The limbical mechanisms of regulations of respiratory neurons in hypoxia conditions

The structures of limbic system have great integration in vegetative reactions. In the oxygen deficiency conditions we studied influence of irritation of limbical cortex, orbitofrontal cortes, hipotalamys, septum and hippocampus (CA1 and CA3 areas) on the impulse activity of respiratory neurons. Phases of hypoxia were the model of experiment. Irritation some of this structures on normoxia and 4-5 thousand meters higher, we discover inhibiting influense on respiratory neurons; some structures irritation had activating influence. In difficult conditions of hypoxia (7.5-8 thousand meters) on the reduction of the impulse activity of neurons, stimulation induced uncharacteristic reactions. Those different reactions of irritation limbic structures have regulation sense on respitatory neurons.     

Ventral Tegmental Area Inactivation Suppresses the Expression of CA1 Long Term Potentiation in Anesthetized Rat

The hippocampus receives dopaminergic projections from the ventral tegmental area (VTA). Modulatory effect of dopamine on hippocampal long term potentiation (LTP) has been studied before, but there are conflicting results and some limitations in previous reports. Most of these studies show a significant effect of dopamine on the late phase of LTP in CA1 area of the hippocampus, while few reports show an effect on the early phase. Moreover, they generally manipulated dopamine receptors in the hippocampus and there are few studies investigating influence of the VTA neural activity on hippocampal LTP in the intact brain. Besides, VTA neurons contain other neurotransmitters such as glutamate and GABA that may modify the net effect of dopamine. In this study we examined the effect of VTA reversible inactivation on the induction and maintenance of early LTP in the CA1 area of anesthetized rats, and also on different phases of learning of a passive avoidance (PA) task. We found that inactivation of the VTA by lidocaine had no effect on CA1 LTP induction and paired-pulse facilitation, but its inactivation immediately after tetanic stimulation transiently suppressed the expression of LTP. Blockade of the VTA 20 min after tetanic stimulation had no effect on the magnitude of LTP. Moreover, VTA inactivation immediately after training impaired memory in the passive avoidance task, while its blockade before or 20 min after training produced no memory deficit. It can be concluded that VTA activity has no effect on CA1 LTP induction and acquisition of PA task, but involves in the expression of LTP and PA memory consolidation.     

Response of respiratory neurons of the medulla oblongata to the septum stimulation in hypoxia

In the oxygen deficiency conditions, we studied influence of irritation of ventral (BNST), lateral (LSN) and medial (MSN) nuclei of the septum on the impulse activity of the bulbar respiratory neurons and on respiration. Phases of hypoxia were the model of experiment. In conditions of normal atmospheric pressure, the electrical stimulation of BNST, LSN and MSN nuclei of the septum exerted inhibiting as well as activating influence with the inhibiting influence prevailing. In difficult conditions of hypoxia (7.5-8 thousand meters) on the reduction of the impulse activity of neurons, stimulation of septum nucleuses induced uncharacteristic reactions of those neurons.     

Effects of basolateral amygdalar nuclei on neuronal activity in the medullary respiratory center under hypoxia conditions

The effect of stimulation of the basolateral nuclei of the amygdala (ABL) on the impulse activity of respiratory neurons (RNs) of the rat medulla and the respiratory function was studied in the norm and under conditions of oxygen deficiency. Electrical stimulation of the ABL under conditions of normal atmospheric pressure exerted ambivalent effects on bulbar RNs; both activation and inhibition of these neurons were observed, but inhibitory effects noticeably prevailed. Electrical stimulation of the ABL within an initial phase of hypobaric hypoxia corresponding to ascent to a 4,000 to 5,000 m altitude exerted mostly inhibitory effects on the RN activity (similarly to what was observed under normoxia conditions). Stimulation of these nuclei within a phase of intensive hypoxia (7,500 to 8,000 m) evoked no typical responses of such neurons against the background of hypoxic suppression of their activities. Neirofiziologiya/Neurophysiology, Vol. 38, No. 4, pp. 292–297, July–August, 2006.     

