Corticohypothalamic relationships during the development and realization of the conditioned reflex

The influence of motivational, emotiogenically positive and emotiogenically negative structures of the hypothalamus on the development and realization of conditioned reflexes was investigated in the experiments on dogs, cats, and rats. It was shown that the motivational structures primarily increase excitability of cortical neurons during the development of the conditioned connection, while the emotiogenically negative and emotiogenically positive structures increase the efficiency of synapses. A high degree of correlatedness of the averaged evoked responses to the conditional stimulus in the hypothalamus and new cortex is characteristic for the consolidated conditioned reflex. Direct stimulation of the motivational-alimentary zones of the hypothalamus reproduce food-procuring conditioned reflexes in dogs, while stimulations of the emotiogenically negative zones reproduce defense conditioned reflexes. Stimulation of the emotiogenically positive zones does not reproduce either; however, an intensification of the activity of neurons of the hypothalamus was recorded in rats during the successful accomplishment of the conditioned reaction of avoidance of an aversive stimulus. In cats which are capable of restraining a conditioned motoric reaction for the sake of obtaining a preferred food, the “motivational”, long-latency functional connections between neurons of the lateral hypothalamus and the prefrontal cortex predominate. Short-latency “informational” connections predominate in the “impulsive” cats. Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti imeni I. P. Pavlova, Vol. 43, No. 2, pp. 12–21, March–April, 1993.     

Appearance of functional connections between neurons resulting from changes in the frequency of their spike activity during the performance by animals of conditioned-reflex food-procuring responses

Cats were conditioned to a food-procuring reflex to time. Correlation analysis was applied to multineuron activity in the motor cortex to study the functional connections between neurons with changing and constant instantaneous spike frequencies on performance by the animals of the passive waiting phase of the conditioned reflex, the number of functional connections between “areactive” neurons was smaller than that between “reactive” neurons; during the phase of active waiting, the numbers of functional connections became similar. The increase in the number of functional connections between “areactive” neurons during the active waiting phase appears to reflect an intensification of the analysis and processing of information, while changes in the functional connections between “reactive” neurons was regarded as allowing the possibility of correcting functional structures in the case of a rapid change in the situation or state of the animal. Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow. Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti, Vol. 45, No. 6, pp. 1134–1142 November–December, 1995.     

Effect of stimulation of the lateral hypothalamus on the correlation of neuron spike activity in the rabbit neocortex

Cross-correlation and autocorrelation histograms were constructed with the aim of studying correlated spike activity of neurons in the visual and sensorimotor regions of both hemispheres of the rabbit brain before and after stimulation of the right and left lateral hypothalamic regions, which generates food-motivated responses. Stimulation of the left hypothalamus produced larger rearrangements in correlated neuron firing than stimulation of the right hypothalamus. Stimulation of the left hypothalamus, unlike that of the right hypothalamus, was followed by significant increases in the numbers of pairs of left hemisphere neocortical neurons with linked activity, and also induced the sequential firing of neurons in a particular defined order: sensorimotor cortex cells fired first, followed by visual cortex neurons after delays of up to 120 msec. It is concluded that cortical interhemisphere asymmetry in conditions of hunger is associated with nonuniform functioning of the right and left lateral hypothalamic regions. Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow. Translated from Fiziologicheskii Zhurnal Vysshei Nervnoi Deyatel'nosti, Vol. 46, No. 6, pp. 1068–1075, November–December, 1996.     

Suppression of synaptic input of defense behavior command neurons by stimulation of neurons of the mesocerebrum in a preparation of the isolated CNS of the common snail

The intestinal nerve was stimulated in combination and uncombined with extracellular stimulation of the mesocerebral region of the brain, as well as with stimulation of serotoninergic neurons, in experiments on a preparation of the isolated CNS of the common snail, with preservation of the nerve connections with the sexual system. Reponses were recorded in command neurons of defense behavior. The data were obtained indicating that, in the case of combinations with extracellular stimulation of the mesocerebrum, an analog of a conditioned reaction of diminution of EPSP in the command neurons of the serotoninergic neurons, sensitization appears, both in the case of combined and uncombined presentation of the stimuli. This study was supported by the Russian Basic Research Fund (project No. 94-04-122090). Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow. Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti imeni I. P. Pavlova, Vol. 45, No. 1, pp. 163–170, January–February, 1995.     

