Reflection of the operations of comparison of current afferentation with internal pretuning in the impulse activity of neurons of the frontal cortex of the dog

When the differentiation of the classical (salivary) conditioned reflex (CR) is carried out by dogs, two groups of neurons are distinguished in their frontal cortex, for which a specific type of relationships between the current conditional and unconditional (CS and US) signals and the character of the internal pretuning to the pereception of the given stimuli is the condition. The reactions of the neurons of the first group developed in response to the US only when the tracking schedule of the US was characterized by regularity. These reactions disappeared when there was any sudden deviation from the standard schedule of the of the CS-US combination for the animal, or when there was a change in the parameters of these signals, and they recovered as the repeated presentations of the CS or the US with the changed parameters proceeded. The reactions of the neurons of the second group developed in response to the presentation of the CS only when this stimulus followed a stimulus which was opposite to it in significance. The reactions of the neurons of the first group are associated with the processes of the detection of the correspondence of the sensory pretuning to the actual stimulus, while the reactions of the neurons of the second group are regarded as the result of the disparity between the characteristics of the current afferentation and the internal model of the stimulus.Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti imeni I. P. Pavlova, Vol. 40, No. 2, pp. 331–339, March–April, 1990.     

Age-related alterations in responses of the nucleus basalis magnocellularis neurons to frontal cortex stimulation in rats

The present study investigated the age-related alterations in responses of the nucleus basalis magnocellularis (nbM) neurons to frontal cortex (FCX) stimulation. Single unit extracellular recording from the nbM neurons were obtained with glass micropipettes in urethane-anesthetized rats. A total of 137 units were located within the nbM in the three age groups (young, 3 months; adult, 12 months; old, 24 months). FCX stimulation elicited responses in 91% of the 137 neurons. Most of them were excited. The frequency of occurrence of excitatory responses in the nbM neurons was decreased with aging. The thresholds and latencies of excitatory responses evoked by FCX stimulation were increased in old rats. The mean peak-firing rate of exciting phase was gradually reduced with aging. These findings indicate that there might be some functional changes in the nbM neurons with aging.     

Reflection of the systemic mechanisms of instrumental behavior in the activity of brain neurons

Changes in the impulse activity of neurons of the sensorimotor, parietal associative, and visual areas of the cerebral cortex were studied during the performance of conditioned instrumental alimentary behavior by an animal. Comparative analysis of impulse activity of the neurons investigated showed that 71.4% of the cells of the parietal associative area of the cerebral cortex were activated when the conditional stimulus was turned on; 75.8% of neurons of the visual cortex were activated when the animal pressed the pedal; 82.5% of the cells of the somatosensory and 75.8% of the visual area of the cerebral cortex increased activity upon appearance of milk in the food dispenser. During lapping of the milk, 75.8% of cells of the visual cortex showed reduction of activity. Reorganization of the impulse activity of individual neurons of the cerebral cortex reflected the unfolding of pretriggering integration formed as the result of preliminary training of the animal. The character of the impulse activity of the neurons investigated at the stage of realization of the program of the action and obtaining of reinforcement was determined primarily by the streams of afferent excitations arising during the perception of parameters of the stage-related and final results of the behavior. Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti imeni I. P. Pavlova, Vol. 43, No. 2, pp. 333–340, March–April, 1993.     

Subthreshold inward membrane currents in guinea-pig frontal cortex neurons

Current-clamp and single-electrode voltage-clamp recordings were used to study the inward currents activated in the subthreshold membrane potential range of cortical pyramidal neurons. The experiments were done on slices from guinea-pig frontal cortex and all recordings were obtained at a distance of 600–900 μm from the pial surface. In current-clamp recordings and from membrane potentials hyperpolarized to about −70 mV, the depolarization leading to spike firing was partially blocked by 1 μM tetrodotoxin, but not by calcium-free extracellular solution. The calcium-free solution only affected this depolarization when the membrane potential was held at a level more negative than −75 mV. Under voltage-clamp, an inward current was recorded between the resting membrane potential and the level of spike firing. This current was activated at about −60 mV and part of it was blocked by 1 μM tetrodotoxin; the remaining current was blocked by calcium-free extracellular solution. In five neurons both components were recorded and isolated in the same cell. The tetrodotoxin-sensitive component activated at close to −60 mV, was similar to the persistent sodium current (I_Na-p). The Ca²⁺-sensitive component activated at close to −60 or −65 mV, was less voltage-dependent than I_Na-p. This component was similar to the low threshold calcium current (I_T).These results suggest that the subthreshold depolarization which led to spike firing was dependent on I_Na-p and I_T, I_Na-p being the most important factor up to resting membrane potentials of −70 or −75 mV. A physiological role of this finding is revealed by the action of dopamine, which (at 10 μM) prevented the firing of action potentials from −60 mV, but not from −80 mV due to the inhibition of I_Na-p and the lack of effect on I_T.     