Effect of mediodorsal thalamic nucleus on the respiratory neurons from medulla oblongata and the rat respiration during hypoxia]

In the normal as well as in the oxygen deficiency conditions the research has been conducted to study the influence of associative mediodorsal (MD) nucleus of thalamus on impulsive activity of respiratory neurons of medulla oblongata of respiration. In conditions of normal atmospheric pressure, before the uplift of the animals, the electrical stimulation of MD of nucleus of thalamus has had mainly inhibiting influence. In the initial phase, on 4-5 thousand meter altitude, activation of frequent discharge of neurons occurred, the respiration has become frequent as well. In this situation the inhibiting influence of stimulation of MD nucleus of thalamus was more accentuated than in conditions of normoxia. In the second phase, 7.5-8 thousand meters, the opposite occurred, i.e. reduction of respiratory center activity of medulla oblongata and thalamus. In this difficult conditions of hypoxia, a reduction of impulsive activity of neurons has been observed; the respiration was becoming slower and surface. Meanwhile, the inhibiting influence of thalamus was not significant.     

Activity dynamics and behavioral correlates of CA3 and CA1 hippocampal pyramidal neurons

The CA3 and CA1 pyramidal neurons are the major principal cell types of the hippocampus proper. The strongly recurrent collateral system of CA3 cells and the largely parallel-organized CA1 neurons suggest that these regions perform distinct computations. However, a comprehensive comparison between CA1 and CA3 pyramidal cells in terms of firing properties, network dynamics, and behavioral correlations is sparse in the intact animal. We performed large-scale recordings in the dorsal hippocampus of rats to quantify the similarities and differences between CA1 (n > 3,600) and CA3 (n > 2,200) pyramidal cells during sleep and exploration in multiple environments. CA1 and CA3 neurons differed significantly in firing rates, spike burst propensity, spike entrainment by the theta rhythm, and other aspects of spiking dynamics in a brain state-dependent manner. A smaller proportion of CA3 than CA1 cells displayed prominent place fields, but place fields of CA3 neurons were more compact, more stable, and carried more spatial information per spike than those of CA1 pyramidal cells. Several other features of the two cell types were specific to the testing environment. CA3 neurons showed less pronounced phase precession and a weaker position versus spike-phase relationship than CA1 cells. Our findings suggest that these distinct activity dynamics of CA1 and CA3 pyramidal cells support their distinct computational roles.     

Effect of stimulation of field CA3 in the dorsal hippocampus on the motor polarization dominant in rabbits

The influence was studied of the stimulation of the CA3 field of the dorsal hippocampus on the course of motor polarization dominant created by the action of the direct current on the rabbit's cortical sensorimotor area. It is shown that hippocampus stimulation by 1 mA current (0.5 ms, 100 Hz, 0.2 s) against the background of the dominant optimum elicits its inhibition. It is manifested in depression of the motor "dominant" reaction of the forelimb to testing stimuli and in abolition of coherent connections of theta-range electrical activity of the sensorimotor cortex and CA3 field of the dorsal hippocampus. On the contrary, the hippocampus stimulation by a weak current (30-50 mcA, 0.5 ms, 30 Hz, 0.2 s) during optimum dominant reinforces it, eliciting a movement of the "dominant" limb. Against the background of an unstable dominant it provides for its activation and stabilization and recovers the dominant in the following days during its extinction.     

Corticosterone Has a Permissive Effect on Expression of Heme Oxygenase-1 in CA1–CA3 Neurons of Hippocampus in Thermal-Stressed Rats

Abstract: Activity of the stress protein, heme oxygenase-1 (hsp32; HO-1), produces carbon monoxide (CO), the potential messenger molecule for excitatory N -methyl- d -aspartate receptor-mediated events, in the hippocampus. Long-term stress caused by elevated adrenocorticoids induces pathological changes in CA1–CA3 neurons, of the hippocampus; the adrenal hormones also exacerbate damage from stress. In rats chronically treated with corticosterone, we examined expression of HO-1 and its response to thermal stress in the hippocampus. An unprecedented appearance of scattered immunoreactive astrocytes marked the molecular layer of the hippocampus in corticosterone-treated rats. Steroid treatment showed no discernible effect on whole-brain HO-1 mRNA. When these rats were subjected to hyperthermia, neurons in the CA1–CA3 area, including pyramidal cells, exhibited intense immunoreactivity for the oxygenase and a pronounced increase (∼10-fold) in number. HO-1 is essentially undetectable in this area when rats are exposed to chronic corticosterone alone or thermal stress by itself, or in control rats. In contrast, similar analysis of hilar neurons showed no apparent effect on either the number or relative intensity of HO-1-immunostained cells after treatment. Corticosterone treatment also intensified the stress response of cerebellum, including Purkinje cells and Bergmann glia in the molecular layer. In brain, despite a pronounced reduction in NO synthase activity in corticosterone-treated and/or heat-stressed animals, the level of cyclic GMP was not significantly reduced. These observations are consistent with the hypothesis that responsiveness to environmental stress of CA1–CA3 neurons brought about by chronic elevation in circulating adrenocorticoids results in an increased excitatory neuronal activity and eventual hippocampal degeneration. Moreover, these findings yield further support for a role of CO in the production of cyclic GMP in the brain.     

