Activity of Neurons in the Pedunculopontine Nucleus during a Food-Related Operant Conditioned Reflex

The activity of 91 neurons in the compact and diffuse zones of the pedunculopontine nucleus of freely mobile rabbits was studied during performance of a food-related operant conditioned reflex. A total of 37.4% of the neurons recorded showed reactivity to the conditioned stimulus, which is evidence that the pedunculopontine nucleus is involved in operant learning. A significant predominance of excitatory responses to the conditioned stimulus and to food reinforcement was demonstrated. The main patterns of cell responses were identified, these reflecting the nature of the effect of the conditioned stimulus on neuron activity, the structure of the behavioral act, and the properties of the reinforcement, and demonstrating a relationship between the pedunculopontine nucleus and the processes of attention, motor learning, and reinforcement. Differences were seen in the associative reactive properties of the compact and diffuse zones of the pedunculopontine nucleus to the conditioned stimulus and reinforcement, which is evidence for the functional diversity of this formation and suggests a leading role for the cholinergic compact zone in food-related operant learning and reinforcement, the diffuse zone having a leading role in food-related classical conditioned-reflex learning.     

Possible Mechanisms of the Involvement of Dopaminergic Cells and Cholinergic Interneurons in the Striatum in the Conditioned-Reflex Selection of Motor Activity

A possible mechanism for the involvement of cholinergic interneurons in the striatum and dopaminergic cells in the substantia nigra in the selection from among several types of motor activity during learning is proposed. Selection is triggered by simultaneous increases in the activity of dopaminergic neurons and a pause in the activity of cholinergic interneurons in response to the conditioned signal. The appearance of the pause may facilitate activation of GABAergic interneurons in the striatum and the action of dopamine on D2 receptors on cholinergic interneurons. Differently directed changes in dopamine and acetylcholine levels synergistically modulate the efficiency of corticostriatal inputs, such that the rules for modulation of the “strong” and “weak” inputs are opposite in sign. The subsequent reorganization of neuron activity in the cortex-basal ganglia-thalamus-cortex circuit leads to increased activity in those cortical neurons providing “strong” innervation to the striatum with simultaneous decreases in the activity of neurons providing “weak” innervation to the striatum, which may underlie the selection of the movement reaction, in which the neocortex is involved. It follows from this model that if the delay between the conditioned and unconditioned stimuli is not longer than the latent period of the reactions of dopaminergic and cholinergic cells (about 100 msec), selection of movement activity in response to the conditioned signal and learning is hindered. __________ Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti imeni I. P. Pavlova, Vol. 54, No. 6, pp. 734–749, November–December, 2004.     

Functional Asymmetry of the Frontal Cortex and Lateral Hypothalamus of Cats During an Operant Food-Related Conditioned Reflex

The extent of correlation and the latency of evoked potentials to sound, recorded bilaterally in the frontal cortex and lateral hypothalamus of cats, were studied at different stages of the acquisition of an operant food-related reflex and during sudden transfer to 30% food reinforcement. High correlation coefficients between the evoked responses of the cortex and hypothalamus with left-sided dominance were seen in conditions of high levels of food motivation at the beginning of each experiment and in conditions of the high-probability appearance of the acquired conditioned reflex throughout the rest of the experiment. Comparison of the peak latencies of the early positive (P55-80) components of evoked potentials on the right and left sides showed that shorter latent periods were seen in the cortex on the left side at all behavioral stages, while this occurred (on the left side) in the hypothalamus only when the conditioned reflex was unfixed, while after fixation of the reflex and provision of 30% reinforcement, shorter latent periods were seen on the right side. It is concluded that the high level of left-sided correlation of evoked potentials in the hypothalamus was associated with the motivational and motor components of purposive behavior and was not associated with the emotional tension of the animals provoked by the disruption of the food reinforcement stereotype.     