Subthreshold inward membrane currents in guinea-pig frontal cortex neurons

Current-clamp and single-electrode voltage-clamp recordings were used to study the inward currents activated in the subthreshold membrane potential range of cortical pyramidal neurons. The experiments were done on slices from guinea-pig frontal cortex and all recordings were obtained at a distance of 600-900 microm from the pial surface. In current-clamp recordings and from membrane potentials hyperpolarized to about -70 mV, the depolarization leading to spike firing was partially blocked by 1 microM tetrodotoxin, but not by calcium-free extracellular solution. The calcium-free solution only affected this depolarization when the membrane potential was held at a level more negative than -75 mV. Under voltage-clamp, an inward current was recorded between the resting membrane potential and the level of spike firing. This current was activated at about -60 mV and part of it was blocked by 1 microM tetrodotoxin; the remaining current was blocked by calcium-free extracellular solution. In five neurons both components were recorded and isolated in the same cell. The tetrodotoxin-sensitive component activated at close to -60 mV, was similar to the persistent sodium current (I(Na-p)). The Ca2+-sensitive component activated at close to -60 or -65 mV, was less voltage-dependent than I(Na-p). This component was similar to the low threshold calcium current (I(T)). These results suggest that the subthreshold depolarization which led to spike firing was dependent on I(Na-p) and I(T), I(Na-p) being the most important factor up to resting membrane potentials of -70 or -75 mV. A physiological role of this finding is revealed by the action of dopamine, which (at 10 microM) prevented the firing of action potentials from -60 mV, but not from -80 mV due to the inhibition of I(Na-p) and the lack of effect on I(T).     

STZ诱导的糖尿病大鼠额叶皮层内神经细胞线粒体损伤和DMT1高表达

目的:探讨1型糖尿病脑内自由基产生的铁代谢途径及线粒体氧化损伤水平。方法:利用链脲佐菌素(streptozotocin,STZ)股静脉单次注射(60 mg/kg)诱导大鼠糖尿病模型,2个月后检测血糖及脑脊液的葡萄糖水平。通过Western Blot技术检测额叶皮层内特异性转运蛋白(divalent metal transport,DMT1)及硫氧环蛋白1(thioredoxin,TR1)的表达水平;分离神经细胞线粒体,检测线粒体中丙二醛(malonaldehyde,MDA)及谷胱甘肽(glutathione,GSH)的含量。结果:与正常组比较,STZ诱导的糖尿病模型大鼠在2个月时的血糖和脑脊液葡萄糖水平持续升高(P0.05),前额叶皮层DMT1表达增加,而TR1的表达减少(P0.05)。同时还观察到额叶皮层神经细胞线粒体GSH水平下降,而MDA的水平升高(P0.05)。结论:糖尿病导致的神经细胞损伤和自由基累积关系密切,而铁代谢异常可能是原因之一,线粒体损伤可能是启动因素。     

Single unit activity in frontal cortex and caudate nucleus of young and old rats

Spontaneous neuronal activity was recorded extracellularly from isolated single units in frontal neocortex and caudate nucleus of young and aged F344 rats anesthetized with urethane. Average firing rates, mean interspike intervals (ISI)±standard deviations, and ISI frequency histograms were computed and analyzed by microprocessor. For frontal cortex cells (N=226), there was a nonsignificant trend toward slower average discharge rates in the old group. However, a significantly longer mean ISI and proportionally more very slow firing cells (<I Hz) were observed in old rats. A laminar analysis of frontal cortex unit activity in young animals showed average discharge rates to be distributed somewhat evenly throughout the cortical mantle with the exception of the zone 1200–1400 μ beneath brain surface. This depth corresponds approximately to layer V where a 50% increase in mean firing rate in young animals was observed. In aged animals, this increased cell firing in layer V was absent, while mean discharge rates in other laminae remained essentially the same in the young and old rat groups. Caudate nucleus cells (n=70) showed a significant shift towards fewer fast discharging cells in old rats, with the average firing rate diminished by one-third. Although more brain regions need to be examined in a similar fashion, the consistency of the present results with those previously reported for the brainstem and cerebellum suggests that slower firing rates and longer ISIs are likely to be wide-spread throughout the brains of aged rats.     

