnoi Deyatel’nosti imeni I. P. Pavlova, Vol. 44, No. 4-5, pp. 714–720, July–October, 1994.     

Varied influence of damage to the motor cortex on precision avoidance and escape reactions in dogs

The influence of local extirpation of the representation of the forelimb in the motor area of the cortex on the performance of precision elevations of this limb was investigated. Even imprecise avoidance reactions to an acoustic signal did not recover spontaneously. Irregular motoric reactions which were insufficient in amplitude could easily be restored in the course of retraining, but precise movements (both rapid fused, as well as relatively slow stepwise movements) did not recover for at least a half year after the operation. By contrast with this, precise rapid reactions in response to electrical stimulation of a “working” limb (inducing unconditioned reflex flexion) remained essentially preserved, i.e., the capacity to stop the movement in the correct (previously learned) position of the limb was preserved. The capacity to fix the position of the raised limb was not lost, but was persistently impaired. The capacity to overcome the unconditioned reflex flexion during the performance of extensor “slow” escape reaction was reduced sharply and persistently. Limb presentation reactions regulated by vision were essentially spontaneously and nearly completely restored within a month. The study has been supported by the Russian Basic Research Fund (Project No. 93-04-6267). Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Saint Petersburg. Translated from Zhurnal Vysshei Nervnoi Deyatel’nosti imeni I. P. Pavlova, Vol. 44, No. 4-5, pp. 691–701, July–October, 1994.     

Effect of active immunization with plasma aminooxidase on mnestic processes and transmittory systems in rat brain

Immunization to bovine plasma amine oxidase improves conditioned reactions in rats. This effect is accompanied by inhibition of plasma amine oxidase and monoamine oxidase A, a decrease in the content of 5′-hydroxyindolacetic acid, and accumulation of serotonin, dopamine, and norepinephrine in neuronal mitochondria of the sensorimotor cortex and caudate nucleus. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 125, No. 7, pp. 39–42, July, 1998     

Changes in the Activity of Amyloid-Degrading Metallopeptidases Leads to Disruption of Memory in Rats

In old male Wistar rats (older than 12 months), or adult males (3–4 months) subjected to prenatal hypoxia (7% O₂, 3 h, E14), a disruption of short-term memory was observed. Prenatal hypoxia also led to a decrease in the brain cortex of the levels of expression of the metallopeptidases neprilysin (NEP) and endothelinconverting enzyme (ECE-1) which regulate some neuropeptides and are the main amyloid–beta (Αβ)-degrading enzymes. Moreover we have demonstrated a significant decrease (by 2.7 times) of NEP activity in the sensorimotor cortex of old rats and of adult rats subjected to prenatal hypoxia (by 1.7 times). To confirm possible involvement of these enzymes in memory we have performed an analysis of the effect of microinjections of phosphoramidon – an inhibitor of NEP and ECE-1, and thiorphan – an inhibitor of NEP – into the rat sensorimotor cortex. Using a two-level radial maze test, disruption of short-term memory was observed 60 and 120 min after i.c. injections of phosphoramidon (10^–2 M) and 30 and 60 min after i.c. injections of thiorphan (10^–2 M). Thus, involvement of NEP and ECE-1 in short-term memory observed in this study allows us to suggest that one of the main factors in disruption of cognitive functions after prenatal hypoxia or in the process of ageing could be a decrease in the level of expression and activity of metallopeptidases participating in metabolism of Αβ and other neuropeptides.     

Dynamics of the reactivity of cortical neurons to the repeating isolated action of L-glutamate and acetylcholine

A comparative analysis of the probability, directionality, and intensity of the changes in the average frequency of the baseline (BIA) and L-glutamate-induced (GlIA) and acetylcholine-induced (AChIA) impulse activity of individual neurons of the sensorimotor cortex of unanesthetized rats showed that the reactions to Gl are most variable; this is expressed in a significantly higher percent of neurons with potentiation of responses to Gl as compared with the proportion of cells which manifested an increase in the AChIA in the course of 20 applications of the mediators. As a result of 100 applications, the GlIA decreases most frequently; also, the degree of decrease in GiIA over the entire duration of the testing exceeds the degree of decrease in AChIA. It is more characteristic of ACh than of Gl to increase the level of BIA in the periods between the reactions to ACh, while in the case of repeated application of Gl, dynamics of decrease in BIA are characteristic. The results are discussed from the perspective of a possibly different functional role of the glutamatergic and cholinergic neuromediator systems in the cerebral cortex in the process of formation of the dynamics of neuronal activity during learning. M. V. Lomonosov Moscow State University. Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti imeni I. P. Pavlova, Vol. 44, No. 1, pp. 135–142, January–February, 1994.     

