Change in reactions of visual cortex neurons to light flash upon hypothalamic and reticular stimulation

The effect of electrical stimulation of the hypothalamic positive reinforcement zone (PRZ), the neutral hypothalamic zone (NZ), and the reticular formation (RF), of the midbrain on the impulse activity of single neurons of the visual cortex evoked by light flashes was studied in unanesthetized and uncurarized white rats. Poststimulus histograms of the neurons's responses were compared. Under the influence of stimulation the evoked activity of the neurons which responded to light changed in a majority of them (from 63% for the NZ to 82% for the RF). Qualitative differences were found in the effects of PRZ and RF stimulation. The effects of PRZ stimulation consisted in the invariability or in a decrease in the frequency of the neuron's discharge comprising the short-latent response, and an increase in the frequency of the discharges in the long-latent response ("positive-motivation" type). The effects of RF stimulation were manifested in intensification of the neuronal discharges in the short-latent and a decrease in the discharges in the long-latent response ("reticular" type). The responses of a considerable number of the neurons changed to the "combined" type. The data obtained indicates the different natures and mechanisms of the ascending activating effects caused by stimulation of the PRZ and the RF and which brings about positive nonspecific reinforcements. These effects, which are manifested differently in different periods of the neuron's working cycle cannot be explained by "energizing" or "tonus" concepts; their explanation must be sought for in informational (systemic) concepts.N. I. Grashchenkov Laboratory of Problems of Functional Control in the Human and Animal Organism, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 3, No. 4, pp. 359–368, July–August, 1971.     

Emotional manifestations in the electrical stimulation of the hypothalamic nuclei in adult and old rats

In experiments on adult (9-10 months) and old (24-26 months) white Wistar rats behavioural manifestations under electrical stimulation of the ventromedial hypothalamus nucleus and self-stimulation (SS) of the lateral hypothalamic region were studied. It has been found that with age electrical thresholds of negative emotional manifestations decrease with invariable SS thresholds. In old rats, in comparison with the adult ones, SS frequency is lower, maximum SS proceeds at lower currents, the range of currents capable to evoke an intensive SS is narrower, SS motivational component is less expressed. The obtained data testify that in old rats there exist neurophysiological preconditions for prevailing of negative emotional manifestations.     

Substance P and the ethanol-evoked changes in the independent motivated behavioral reactions of rabbits

Ethanol (0.5 g/kg) administered intravenously led to alterations in central mechanisms of feeding and escape, elicited by threshold electrical stimulation either of lateral or of ventromedial hypothalamic centers of the rabbit. Subsequent intravenous injection of substance P (30 mcg/kg) restored the excitability of the ventromedial hypothalamus and facilitatory effects on this motivational center of the midbrain reticular formation. The restoration of both inhibitory influences of the dorsal hippocampus and facilitatory ones of the midbrain reticular formation on the excitability of the lateral hypothalamus was also observed after SP administration. Data obtained suggest that oligopeptides could be used to increase the tolerance to ethanol or to cure the negative acute effects of alcohol in motivated behaviours.     

Local blood flow in the emotiogenic structures of the brain in freely moving rats

The speed of local blood flow (SLBF) in positive emotiogenic hypothalamic zones was recorded in free-moving white rats, by the method of hydrogen clearance, in states of passive and active alertness, in conditions of artificial (local) activation (by cathode) and inactivation (by DC anode) and also during stimulation of other positive and negative emotiogenic structures. It was established that the natural or artificial activation of the emotiogenic brain zones elicits an increase of SLBF and the inactivation evokes its reduction. Blood flow of the positive emotiogenic brain zones is intensified by stimulation of other positive emotiogenic structures, is reduced by stimulation of the negative emotiogenic zones and does not change at stimulation of emotionally neutral zones. It is suggested, that the mechanism of vascular reactions elicited by activation of positive and negative emotiogenic brain structures has a neurogenic basis and is performed in the type of "axon-reflex" by collaterals of ascending and descending fibers of the forebrain medial bundle.     