The role of Schaffer's collaterals in the sensory responses of the neurons of hippocampal field CA1]

In experiments with extracellular recording from the field CA1 pyramidal neurons in unanaesthetized rabbits the functional role of the Schaffer's collaterals (Sc) was investigated. Simultaneous presentation of sensory stimuli and Sc stimulation uniformly resulted in increase in duration of the post-excitatory inhibitory phase. In experiments with electrolytic lesion of the CA3 in the hippocampal segment, where recording from the CA1 was performed, background neuronal activity was normal. Reactions to sensory stimuli were preserved and had typical of the CA1 differentiated characteristics. The number of neurons with inhibitory responses to sensory stimuli was reduced. Habituation of responses was almost absent. Gradual increase in reactions duration up to prolonged increase of the background activity level was observed with repeated presentations of the stimuli. It is suggested that the influences of the field CA3 (through Sc) are not necessary for organization of sensory reactions in the CA1, but somehow participate in their limitation and inhibition.     

Origin of Ischemia-Induced Glutamate Efflux in the CA1 Field of the Gerbil Hippocampus: An In Vivo Brain Microdialysis Study

Abstract: In vivo brain microdialysis experiments were performed in the gerbil to evaluate the origin of accumulation of extracellular glutamate under transient ischemia. Microdialysis probes were positioned in the CA1 field of the hippocampus in which proliferation of astrocytes, death of CA1 pyramidal neurons, and damage of presynaptic terminals had been induced by 5-min ischemia 10–14 days before the microdialysis experiment; in the white matter of the cerebral cortex, which contained few neurons, few presynaptic terminals, and many astrocytes; or in the histologically normal CA1 field of the hippocampus, and then 5- or 20-min ischemia was induced. When 5-min ischemia was induced, no significant increase in glutamate content was observed in the CA1 field that showed proliferation of astrocytes, death of CA1 pyramidal neurons, and damage of presynaptic terminals and in the white matter of the cerebral cortex, whereas a significant increase in glutamate (15-fold) was observed in the histologically normal CA1 field. When 20-min ischemia was induced, no significant increase in glutamate content was observed in the CA1 field that showed proliferation of astrocytes, death of CA1 pyramidal neurons, and damage of presynaptic terminals and in the white matter during the first 10 min after the onset of 20-min ischemia, but remarkable ischemia-induced increases in glutamate were observed during the last 10 min of 20-min ischemia in both areas. An excessive increase in glutamate (100-fold) was observed during 20-min ischemia in the normal CA1 field of the hippocampus. When a probe was positioned in the CA1 field of the hippocampus in which presynaptic terminals of Schaffer collaterals and commissural fibers had been eliminated by bilateral kainate injections into the lateral ventricles 4–7 days before the microdialysis experiment and then 5-min ischemia was induced, a significant increase in glutamate was observed during the last half of 5-min ischemia. These results suggest that the efflux of glutamate from astrocytes does not contribute to the large ischemia-induced glutamate accumulation in the CA1 field of the hippocampus during 5-min ischemia but contributes to the ischemia-induced increase in glutamate level during ischemia with a longer duration and that ischemia-induced efflux of glutamate in the CA1 field during 5-min ischemia originates mainly from neuronal elements: presynaptic terminals and postsynaptic neurons.     