Effects of Transient and Prolonged Flashing Light Stimulation on the Cytochrome Oxidase Module System in Layer IV of the Primary Visual Cortex of Kittens

Cytochrome oxidase spots in layer IV of field 17 of the primary visual cortex were studied in kittens aged 33, 49, and 93 days, stimulated with a light flashing at a frequency of 15 Hz. The kittens of one group received stimulation from the moment of eye opening until euthanasia (prolonged stimulation); other groups received stimulation for eight days starting from ages 26, 42, or 85 days (transient stimulation), again until euthanasia. Both types of stimulation were found not to alter the geometrical characteristics of cytochrome oxidase spots, but led to significant increases in the contrast of spots located in the splenial gyrus. Increases in spot contrast in the lateral gyrus occurred only after prolonged stimulation to age 93 days or after transient stimulation from age 26 days to age 33 days. Thus, stimulation of kittens of different ages with a light flashing at a frequency of 15 Hz led to structural-metabolic changes in the primary visual cortex. These changes were apparent to different extents in areas of the cortex responsible for central and peripheral vision. This may be explained, firstly, by the predominant activation of the Y conducting channel of the visual system and, secondly, by the increase in dominance of the contralateral input to the primary visual cortex. Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 94, No. 5, pp. 557–565, May, 2008.     

Flexion reflex modulation during stepping in human spinal cord injury

The flexion reflex modulation pattern was investigated in nine people with a chronic spinal cord injury during stepping using body weight support on a treadmill and manual assistance by therapists. Body weight support was provided by an upper body harness and was adjusted for each subject to promote the best stepping pattern with the least manual assistance required by the therapists. The flexion reflex was elicited by sural nerve stimulation with a 30 ms pulse train at 1.2–2 times the tibialis anterior reflex threshold. During stepping, stimuli were randomly dispersed across the gait cycle which was divided into 16 equal bins. A long latency (>110 ms) flexion reflex was present in all subjects, while a short (>30 ms) and a medium latency (>70 ms) flexion reflex were present only in three subjects. For each response, the non-stimulated EMG was subtracted from the stimulated EMG at identical time windows and bins, normalized to the maximal corresponding EMG, and significant differences were established with a Wilcoxon rank-sum test. The long latency flexion reflex was facilitated at late stance and during the swing-to-stance transition phase. A reflex depression was present from heel strike until mid-stance and during the swing-to-stance transition phase. The short and medium latency flexion reflexes were depressed during mid-stance followed by facilitation during the stance-to-swing transition phase. Regardless of the latency, facilitatory flexion responses during the swing phase coincided with decreased activity of ipsilateral ankle extensors. The flexion reflex was modulated in a phase dependent manner, a behavior that was absent for the soleus H-reflex in most of these patients (Knikou et al. in Exp Brain Res 193:397–407, 2009). We propose that training should selectively target spinal reflex circuits in which extensor muscles and reflexes are involved in order to maximize sensorimotor recovery in these patients.     

Mechanisms of the formation of reactions of cat motor cortex neurons associated with the triggering of the conditioned placing reflex: A hypothesis

The possible physiological mechanisms of the generation of reactions by neurons of the cat motor cortex during the triggering of a conditioned placing reflex are examined. It is hypothesized that neurons of the motor cortex function as a neuronal generator similar to the spinal generator of locomotion, which can be triggered through ion channels that are controlled by NMDA-type glutamate receptors. The conditions necessary for the opening of these channels under the influence of glutamate are achieved by the conditioned “arousal reaction”, the neurochemical equivalent of which is an intensification of the cholinergic and noradrenergic and/or serotoninergic afferentation to the cortex. M. V. Lomonosov Moscow State University. Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti imeni I. P. Pavlova, Vol. 44, No. 6, pp. 963–973, November–December, 1994.     

The Possibility of Left Dominant Activation of the Sensorimotor Cortex During Lip Protrusion in Men

Lip protrusion requires bilateral symmetrical movements of the facial muscles, but the laterality of the activated sensorimotor cortex corresponding to the area of the face activated during lip protrusion remains under discussion. In this study, blood-oxygenation-level-dependent (BOLD) responses in the sensorimotor cortex during non-verbal lip protrusion were evaluated in a 3T magnetic field in twenty healthy right-handed subjects. The results showed that the activated sensorimotor area on the left side was larger than that on the right side, and there was a statistically significant difference in the number of activated voxels between the left and right sensorimotor cortex in an individual study of the male group, although approximately symmetrical motor action potentials of facial muscles were recorded during lip protrusion. There was a statistically significant difference in interaction between the hemisphere (right and left) and sex (men and women) and multiple comparison test showed statistical significant differences between “men and right” and “men and left”, and between “men and left” and “women and left”. The peak value of the percent changes in BOLD signal responses on the left side was approximately twice as high as that on the right side in the males of the group, though the bilateral sensorimotor cortex was almost equally activated in the females in the group. In addition, the left primary sensory area related to the face area was significantly activated as a region where Male was more active than Female in a general linear model (multi-study, multisubject) analysis. This study revealed the possibility that the left sensorimotor cortex was more closely involved in non-verbal mouth movement in men, suggesting sex-related differences in sensorimotor cortex activation.     