Disturbances in the integrative activity of the rat brain after bilateral focal compression ischemia of the frontal cortex

Pathomorphological changes and disturbances in the integrative activity of the central nervous system of rats are studied after bilateral compression ischemia of the frontal cortex. Bilateral compression of the frontal cortex is shown to result in the formation of limited foci of ischemic necroses in the cortex, which are surrounded by the perifocal zone. This is attended by reduced horizontal motor activity in the “open field” test, as well as by a reduced latency of the conditioned passive avoidance response. The motor activity of operated animals is restored on day 14 postoperation, correlating with regeneration of some damaged neurons in the perifocal zone, whereas the latency of the conditioned passive avoidance response remains markedly reduced. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 118, N ^o 12, pp. 568–571, December, 1994 Presented by O. S. Adrianov, Member of the Russian Academy of Medical Sciences     

Nicotinic cholinoceptive neurons of the frontal cortex are reduced in Alzheimer's disease

The cellular distribution of nicotinic acetylcholine receptors was studied in the frontal cortex (area 10) of 1) Alzheimer patients and compared to 2) age-matched and 3) middle-aged controls using the monoclonal antibody WF 6 and an immunoperoxidase protocol. Statistical analysis revealed significant differences between the number of labeled neurons among all three groups tested (middle-aged controls greater than aged controls greater than Alzheimer cases). No differences were seen for cresyl violet-stained samples. These findings underline that the nicotinic receptor decrease found with radioligand binding may reflect a postsynaptic in addition to a presynaptic component.     

Responses of cat vestibular neurons to stimulation of the frontal cortex

Summary To study the neural basis for the regulation of vestibulocollic reflexes during voluntary head movements, the effects of stimulation of the precruciate cortex near the presylvian sulcus (neck area of the motor cortex) and the frontal eye fields (FEF) on vestibular neurons were studied in cerebellectomized cats anesthetized with chloralose. Neurons were recorded in the medial and descending vestibular nuclei and antidromically identified from C₁. Stimulation of the FEF and precruciate cortex fired 29 and 13% of neurons that did not exhibit spontaneous activity. About 80% of spontaneously discharging neurons were influenced by stimulation of either of the two. Stimulation of the precruciate cortex or FEF suppressed or facilitated labyrinthine evoked monosynaptic activation of vestibulospinal neurons, suggesting that the frontal cortical neurons have the properties to regulate the vestibulocollic reflexes.     

Microglial reactions to retrograde degeneration of tracer-identified thalamic neurons after frontal sensorimotor cortex lesions in adult rats

Thalamic neuronal degeneration after neocortical lesions involve both anterograde and retrograde components. This study deals with the thalamic microglial response after neocortical aspiration lesions, using fluorogold fluorescent prelabeling, to identify retrogradely degenerating thalamocortical neurons, combined with histochemical or immunohistochemical staining of microglial cells. Adult male Wistar rats were injected with the retrograde fluorescent tracer fluorogold, in the right sensorimotor cortex (forepaw area) in order to retrogradely label thalamic neurons projecting to this area. After 1 week, the fluorogold injection site was removed by aspiration, axotomizing at the same time the thalamic projection neurons now retrogradely labeled with fluorogold. After 3, 7, 14, and 28 days the animals were killed and processed for nucleoside diphosphatase histochemistry or complement type 3 receptor immunohistochemistry and class I and II major histocompatibility complex immunohistochemistry using OX42, OX18, and OX6 antibodies. The histological analysis showed a prominent and progressive nucleoside diphosphatase-,OX42-, and OX6-positive microglial cell response in the ventrolateral, posterior, and ventrobasal thalamic nuclei with ongoing retrograde and anterograde neuronal degeneration. Initially the reactive microglia had a bushy morphology and were succeeded by ameboid microglia and microglial cluster cells as the reaction progressed. However, in the reticular thalamic nucleus, which suffered exclusively anterograde neuronal degeneration, a different picture was seen with only bushy microglia. The neurons undergoing retrograde degeneration in the ventrolateral, posterior, and ventrobasal thalamic nuclei were retrogradely labeled by the fluorogold tracer. Individual nucleoside diphosphatase-, OX42-, or OX6-positive microglial cells extended long cytoplasmic processes surrounding fluorogold-labeled neurons and had in some cases apparently phagocytized these. Several microglial cells were thus double-labeled with nucleoside diphosphatase or OX42 and fluorogold. In addition, small nucleoside diphosphatase-positive, fluorogold-labeled perivascular cells were observed in the neocortex near the fluorogold-injected and ablated neocortical areas and in the ipsilateral thalamus. This study demonstrates: (1) that the microglial response to thalamic degeneration after neocortical lesion is graded with a limited reaction to the well-known massive anterograde axonal degeneration and a more extended reaction to the axotomy-induced retrograde cell death; and (2) that also perivascular cells and possibly macrophages may contribute to this reaction, as seen by uptake of fluorogold from axotomized neurons in the degenerating thalamic nuclei.     