Comparative analysis of neuronal impulse activity in the CA1 and CA3 hippocampal fields in various typological groups of rats under exposure to emotional stimuli

Hippocampal unit activity in the right and left CA1 and CA3 fields was studied in rats divided in two groups by the method of "emotional resonance": the animals which did ("A") and did not stop ("E") crying of a partner rat. The rate of neuronal firing was studied in the state of hunger, satiation, and under exposure to intracranial electrical stimulation of the emotional positive and negative structures of the brain. It was shown that units increasing their activity after satiation prevailed in the CA1 field, whereas, in the CA3 field, the majority of neurons decreased the firing rate under these conditions. Intracranial stimulation, especially positive, increased the rate of firing in both hippocampal fields. Under exposure to emotional stimuli, "A" rats displayed asymmetric unit activity only in the CA1 field, whereas in "E" rats, activity was asymmetric only in the CA3 field. Under these conditions in both groups of animals, the left-side activity was more intense than the right-side activity independently of the emotion sign.     

Comparison of direct influences of the perforant path on hippocampal CA1 and CA3 neurons in vitro

The efficiency of synapses of the perforant path located on terminals of apical dendrites of CA₁ and CA₃ neurons was investigated in sections of the guinea pig hippocampus in vitro. Neurons of both areas were shown to respond to stimulation of the perforant path by action potential generation. Responses of most CA₁ neurons appeared to repetitive stimulation with a frequency of up to 30–80/sec. Neurons in area CA₃ respond only to low-frequency stimulation (under 5/sec). Posttetanic potentiation of responses to stimulation of the perforant path was found in both areas of the hippocampus.Institute of Biophysics, Academy of Sciences of the USSR, Pushchino-on-Oka. Translated from Neirofiziologiya, Vol. 11, No. 4, pp. 303–310, July–August, 1979.     

Protective effect of hypothermia on brain neurons of rats exposed to ionizing radiation

The conditions of the protein-synthesizing system in neurons of the hippocampus (areas CA1 and C A3) and of the cortex (sensomotor region) in rats subjected to y-irradiation at a dose of 8 Gy under hypothermia (16 - 18 degrees C) and hypoxia-hypercapnia were investigated by fluorescent and electron microscopy. Under hypothermia, the protein-synthesizing system was shown to be damaged to a lesser degree and to be restored faster in comparison with similar neurons in rats irradiated at room temperature. In rats irradiated under hypothermia, the rRNA biogenesis and the protein-synthesizing activity of polyribosomes were restored in two days. The protective influence of hypothermia did not spread to changes in membrane structures (endoplasmic reticulum and Golgy apparatus); i.e., a partial loss of integrity and possible transformation of their structure caused by the irradiation and the restoration of these structures occurred at a lower rate.     

Prenatal Nicotine and Maternal Deprivation Stress De-Regulate the Development of CA1, CA3, and Dentate Gyrus Neurons in Hippocampus of Infant Rats

Adverse experiences by the developing fetus and in early childhood are associated with profound effects on learning, emotional behavior, and cognition as a whole. In this study we investigated the effects of prenatal nicotine exposure (NIC), postnatal maternal deprivation (MD) or the combination of the two (NIC+MD) to determine if hippocampal neuron development is modulated by exposure to drugs of abuse and/or stress. Growth of rat offspring exposed to MD alone or NIC+MD was repressed until after weaning. In CA1 but not CA3 of postnatal day 14 (P14) pups, MD increased pyramidal neurons, however, in dentate gyrus (DG), decreased granule neurons. NIC had no effect on neuron number in CA1, CA3 or DG. Unexpectedly, NIC plus MD combined caused a synergistic increase in the number of CA1 or CA3 neurons. Neuron density in CA regions was unaffected by treatment, but in the DG, granule neurons had a looser packing density after NIC, MD or NIC+MD exposure. When septotemporal axes were analyzed, the synergism of stress and drug exposure in CA1 and CA3 was associated with rostral, whereas MD effects were predominantly associated with caudal neurons. TUNEL labeling suggests no active apoptosis at P14, and doublecortin positive neurons and mossy fibers were diminished in NIC+MD relative to controls. The laterality of the effect of nicotine and/or maternal deprivation in right versus left hippocampus was also analyzed and found to be insiginificant. We report for the first time that early life stressors such as postnatal MD and prenatal NIC exposure, when combined, may exhibit synergistic consequences for CA1 and CA3 pyramidal neuron development, and a potential antagonistic influence on developing DG neurons. These results suggest that early stressors may modulate neurogenesis, apoptosis, or maturation of glutamatergic neurons in the hippocampus in a region-specific manner during critical periods of neurodevelopment.     