Responses to Light of Sensorimotor and Visual Cortex Neurons in Rabbits with a Cryptic Focus of Excitation (a defensive dominant) in the CNS

In the sensorimotor cortex of rabbits with a formed cryptic (subthreshold) focus of excitation in the CNS, the spike frequencies of neurons responding to light stimulation were significantly lower (p = 0.01) than the spike frequencies of neurons not responding to light. Similar findings were obtained in the visual cortex of intact rabbits. In this case too, the spike frequencies of neurons responding to stimulation were significantly lower (p = 0.01) than the spike frequencies of neurons not responding to light stimulation. In both intact rabbits and rabbits with a cryptic focus of excitation formed in the CNS, 36 % of neurons in the sensorimotor cortex responded to light stimuli not specific to this area. In the sensorimotor cortex of rabbits with a cryptic focus of excitation formed in the CNS, as compared with intact rabbits, there were significantly more (p = 0.01) cells responding to light stimuli with latent periods of less than 100 msec and significantly fewer (p = 0.02) responding to light stimuli with latencies of 200–300 msec. In the visual cortex of rabbits with a formed cryptic focus of excitation in the CNS, as compared with intact rabbits, significantly fewer (p = 0.01) neurons responded to light stimuli with latent periods of 50–100 msec.     

Spontaneous Activity and Rhythm Assimilation Reactions in Baby Rabbit Hippocampal Neurons During Learning: Age-Related Characteristics

The neural mechanisms of the age-related characteristics of memory formation were studied in experiments based on a model providing an analog of a conditioned reflex to time: trace assimilation of the rhythm with which neurons in hippocampal field CA1 were stimulated, in rabbits aged 1–4 weeks and 5–6 months. Stages of changes in neuron spike activity characteristic for developing animals were described. In animals studied one week after birth, there was a predominance of silent cells and cells with low spontaneous activity. At 2–3 weeks of life, the level of spontaneous neuron activity increased, reaching adult levels by 25–30 days. The dynamics of the ontogenetic development of learning ability showed a number of stages: from virtually complete inability to form and assimilate traces of the rhythm (at age 6–7 days) to the stage of good formation and rapid forgetting (8–14 days), and, finally, the development of complete memory (25–30 days). The synchronous development of plastic rearrangements and the level of spontaneous neuron activity provided evidence of the direct involvement of the mechanisms underlying the formation of spontaneous spike activity in the organization of neural processes supporting adaptive reactions in the developing animal. __________ Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti imeni I. P. Pavlova, Vol. 55, No. 1, pp. 52–59, January–February, 2005.     

Coherence analysis of electrical activity in the rabbit brain during the process of substitution of dominants

Coherence analysis was used to study intercenter relationships between biopotentials in the sensorimotor cortex (forelimb and blink representation areas) and the visual cortex in both hemispheres and the ventrolateral nucleus of the thalamus (VPL) of the left and right thalami during the formation of a motor defensive dominant (electrical stimulation of the limb skin) on a background of an induced (by stimulation of the cornea with an air jet) blink dominant. Characteristic electrophysiological measures of the dominant state (increases in the mean coherence level of potentials in the delta frequency range in, structures involved in the functional defensive limb reflex system), along with the absence of behavioral manifestations of the motor dominant in the blink dominant, indicated that a cryptic potential dominant focus was created in the CNS in these conditions, and that this affected ongoing animal activity. Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti imeni I. P. Pavlova, Vol. 48, No. 4, pp. 616–622, July–August, 1998.     

Visuomotor restriction of one eye in kittens reared with alternate monocular deprivation

Summary It is known that kittens reared in ways that restrict movement while visual stimulation is received exhibit deficits in visually guided behavior. Presumably, the behavioral dysfunction is due to a lack of sensorimotor coordination during visual exposure. The current investigation was undertaken to study this effect both physiologically and behaviorally. Two groups of kittens were normally reared until they were nearly 4 weeks old. They were then placed in a darkroom and exposed daily for 1–2 hours while one eye was occluded. On alternate days, alternate eyes were covered. One group was restrained in a body cast while a given eye was exposed, but the kittens were free to move about while the other eye received visual experience. A second control group was alternately occluded, but freely mobile during all exposures. An additional cat was also unrestrained during daily rearing periods and neither eye was ever occluded.Behavioral tests showed clear deficits when the passive eye of the restrained-unrestrained group was used. Deficiencies were found in visually guided paw placing, pursuit eye movements, and jumping behavior to a platform. Responses of single cells were studied in area 17 of the visual cortex. Ocular dominance distributions showed marked reductions in binocularity for alternate occluder cats. The eye that had received exposure while animals were active in the restrained-unrestrained group also tended to predominate but the difference was not statistically significant.     

Genetic models of impaired prestimulus inhibition of the shudder reaction

Prestimulus inhibition of the fear reaction (weakening of reflex shudder when the standard sound stimulus is preceded by a weak sound) was studied in eleven inbred mouse strains. Inhibition is regarded as a selective suppression of sensorimotor reactions typical of schizophrenia. Considerable genotype-related, differences were revealed in this inhibition. The reaction was not observed in DBA/2 mice and was weak (31%) in PT mice. Inhibition, of the shudder reflex was practically the same (54.8%) in mice with abnormal behavior: C57B1 (high inclination to alcohol) and CBA (predisposition to catalepsy). There was no correlation between reflex shudder and prestimulus inhibition. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 126, No. 7, pp. 86–89, July, 1998