Influence of dilantin on the reactions of neurons of the visual cortex and the behavior of rabbits during learning

Changes in behavior in response to light flashes, the conditional stimulus of a defense reflex, were not observed following the administration of dilantin, a preparation which attenuates posttetanic potentiation, in rabbits with preliminarily developed defense and inhibitory conditioned reflexes; weak disinhibition of movements appeared in response to the action of flashes against the background of a conditional inhibitor. The similarity of the reactions of the neurons of the visual cortex to light flashes, the CS, with the responses to their joint action with the reinforcement, did not weaken in the majority of instances, while in several neurons, it intensified. The differences in the responses to reinforced and inhibitory light flashes did not disappear following the administration of dilantin, but they attenuated in some of the neurons due to filling of the inhibitory pause with impulses. The results obtained make it possible to draw the conclusion that posttetanic potentiation does not participate in the maintenance of developed conditioned reflexes. Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow. Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti imeni I. P. Pavlova, Vol. 44, No. 1, pp. 48–56, January–February, 1994.     

Long-term potentiation of the late NMDA-dependent components of neuron responses in the cat motor cortex to stimulation of the direct cortical input from field 5 of the parietal cortex

Bicuculline-filled microelectrodes were used to record responses to weak stimulation of the parietal cortex in field 5 of the motor cortex of anesthetized cats, and revealed late excitatory responses of neurons similar to those seen in the motor cortex of conscious cats in response to conditioned stimulation of the parietal cortex triggering a conditioned reflex consisting of placing the paw on a support. Tetanic stimulation of the parietal cortex (10–20 sec, 100 Hz) in the same conditions evoked long-term potentiation of late responses, resulting in the formation and enhancement of responses, along with decreases in the latent period of responses. Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti, Vol. 49, No. 2, pp. 279–286, March–April, 1999.     

Creation of a defense dominant during the functioning of a blink dominant in the rabbit

The possibility of creating (through serial electrodermal stimulation of the limb) a defense dominant during the formation and functioning of a blink dominant was investigated in chronic experiments in rabbits. The formation of a motor dominant against the background of a blink dominant was difficult. Sequential, but not simultaneous, manifestation of the dominants under investigation was observed when the motor defense dominant was created against the background of a formed blink dominant. Difficulty in the formation of the motor dominant was also observed in the presence of transition to an inhibitory state, as a result of the repeated summation of the initial dominant focus, created via the reflex route, and in the presence of induction activation of a secondary dominant focus in symmetrical structures. Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow. Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti imeni I. P. Pavlova, Vol. 45, No. 3, pp. 464–471, April–May–June, 1995.     

Assessment of brightness and color differences by neurons in the superior colliculus of the rabbit

The responses of 83 neurons in the rabbit superior colliculus to substitution of color stimuli of different brightnesses and black-and-white stimuli of different intensities were studied. Superior colliculus neurons were found to respond with initial and late phasic discharges (over the periods 50–90 msec and 120–300 msec from the moment of stimulus substitution respectively), along with prolonged tonic discharges whose spike frequencies depended on the intensity of the stimulus. Analysis of the phasic responses of the neurons allowed three groups of cells to be identified. One group of cells (25 of the cells studied, 30%), identified on the basis of early neuron responses, were specialized for detecting brightness differences between black-and-white and color stimuli of different intensities. The sensory spaces reconstructed on the basis of spike discharge frequencies in the early discharges of these neurons were achromatic and two-dimensional. Another group of neurons (16 of the cells studied, 19%) were mainly identified on analysis of late phasic discharges and had four-dimensional spaces with two color and two achromatic axes. The third group of cells (four neurons, 5%) had early discharges with two-dimensional achromatic sensory spaces and late discharges with four-dimensional spaces. It is suggested that reconstruction of the four-dimensional space requires processing of information from the visual cortex on color and intensity differences between stimuli. The sensory spaces of superior colliculus neurons reconstructed on the basis of phasic discharges essentially coincided with the sensory spaces of neurons in the visual cortex and lateral geniculate body and spaces obtained by analysis of the N85 component of visual evoked potentials in rabbits recorded using similar stimulation. This may support the vector coding principle in the visual analyzer. __________ Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti imeni I. P. Pavlova, Vol. 57, No. 5, pp. 576–590, September–October, 2007.     

Computation of Color and Brightness Differences by Rabbit Visual Cortex Neurons

Extracellular recording of the activity of 54 neurons in the rabbit visual cortex in responses to substitutions of eight colored and eight monochromatic stimuli in pairs was studied. Stimuli were uniform flashes of light displayed on an SVGA monitor and illuminated the whole retina. The responses of phasic neurons showed an initial discharge (50–90 msec from the moment of the change in stimulus), associated with the brightness or color difference between the stimuli. These “discrimination discharges” were used to construct an 8 × 8 matrix for each neuron, showing the mean number of spikes per sec in responses to changes in different pairs of stimuli. Processing of the matrix by factor analysis identified the major factors determining the axes of the sensory space. A brightness space with only two dimensions, with darkness and brightness orthogonal axes, was seen for 30% of neurons. A four-dimensional color space was seen in 22% of neurons, with two color and two achromatic axes. The sensory space of these neurons was similar to the spaces obtained by analyzing the early components of visual evoked potentials in rabbits induced by changes in color stimuli and behavioral operant responses in conditioned reflex color differentiation. The fundamental coincidence of the sensory spaces obtained by different methods identifies the general nature of the principle of vector coding and the existence of special neuronal mechanisms for detection of color and brightness differences in the visual field. __________ Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti imeni I. P. Pavlova, Vol. 55, No. 1, pp 60–70, January–February, 2005.     