Reflection of the Spatial Characteristics of an Acoustic Signal in the Activity of Caudate Nucleus Neurons

Studies were performed on five dogs. Chronic experimental conditions were used to study the responses of individual neurons in the caudate nucleus to the spatial characteristics of an acoustic signal. The results showed that 92% of sound stimulus-responsive neurons in the head of the caudate nucleus in dogs generated asymmetrical responses to contra- and ipsilateral monaural stimulation, with contralateral stimulation being more effective. In 50% of caudate nucleus neurons, simultaneous stimulation of both sound inputs was more effective than contralateral stimulation. A total of 77% of sound-responsive caudate neurons demonstrated sensitivity to changes in the magnitude and sign of the interaural delay.     

Dopaminergic Modulation of Spike Activity in Sensorimotor Cortex Neurons in a Conditioned Reflex

Changes in the spike conditioned reflex reactions of sensorimotor cortex neurons during microion-tophoretic application of agonists and antagonists of glutamatergic and GABAergic transmission and their modulation by dopamine were studied. A paradoxical reaction is described, consisting of facilitation of spike responses evoked by antagonists of ionotropic glutamate transmission, which was blocked by GABA. This is evidence for the active involvement of inhibition in organizing the excitatory responses of neurons in the conditioned reflex. Application of the metabotropic glutamate transmission antagonist MCPG was accompanied by sharp suppression of the baseline and evoked activity of cortical neurons, along with increases in the latency of spike responses and conditioned reflex movement. Dopamine was found to reverse the effect of blocking metabotropic glutamate receptors and to normalize neuron activity, which is evidence for the stabilizing role of dopamine in the functioning of neocortical neurons.Translated from Zhurnal Vysshei Nervnoi Deyatel’nosti, Vol. 54, No. 4, pp. 495–507, July–August, 2004.     

Postvibration Changes in the Spike Activity of Neurons in the Medial Vestibular Nucleus

Changes in the baseline spike activity in the medial vestibular nucleus were studied after exposure to vibration for 5, 10, and 15 days. Studies addressed the distributions of neurons within this structure in terms of the regularity of their spike activity, the dynamics of neural flows, and the modalities of interspike histogram modalities. Mean values were calculated for the major statistical measures of baseline spike activity. Statistically significant changes in the major characteristics of neuron activity were seen in the medial vestibular nucleus at different periods of vibration exposure. Vibration was found to induce complex dynamic rearrangements in the baseline activity of neurons in this structure. The characteristics and functional significance of the results are discussed.     

Comparison of the Postural and Movement Components during Learning by Dogs of an Operant Defensive Reflex

Chronic experiments on six dogs using a model of an operant defensive reflex associated with maintenance of flexion of the hindlimb of specified amplitude were performed to compare the characteristics of the postural and movement components during the learning process. Dogs were placed standing on four tension platforms. Signals were activated and data were recorded and stored using original PC programs. Original programs running on another PC were used to analyze the data. All dogs showed a series of characteristics for the appearance of a diagonal pattern of conditioned reflex posture rearrangement. During the period of complete formation of the coordinated program of the operant reflex (indicated by high performance criteria for execution of the operant task), the diagonal pattern of posture rearrangement was seen extremely rarely, in only occasional performances in calm dogs. It was only during the period of complete automatization of the movement habit that the diagonal pattern of postural rearrangement was seen consistently in all performances. By this time, there was a sharp increase in the tensogram amplitudes for all four limbs, which sharp increases in the correlation coefficients between individual tensogram performances. These results suggest that in the experimental conditions used here, the diagonal pattern of postural rearrangement appeared significantly later than the movement pattern needed for resolving the operant task. These data also lead to the conclusion that dogs can complete operant defensive limb movements associated with maintaining a specified flexor posture in the absence of preliminary rearrangement of the posture having the diagonal pattern.     