Neurotensin-induced excitation of neurons of the rat's frontal cortex studied intracellularly in vitro

Summary The actions of neurotensin (NT) on frontal pyramidal neurons were studied in vitro in slices of rat cerebral cortex using current clamp and single electrode voltage clamp (SEVC) techniques. Bath application of NT (0.1 M–10 M) induced a depolarization (2–13 mV) in 88% of the pyramidal cells, this effect was associated with a decrease in input conductance of 5–35% and its reversal potential was estimated at -88 +/-9.7mV. Typically, this depolarizing effect of NT was transient, since no cell responded to a second application of the peptide within 20 min after the first one. NT also induced an increase in the rate of firing of pyramidal cells evoked by direct stimulation, even when an hyperpolarizing current was applied to prevent the depolarization induced by NT. This effect could neither be explained by a decrease of the post-spike after-hyperpolarization, nor by an increase of the persistent sodium current which sustains the spiking of pyramidal cells, since the former was not affected consistently by NT and the later was insensitive to the peptide. This excitation of pyramidal neurons by NT persisted after blockade of synaptic transmission. On the other hand, NT also enhanced the synaptic noise recorded in pyramidal cells in standard perfusing medium. Furthermore, dopaminergic antagonists and noradrenergic antagonists failed to block these effects of NT. Finally, the inactive fragment of the peptide, NT(1–8), did not affect membrane properties of pyramidal cells. All together, these results suggest that NT excites frontal cortical neurons through the activation of specific NT receptors.     

Oxidative modification of proteins in the frontal cortex of Alzheimer's disease brain

There is a large body of evidence highlighting the importance of oxidative stress in the pathogenesis of Alzheimer's disease (AD). We have previously standardised a method that can be applied to study oxidative changes in individual brain proteins by using two-dimensional oxyblots (Korolainen MA, Goldsteins G, Alafuzoff I, Koistinaho J, Pirttil? T. Proteomic analysis of protein oxidation in Alzheimer's disease brain. Electrophoresis 2002;23(19):3428-33). Here we have identified proteins that exhibited oxidative changes in AD when compared to age-matched controls and these protein changes have been further examined in relation to the neuropathological data. Indeed, several Tris-HCl soluble proteins tended to be less oxidised in AD when compared to controls. Two enzymes, mitochondrial glutamate dehydrogenase and cytosolic malate dehydrogenase, were increased in amount but showed significantly decreased degree of oxidation in AD brains when compared to controls. Furthermore, some changes related to the amounts or oxidation statuses of proteins were associated with the duration of the clinical impairment and also with the neuropathology. These results do not contradict the hypothesis of increased oxidative stress in AD but may represent co-existing compensatory changes in response to oxidative stress.     

Baseline and evoked spike activity in neurons in embryonic transplants of the somatosensory cortex in rats

The aim of the present work was to study the nature of the baseline and evoked spike activity of neurons in embryonic transplants four months after homotopic allotransplantation into the whisker representation zone of the somatosensory cortex of the recipient rat brain (the barrel field). These studies showed that the instantaneous mean spike frequency of neuron activity was decreased in neural transplants as compared with the somatosensory cortex of control rats, while the latent period of evoked cell activity was longer. In addition, the pattern of evoked activity in transplant neurons was characterized by an increased frequency of spike generation or alternation of periods of activation and decreased spike frequency with subsequent recovery to the initial level, this being similar to the pattern seen in neurons in the whisker representation zone of the somatosensory cortex in control rats. __________ Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 91, No. 5, pp. 473–480, May, 2005.     

Effects of gaze on apparent visual responses of frontal cortex neurons

Previous reports have argued that single neurons in the ventral premotor cortex of rhesus monkeys (PMv, the ventrolateral part of Brodmann's area 6) typically show spatial response fields that are independent of gaze angle. We reinvestigated this issue for PMv and also explored the adjacent prearcuate cortex (PAv, areas 12 and 45). Two rhesus monkeys were operantly conditioned to press a switch and maintain fixation on a small visual stimulus (0.2° × 0.2°) while a second visual stimulus (1° × 1° or 2° × 2°) appeared at one of several possible locations on a video screen. When the second stimulus dimmed, after an unpredictable period of 0.4–1.2s, the monkey had to quickly release the switch to receive liquid reinforcement. By presenting stimuli at fixed screen locations and varying the location of the fixation point, we could determine whether single neurons encode stimulus location in absolute space or any other coordinate system independent of gaze. For the vast majority of neurons in both PMv (90%) and PAv (94%), the apparent response to a stimulus at a given screen location varied significantly and dramatically with gaze angle. Thus, we found little evidence for gaze-independent activity in either PMv or PAv neurons. The present result in frontal cortex resembles that in posterior parietal cortex, where both retinal image location and eye position affect responsiveness to visual stimuli.     