Interactions between homogeneous conditioned motor reflexes during conditioned reflex switching: Transfer of learning and interference

Studies in rabbits of the time course of the formation of conditioned reflex switching of homogeneous reflexes showed that learning involved three main stages, characterized by the extent of stability of the conditioned reflexes, their interaction, and the level of switching. Formation of conditioned reflex switching was found to involve transfer of motor learning and interference of motor reflexes. M. V. Lomonosov Moscow State University. Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti, Vol. 45, No. 6, pp. 1112–1120, November–December, 1995.     

Real-time distribution of linked spike activity in cortical neurons during learning in the cat

Analysis of the distribution of linked spike activity showed changes occurring within the structure of interneuron functional connections during learning. In an electric shock defensive reflex, concentration of linked spikes from cat motor cortex neurons was observed on signal presentation, while in a conditioned food-procuring reflex to time, this was confined to the moment at which reinforcement was provided. This can be regarded as the appearance of a reflex at the level of interneuron interactions. This conclusion is supported by the observation that in well-trained animals, concentration of linked spikes could be seen at the place of the conditioned reflex response, even in the absence of defensive and food-procuring movements. Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow. Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti, Vol. 46, No. 2, pp. 291–300, March–April, 1996.     

Temporospatial organization of membrane-synaptic modifications and topograms of slow oscillations in cortical potentials during learning

This report concerns the important question of the specificity of the organization of the different stages of formation of a conditioned reflex, considered at the level of membrane-synaptic modifications, which are compared with changes in the spatial organization of slow cortical potentials. A defined sequence of involvement of cellular mechanisms is demonstrated during learning, which may be responsible for various features of the spatial organization of slow cortical potentials. Changes in cellular excitability in cortical neurons are probably connected with oscillations in the overall level of instantaneous topograms and, thus, with the general level of spatial synchronization; the involvement of excitatory and inhibitory synaptic connections (with efficiencies corresponding to different stages in the reflex) may determine the formation of the relief seen in topograms. Parameters at both levels depend on the effects of the hypothalamus on the cortex. Data included in this paper were presented at the “Physiological and Biochemical and Biochemical Bases of Brain Activity” Symposium, St. Petersburg, June 22–24, 1994. Institute of Higher Nervous Activity and Neurophysiology. Russian Academy of Sciences, Moscow. Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti, Vol. 45, No. 6, pp. 1121–1133, November–December, 1995.     

Lock-and-key mechanisms of cerebellar memory recall based on rebound currents

A basic question for theories of learning and memory is whether neuronal plasticity suffices to guide proper memory recall. Alternatively, information processing that is additional to readout of stored memories might occur during recall. We formulate a "lock-and-key" hypothesis regarding cerebellum-dependent motor memory in which successful learning shapes neural activity to match a temporal filter that prevents expression of stored but inappropriate motor responses. Thus, neuronal plasticity by itself is necessary but not sufficient to modify motor behavior. We explored this idea through computational studies of two cerebellar behaviors and examined whether deep cerebellar and vestibular nuclei neurons can filter signals from Purkinje cells that would otherwise drive inappropriate motor responses. In eyeblink conditioning, reflex acquisition requires the conditioned stimulus (CS) to precede the unconditioned stimulus (US) by >100 ms. In our biophysical models of cerebellar nuclei neurons this requirement arises through the phenomenon of postinhibitory rebound depolarization and matches longstanding behavioral data on conditioned reflex timing and reliability. Although CS–US intervals <100 ms may induce Purkinje cell plasticity, cerebellar nuclei neurons drive conditioned responses only if the CS–US training interval was >100 ms. This bound reflects the minimum time for deinactivation of rebound currents such as T-type Ca²⁺. In vestibulo-ocular reflex adaptation, hyperpolarization-activated currents in vestibular nuclei neurons may underlie analogous dependence of adaptation magnitude on the timing of visual and vestibular stimuli. Thus, the proposed lock-and-key mechanisms link channel kinetics to recall performance and yield specific predictions of how perturbations to rebound depolarization affect motor expression.     