The Responses of Vasopressin- and Tyrosine Hydroxylase-Expressing Neurons of the Supraoptic Nucleus in Rats to Chronic Osmotic Stimulation

The dynamics of intracellular contents of vasopressin and tyrosine hydroxylase in neuron bodies were studied in the supraoptic nucleus and the distant segments of their axons in the posterior lobe of the hypophysis in rats in conditions of salt loading lasting one, two, and three weeks. The number of vasopressin–immunoreactive neurons increased by the end of the second week of osmotic stimulation, due to the onset of vasopressin synthesis in neurons not synthesizing this hormone in normal physiological conditions. The vasopressin concentration decreased in cell bodies and axons during the first two weeks of salt loading, apparently because vasopressin release occurred at a greater level than vasopressin synthesis. During the third week, the intracellular vasopressin content remained essentially constant, demonstrating the establishment of dynamic equilibrium between the synthesis and release of the hormone. The number of tyrosine hydroxylase–immunoreactive neurons and the levels of tyrosine hydroxylase in neuron bodies and axons, at least in the largest swellings (Herring bodies), gradually increased, demonstrating that the rate of tyrosine hydroxylase was greater than its rate of enzymatic degradation. Thus, chronic stimulation of vasopressin neurons was accompanied by a series of adaptive reactions, the most important of which appears to be the expression of vasopressin and tyrosine hydroxylase synthesis by neurons which do not normally synthesize these compounds.     

Studies of the Topography of c-Fos-Expressing Neurons in the Mouse Neocortex During Training to Conditioned Reflex Freezing

Neuroscience and Behavioral Physiology -     

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.     

The Role of the Ventrolateral Nucleus of the Thalamus in the Switching of Descending Influences to Motor Activity in the Rat

Studies on rats showed that the facilitating influence of preliminary transection of the rubrospinal tract on recovery of motor activity and operant reflexes disrupted by lesioning of the red nucleus was more apparent when lesioning was chemical than when lesioning was electrolytic. This is due to the survival of cerebellothalamic fibers to the ventrolateral nucleus of the thalamus after chemical lesioning of the red nucleus with quinolinic acid. It was also shown that preliminary lesioning of the ventrolateral thalamic nucleus strongly hindered the switching of motor activity under the control of the corticospinal tract in rats subjected to section of the rubrospinal tract and lesioning of the red nucleus.     

Sequential Rearrangements of the Ensemble Activity of Putamen Neurons in the Monkey Brain as a Correlate of Continuous Behavior

Simultaneous recordings were made of the spike activity of groups of 6-7 neurons in the putamen in two monkeys (Macaca nemestrina and Macaca mulatta) during performance of alternative spatial selection. Discriminant analysis was used to evaluate the magnitude of rearrangements in spike activity in groups of neurons during transitions from each step of the behavioral program to the next, along with the degree of differences in reactivity mosaics formed at each step in different versions of task execution. Rearrangements in spike activity were noted at all steps of the program. The dynamics of rearrangements on selection of the right and left feeders were different, leading to the appearance of significant differences in the reactivity mosaics at the decision-taking and reinforcement-receiving steps. The rearrangements preceding voluntary movement of one hand were more marked in the contralateral hemisphere. During performance of movements, the volume of rearrangements could increase, though differences in rearrangements accompanying movements of the right and left hands decreased. On receipt of reinforcement, rearrangements were greater when the animals selected a specified feeder (the left feeder) independently of which hemisphere was recorded.     

Baseline Spike Activity of Neurons in the Locus Coeruleus of the Rat after Lesions to a Number of Medulla Oblongata Nuclei

Bilateral lesioning of the presublingual nucleus (nucleus praepositus hypoglossi) of the medulla oblongata induced significant changes in the nature of baseline spine activity in the locus coeruleus. After lesioning, the mean frequency of spike activity of locus coeruleus neurons decreased more than two-fold. The numbers of neurons with train-grouped activity and polymodal neurons increased significantly. Exclusion of the solitary tract nucleus led to an increase in the number of neurons with regular activity and some decrease in the mean discharge frequency in locus coeruleus neurons. These data support the suggestion that the presublingual nucleus plays a significant role in the transmission of afferent influences on the activity of locus coeruleus neurons.     