Long-lasting changes in the density of nitrergic neurons following kainic acid administration and chronic hypoxia

Using histochemical analysis (NADPH-diaphorase) we have investigated the influence of intraperitoneal administration of kainic acid (KA), hypoxia and combination of both these factors on neurons of the hippocampus and on the primary auditory cortex (PAC) in male rats of the Wistar strain. Kainic acid was administered to 18-day-old animals, which were exposed to long-lasting repeated hypoxia from the 2nd till the 17th day of age in a hypobaric chamber (for 8 hours a day). At the age of 1 year, the animals were transcardially perfused with 4 % paraformaldehyde under deep thiopental anesthesia. Cryostate sections were stained to identify NADPH-diaphorase positive neurons that were then quantified in CA1 and CA3 areas of the hippocampus, in the dentate gyrus and in the PAC. Both, hypoxia and KA lowered the number of NADPH-diaphorase positive neurons in the hilus, dorsal and ventral blades of the dentate gyrus, CA1 and CA3 areas of the hippocampus. On the contrary, KA given to the hypoxic animals increased the number of NADPH-diaphorase positive neurons in the dorsal blade of the dentate gyrus and PAC.     

High expression of GLT-1 in hippocampal CA3 and dentate gyrus subfields contributes to their inherent resistance to ischemia in rats

It is well known that neurons in the CA3 and dentate gyrus (DG) subfields of the hippocampus are resistant to short period of ischemia which is usually lethal to pyramidal neurons in hippocampal CA1 subfield. The present study was undertaken to clarify whether the inherent higher resistance of neurons in CA3 and DG to ischemia is associated with glial glutamate transporter-1 (GLT-1) in rats. Western blot analysis and immunohistochemistry assay showed that the basal expressions of GLT-1 in both CA3 and DG were much higher than that in CA1 subfield. Mild global brain ischemia for 8 min induced delayed death of almost all CA1 pyramidal neurons and marked GLT-1 down-regulation in the CA1 subfield, but it was not lethal to the neurons in either CA3 or DG and induced GLT-1 up-regulation and astrocyte activation showed normal soma and aplenty slender processes in the both areas. When the global brain ischemia was prolonged to 25 min, neuronal death was clearly observed in CA3 and DG accompanied with down-regulation of GLT-1 expression and abnormal astrocytes represented with hypertrophic somas, but shortened processes. After down-regulating of GLT-1 expression and function by its antisense oligodeoxynucleotides or inhibiting GLT-1 function by dihydrokainate, an inhibitor of GLT-1, the mild global brain ischemia for 8 min, which usually was not lethal to CA3 and DG neurons, induced the neuronal death in CA3 and DG subfields. Taken together, the higher expression of GLT-1 in the CA3 and DG contributes to their inherent resistance to ischemia.     

Parvalbumin Immunoreactivity and Protein Level are Altered in the Gerbil Hippocampus During Normal Aging

Hippocampal interneurons are local circuit neurons which are responsible for inhibitory activity in the hippocampus. Parvalbumin (PV) is one of useful markers for GABAergic interneurons, not for principle cells, in the hippocampus. In the present study, we investigated age-related changes in PV immunoreactive neurons and protein levels in the gerbil hippocampus during normal aging. PV immunoreactive neurons were detected in all hippocampal subregions of all groups. PV immunoreactive neurons, which innervated principal neurons, were non-pyramidal neurons in the hippocampal CA1-3 regions, and were polymorphic neurons in the dentate gyrus. In the hippocampal CA1 region, the number of PV immunoreactive neurons was significantly reduced in the postnatal month 3 (PM 3) group, which was sustained by PM 18, and, at PM 24, the number of PV immunoreactive neurons was significantly decreased. In the CA2/3 region and dentate gyrus, the number of PV immunoreactive neurons was significantly decreased at PM 6: Thereafter, the number of PV immunoreactive neurons was sustained until PM 24. In addition, changes in PV protein levels in the gerbil hippocampus were similar to immunohistochemical changes during normal aging: PV protein levels were significantly decreased with age by PM 6: Thereafter, PV protein levels were sustained by PM 24. These results suggest that PV immunoreactive interneurons were decreased in the hippocampus with age in gerbils.     