Interactions of rabbit neocortical neurons during natural food motivation

Studies were carried out on the interaction between neurons in the visual and sensorimotor, and in the visual and frontal regions of the neocortex of both hemispheres in sated and starved rabbits. In starved rabbits, there was an increase in number of pairs of neurons with correlated activity, along with an increase in the number of pairs of neurons with frequency interactions in the theta range and a reduction in the number of pairs with interactions in the alpha range; interhemisphere asymmetry occurred in the interaction of neurons in the visual and sensorimotor regions. The greatest increase in the number of pairs of neurons with correlating activity was seen in the left hemisphere, and a preferential sequence of neuron firing appeared. Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow. Translated from Z Zhurnal Vysshei Nervoii Deyatel'nosti, Vol. 46, No. 1, pp. 108–116, January–February, 1996.     

Linked Spike Activity of Rabbit Neocortex Neurons during Self-Stimulation of the Lateral Hypothalamus

Cross-correlation and autocorrelation histograms were constructed to study the linkage between the spike activity of neurons in the visual and sensorimotor areas of both cerebral hemispheres in rabbits over periods of 10 sec after self-stimulation of the right and left lateral hypothalamus. Self-stimulation was followed by an increase in the number of pairs of cells in which neurons in the sensorimotor area fired after cells in the visual cortex (from 24 ± 6% to 44 ± 6%). Analysis of the spectrum of linked discharges revealed increases in the alpha and theta frequency ranges; the main increases in the right hemisphere were in the alpha range, while the main increases in the left hemisphere were in the theta range. Interhemisphere asymmetry in the interaction of cortical neurons was not associated with the side of the hypothalamus subjected to stimulation.     

Similarity of the effects of training and application of serotonin on the electrical activity of live hippocampal slices from rats

A pronounced sensitization phase was observed on low-frequency stimulation of hippocampus slices from rats decapitated immediately after training to a conditioned bilateral escape reflex. The same effect was recorded in slices from control animals after brief application of serotonin. Serotonin had a significantly smaller effect on the electrical activity of trained animals. Changes in the efficiency of the serotoninergic input to hippocampus neurons are suggested as one of the factors eliciting low-frequency facilitation in trained rats. Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow. Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti, Vol. 46, No. 1, pp. 93–99, January–February, 1996.     

Computation of color and brightness differences by neurons in the lateral geniculate nucleus of the rabbit

The responses of 51 neurons in the lateral geniculate nucleus of the rabbit to substitution of colored stimuli different brightness and stimuli differing only in intensity were studied. Neurons in the geniculate nucleus, like neurons in the visual cortex, were found to respond with initial phasic discharges at 50–90 msec after stimulus substitution, the magnitudes of these responses correlating with the interstimulus differences; neurons also showed prolonged tonic responses in which the spike frequency depended on the intensity of the stimulus presented. Analysis of phasic responses allowed two groups of neurons to be identified: some were specialized to discriminate stimulus intensity only, while others were specialized to discriminate both the intensity and the color tone of the stimulus. Use of the magnitude of the early phasic discharge as a measure of the difference between stimuli yielded a sensory space for lateral geniculate nucleus neurons. The responses of neurons in the first group (44 cells, 86%) produced a two-dimensional achromatic space with two axes-brightness and darkness; this structure appeared independently of whether stimuli were of the same or different color tones. The phasic responses of neurons in the second group (seven of 51, 14%) generated a four-dimensional space with two color and two achromatic axes. The color and achromatic spaces of lateral geniculate nucleus neurons were analogous to the spaces previously identified for neurons in the rabbit visual cortex using the same stimulation conditions. The sensory spaces reconstructed on the basis of neuron phasic discharges essentially coincided with the spaces obtained from analysis of the N85 component of visual evoked potentials in rabbits, which provides support for the vector information coding principle in the visual analyzer. The tonic discharges of most lateral geniculate nucleus neurons correlated linearly with changes in stimulus intensity and can be regarded as reflecting a pre-detector function for the visual cortex detector neurons. __________ Translated from Zhurnal Vysshei Nervnoi Deyatel’nosti imeni I. P. Pavlova, Vol. 56, No. 1, pp. 75–85, January–February, 2006.     

The facilitatory and depressive effects of iontophoretically applied acetylcholine on different components of neuron responses in the motor cortex of the cat during performance of a conditioned paw positioning reflex

Iontophoretic application of acetylcholine to neurons in the motor cortex of cats during performance of a conditioned reflex consisting of placing the paw on a support increased neuron excitability and facilitated “extrinsic” connections, resulting in increases in primary responses to electrical stimulation of the parietal region of the cortex, and which was independent of the first effect of suppression, which was seen only in relation to the long-latency components of the response. The functional significance of the differently directed effects of acetylcholine application is indicated by the statistically significant changes in motor reaction times seen in some experiments, which were in the same direction as changes in neuronal responses in the same experiments. Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti, Vol. 48, No. 1, pp. 99–112, January–February, 1998.     

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.     

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.