胰腺内分泌A细胞与胆碱能神经关系的探讨——迷走神经背核VAChT免疫组化研究

目的　探讨胰腺内分泌A细胞与胆碱能神经的关系。方法　选用硝酸钴选择性破坏大鼠胰腺A细胞 ,并用特异性较强的VAChT抗血清 ,从形态学上观察模型大鼠胆碱能神经在延脑迷走神经背核的变化。结果　模型大鼠VAChT免疫反应明显减弱。结论　内源性乙酰胆碱的变化与胰腺A细胞损伤有关 ,提示胆碱能神经除受其上级中枢调节外 ,还受某些内分泌细胞的影响     

Natural activation of caspase-3 is required for the development of operant behavior in postnatal ontogenesis

We have previously demonstrated transient increases in caspase-3 activity in the hippocampus of rat pups from age 17 days. We report here our studies on the effects of inhibition of caspase-3 during this period on the acquisition of a two-way avoidance reaction. Rat pups received intracerebroventricular doses of the caspase-3 inhibitor Z-DEVD-FMK On postnatal day 18. Control animals of the same age received the inactive peptide Z-FA-FMK or isotonic saline solution. Inhibition of caspase-3 during the period of its natural activation in the hippocampus during early ontogenesis was found to impair the development of operant behavior in rats. This was apparent as a reduction in the efficiency of learning during acquisition of active avoidance reactions and decreases in the numbers of intersignal reactions. Administration of the inhibitor had no specific action on the types of conditioned reflex activity less associated with operant learning. Thus, there were no differences between the experimental and control groups in the numbers of emotional reactions to the conditioned stimulus. The number of orientational-investigative conditioned reactions also showed no change after administration of Z-DEVD-FMK. On the background of the reduction in the efficiency of the acquisition of the conditioned active avoidance reflex, the number of incomplete acts, in contrast to other types of conditioned reactions, increased significantly after administration of Z-DEVD-FMK, which is evidence for the persistence of the ability to form associative connections between activation of the conditioned signal and the need to move to the other sector. The difficulty in these animals arose at the decision-taking stage on choosing the appropriate form of behavior. Changes in orientational-investigative behavior were not associated with inhibition of caspase-3 during the critical period of development, as the effects of Z-DEVD-FMK and Z-FA-FMK were similar. Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti imeni I. P. Pavlova, Vol. 57, No. 6, pp. 702–711, November–December, 2007.     

A cytoarchitectonic and histochemical study of nucleus basalis and associated cell groups in the normal human brain

Several recent studies have reported loss of neurons in the nucleus basalis in Alzheimer's disease. However, few detailed studies of the normal distribution of these neurons in the human brain have appeared. We have used Nissl staining and acetylcholinesterase histochemical staining of the human basal forebrain, alone or in combination to identify the organization of the nucleus basalis and associated cell groups, (or collectively, the magnocellular basal nucleus) in the normal human brain. The magnocellular basal nucleus includes a series of clusters of neurons and scattered perikarya extending from the medial septum and diagonal band nucleus rostrally, through the substantia innominata to the furthest caudal extent of the globus pallidus. This distribution is similar to that which has been described in the monkey. Furthermore, acetylcholinesterase-positive fibers in the human brain are seen in the two major pathways that have been identified as carrying magnocellular basal nucleus axons to the cerebral cortex in other species.These observations suggest that the topographic organization of the magnocellular basal projection to cerebral cortex in other species probably exists in man as well. It will therefore be important in future studies of the fate of these neurons in neurological degenerative diseases to assess the loss of neurons in the different components of the magnocellular basal nucleus in relation to the clinical evidence for dysfunction in the cortical areas which they innervate.     