Balance of neurotransmitter amino acids and integrative activity of the brain after local ischemic damage to the frontal cortex in rats: effects of glycine and piracetam

Bilateral local compression ischemia in the frontal rat brain cortex modifies the levels of neurotransmitter amino acids at the stage of most pronounced disorders in the brain integrative activity. In this model, neuroprotective properties of the drugs piracetam and glycine are evaluated. Glycine accelerates GABA turnover at the sites of ischemia as well as in the parietal cortex and hippocampus and, similar to piracetam, restores almost completely the conditioned response of passive avoidance impaired by ischemia. Glycine also reduces locomotor activity of both ischemic and sham-operated rats. It is suggested that normalizing effect of glycine on the functional balance of neurotransmitter amino acids immediately after ischemic damage to the cortex promotes restitution of disturbed functions of the central nervous system. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 123, No. 4, pp. 370–373, April, 1997     

Projections of somatosensory cortex and frontal eye fields onto incertotectal neurons in the cat

The goal of this study was to determine whether the input-output characteristics of the zona incerta (ZI) are appropriate for it to serve as a conduit for cortical control over saccade-related activity in the superior colliculus. The study utilized the neuronal tracers wheat germ agglutinin-horseradish peroxidase (WGA-HRP) and biotinylated dextran amine (BDA) in the cat. Injections of WGA-HRP into primary somatosensory cortex (SI) revealed sparse, widespread nontopographic projections throughout ZI. In addition, region-specific areas of more intense termination were present in ventral ZI, although strict topography was not observed. In comparison, the frontal eye fields (FEF) also projected sparsely throughout ZI, but terminated more heavily, medially, along the border between the two sublaminae. Furthermore, retrogradely labeled incertocortical neurons were observed in both experiments. The relationship of these two cortical projections to incertotectal cells was also directly examined by retrogradely labeling incertotectal cells with WGA-HRP in animals that had also received cortical BDA injections. Labeled axonal arbors from both SI and FEF had thin, sparsely branched axons with numerous en passant boutons. They formed numerous close associations with the somata and dendrites of WGA-HRP-labeled incertotectal cells. In summary, these results indicate that both sensory and motor cortical inputs to ZI display similar morphologies and distributions. In addition, both display close associations with incertotectal cells, suggesting direct synaptic contact. From these data, we conclude that inputs from somatosensory and FEF cortex both play a role in controlling gaze-related activity in the superior colliculus by way of the inhibitory incertotectal projection.     

Neuronal activity in dorsomedial frontal cortex and prefrontal cortex reflecting irrelevant stimulus dimensions

Previous studies of the dorsomedial frontal cortex (DMF) and the prefrontal cortex (PF) have shown that, when monkeys respond to nonspatial features of a discriminative stimulus (e.g., color) and the stimulus appears at a place unrelated to the movement target, neurons nevertheless encode stimulus location. This observation could support the idea that these neurons always encode stimulus location, regardless of its relevance to an instrumentally conditioned behavior. Past studies, however, leave open the possibility that activity observed during one operant task might reflect the contingencies of a different task, performed at different times. To test these alternatives, we examined the activity of DMF and PF neurons in two rhesus monkeys conditioned to perform an operant eye-movement task in which only the color and shape of visual stimuli served as salient discriminative features. Each of eight stimuli was associated with a response to a different eye-movement target. The location of these stimuli varied from trial to trial but was of no behavioral relevance, and the monkeys did not perform any operant task in which stimulus location controlled behavior. A substantial minority of neurons in both DMF and PF nevertheless encoded stimulus location, which indicates that this property does not depend on its relevance in an instrumentally conditioned behavior. Electronic Publication     

Neuronal activity of medial wall of frontal cerebral cortex of rats at various stages of learning

The activity of neurons of the medial wall of the frontal cortex of the brain of rabbits was investigated during their performance of a task of delayed spatial choice. The recording of neuronal activity was carried out in two groups of animals which were at different stages of training. Different types of spatially selective neurons were found. The possible association of the character of the neuronal reorganizations with the level of learning of the animal is discussed.Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti imeni I. P. Pavlova, Vol. 39, No. 6, pp. 1105–1111, November–December, 1989.