Neurotrophin expression in rat hippocampal slices: a stimulus paradigm inducing LTP in CA1 evokes increases in BDNF and NT-3 mRNAs.

We report that stimulation inducing long-term potentiation (LTP) in the CA1 pyramidal cell layer of the hippocampus evokes significant increases in both BDNF and NT-3 mRNAs in CA1 neurons. No changes in BDNF or NT-3 mRNA levels were seen in the nonstimulated regions of the pyramidal cell layer or the dentate. No change was seen in the levels of NGF mRNA at the time point examined. These results suggest that relatively normal levels of activity may regulate region-specific neurotrophin levels in the hippocampus. Given that known effects of NGF (and presumably of BDNF and NT-3) include elevation of neurotransmitter levels, elevation of sodium channels, and promotion of axonal terminal sprouting, activity-associated changes in neurotrophin levels may play a role in regulating neural connections in the adult as well as the developing nervous system.     

Morphological changes in the hippocampus following nicotine and kainic acid administration

Using histochemical analysis (NADPH-diaphorase, Fluoro-Jade B dye and bis-benzimide 33,342 Hoechst) we studied the influence of intraperitoneal administration of nicotine (NIC), kainic acid (KA) and combination of both these substances on hippocampal neurons and their changes. In experiments, 35-day-old male rats of the Wistar strain were used. Animals were pretreated with 1 mg/kg of nicotine 30 min prior to the kainic acid application (10 mg/kg). After two days, the animals were transcardially perfused with 4 % paraformaldehyde under deep thiopental anesthesia. Cryostat sections were stained to identify NADPH-diaphorase positive neurons that were then quantified in the CA1 and CA3 areas of the hippocampus, in the dorsal and ventral blades of the dentate gyrus and in the hilus of the dentate gyrus. Fluoro-Jade B positive cells were examined in the same areas in order to elucidate a possible neurodegeneration. In animals exposed only to nicotine the number of NADPH-diaphorase positive neurons in the CA3 area of the hippocampus and in the hilus of the dentate gyrus was higher than in controls. In contrast, KA administration lowered the number of NADPH-diaphorase positive cells in all studied hippocampal areas and in both blades of the dentate gyrus. Massive cell degeneration was observed in CA1 and CA3 areas of the hippocampus and in the hilus of the dentate gyrus after kainic acid administration. Animals exposed to kainic acid and pretreated with nicotine exhibited degeneration to a lesser extent and the number of NADPH-diaphorase positive cells was higher compared to rats, which were exposed to kainic acid only.     

Neocortex neuron reactions caused by stimulation of the substantia innominata in cats

We investigated neuronal impulse activity in the sensorimotor cortex after substantia innominata (SI) stimulation in cats during the execution of an instrumental conditioned response consisting of placement of a paw on a pedal coupled with alimentary reinforcement. Stimulation of the SI was initiated 1 or 3 sec prior to conditioned stimulation. Background activity of the neurons was inhibited during stimulation of the SI. Preliminary stimulation of the SI one second in advance caused an increase of reactions linked to a subsequent conditioned stimulus and a conditioned-response movement in 32% of the neurons; a 3-sec lead caused increases of such reactions in 33% of neurons. In some cells which originally did not react to the conditioned excitation, a clear reaction did manifest after stimulation. Moreover, stimulation of the SI with a 1-sec lead caused inhibition of impulse reactions in 6% of the cells; with a 3-sec lead, it caused inhibition of impulse reactions in 33% of the cells. The spread of latencies of conditioned-response actions decreased 2- to 3-fold in this case. We discuss the possibility that acetylcholine, which is released by the terminals of cholinergic neurons of the SI, has a facilitating influence on the impulse activity of neocortical neruons.Bogomolets Institute of Physiology, Ukrainian Academy of Sciences, Kiev. Translated from Neirofiziologiya, Vol. 24, No. 1, pp. 11–20, January–February, 1992.