加压素在自发性高血压大鼠与正常大鼠下丘脑视上核、室旁核神经元内表达

目的观察加压素(AVP)在自发性高血压大鼠(SHR)与正常大鼠下丘脑视上核(SON)、室旁核(PVN)内的分布。方法应用光镜和免疫细胞化学技术。结果SHR的AVP阳性细胞内分泌颗粒密集呈棕黄色,正常大鼠组则染色较浅。SHR大鼠SON内AVP阳性神经元百分数(69.30±18.10%)明显多于正常大鼠(59.53±16.97%,P<0.05),而两组大鼠PVN内AVP的表达无明显差异。结论AVP在下丘脑的血压调节活动中起着重要的介导作用,中枢AVP含量的异常增加可能与高血压的发病有关。     

The Role of the Septal Nuclei in Controlling the Activity of Vagosensitive Neurons in the Solitary Tract Nucleus in Cats

Studies on cats anesthetized with a mixture of Nembutal and chloralose were performed to study the descending influences of single, paired, and frequent stimulation of the lateral septal nucleus (LSN) and bed nucleus of the stria terminalis (BNST) on the activity of viscerosensory neurons in the solitary tract nucleus, identified by stimulation of the cervical part of the vagus nerve. Of 70 units recorded in the solitary tract nucleus, 50 were identified as primary and secondary input vagus neurons. Single stimuli applied to the septal nuclei induced initial excitation in 30% (15 units) of vagus neurons. The latent period of these responses was 5-25 msec. Presentation of paired stimuli showed that loss of the ability to respond to the second stimulus occurred at interstimulus intervals of 10-200 and sometimes 300 msec. A total of 34% (17 units) of solitary tract nucleus neurons showed tonic changes in spontaneous activity in response to rhythmic stimulation. Increasing the stimulation frequency to 10-20 Hz led to very different changes in the spontaneous rhythm, i.e., wave-like changes (decreases and increases in frequency, secondary suppression) or complete inhibition, sometimes lasting up to 10 sec after stimulation ended. A small number of units (five) showed a blocking effect of septal discharges on the visceral afferent input in conditions of paired stimulation. These results lead to the conclusion that the LSN and BNST are involved in modulating the activity of bulbar viscerosensory neurons, though their influences are mediated mainly via oligo- and polysynaptic pathways via other limbic structures (hypothalamus, amygdala).     

Dynamics of Neuron Spike Activity in the Oral Nucleus of the Pons During the Sleep-Waking Cycle in Cats

Chronic experiments on five cats were performed to study the spike activity of neurons in the oral nucleus of the pons during waking, slow-wave sleep, and paradoxical sleep. Groups of neurons with different dynamics of spike frequency were identified. Cells with rare discharges during waking and slow-wave sleep and maximum spike frequencies in the phasic stage of paradoxical sleep were regarded as PS-on neurons. Cells discharging at maximum frequency during waking, with decreases in frequency during slow-wave sleep and further decreases in paradoxical sleep, were regarded as PS-off neurons. Cells showing decreases in discharge frequency on the transition from waking to slow-wave sleep and increases in discharge frequency in paradoxical sleep, with grouped spikes during oculomotor activity, appeared to be responsible for generating the phasic phenomena of paradoxical sleep. The question of the involvement of neurons of different populations in the mechanisms of paradoxical sleep is discussed.     

Relationship between Bioelectric Activity of Neurons in the Gigantocellular Nucleus of the Medulla Oblongata and Spontaneous Movements of Chick Embryo

Electrophysiological study revealed a correlation between changes in bioelectric activity of the reticular gigantocellular nucleus and movements of chick embryos during ontogeny (16-20 days). This relationship increased by the end of embryogenesis. The reticular gigantocellular nucleus is the major source of supraspinal influences on motor activity during ontogeny. Blockade of proprioceptive impulses with myorelaxin inhibited bioelectric activity of the regulatory gigantocellular nucleus, which attests to the activating effect of proprioception.