Substance P in the central mechanism of the rabbit feeding response evoked by stimulation of the lateral hypothalamus

The effects of substance P on the central mechanisms of food motivation elicited by electrical stimulation of the lateral hypothalamus were studied in chronic experiments on rabbits. Intravenous injection of substance P (30 micrograms/kg) brought about a dramatic reduction in the excitability of the "food center" in the hypothalamus, which returned to normal 45-60 minutes after injection. Higher concentrations of substance P provoked food behavior inversion up to the replacement of food motivation by avoidance behavior. Intravenous injections of substance P disturbed the relationships between the hippocamp, midbrain reticular formation and hypothalamus seen in health. This manifested in complete cessation of the inhibitory effects of the dorsal hippocamp and facilitating influences of the midbrain reticular formation on the excitability of the hypothalamic "food center". It is assumed that disorders of the central mechanisms of food motivation may arise from the effects produced by substance P directly on the central nervous system or on the brain via changes in the hormonal balance and responses of the autonomous nervous system.     

Effects of intraoral mechanoreceptor stimulation on reticular formation neurones, in the rabbit

The effects of intraoral mechanoreceptor stimulation on the firing rate of single neurones of the brain stem reticular formation (RF) were investigated in rabbits. 30% of RF neurones responded to periodontal mechanoreceptor stimulation; 16% to mucosal mechanoreceptor stimulation and 6% to both types of stimuli. Periodontal stimulation induced mainly inhibitory effects localized within the mesencephalic and rostral pontine RF. Among periodontal afferents incisors were the most widely represented. The effects of mucosal mechanoreceptor stimulation were predominant in the medullary and pontine RF and they were mainly excitatory. The present results support the hypothesis that brain stem RF neurones can be recruited into regulating mastication and biting also by stimulation of intraoral mechanoreceptors.     

Role of motivational excitations in the integrative activity of individual cerebral neurons

It has been shown that motivational excitation is a factor that changes the functional properties of brain single neurones. On the basis of ascending activating influences of the hypothalamic initiative centres, motivational excitation considerably changes convergent and discriminating properties of the cortical units. It is toward the cortical and subcortical neurones excitated by motivation that excitations evoked by reinforcing stimuli are directed. Under repetitive reinforcing action a certain trace is imprinted in the dynamic architecture of motivational excitation, which is the neuronal basis of the action result acceptor. The apparatus of the action result acceptor, formed after the precedence principle, is precisely the directing factor of the animals' purposeful activity.     

Antistress effects of diazepam and activation of the positive reinforcing system upon changes on corticosteroid excretion and lipid level after peripheral electric pain stimulation]

It was shown in experiments on rats that the reaction of self-stimulation (SS) decreased the enhanced level of 11-hydrohycorticosteroids (11-HCS) in the blood after electrical pain stimulation(EPS) of the feet. Diazepam (1 mg/kg) decreased the levels of 11-HCS and beta-lipoproteids and increased the level of phospholipids after self-stimulation and pain stimulation. Diazepam and preliminary electrical pain stimulation induced activation of self-stimulation. It is concluded that diazepam and the activation of the positive reinforcing system exert similar effects on 11-HCS excretion and lipid levels after pain stimulation.     

Functional features of the receptive fields of neurons of the posterior temporal cortex of the cat

Dynamic characteristics of the visual receptive fields (RF) of neurones in the postero-temporal cortical area (field 21) of alert cat were studied in prolonged repeated testings of RFs in the absence of influence controlled in the experiment. Significant fluctuations of RFs were found in the studied neurones--in changes of RFs form, their size and orientation and also in RF fragmentation, i.e. simultaneous and/or alternating appearance of separate zones (discharge centers) of RFs in the process of testing. It is suggested that plasticity and variability of neurones' RFs in time in this study are mainly due to modulating effects of extravisual structures, uncontrolled in the test,--to reticular inputs in particular.     

Site on inhibition of the spino-bulbo-spinal reflex on stimulation of the anterior lobe of the cerebellum.

The effect of stimulation of the anterior lobe (AL) of the cerebellum on spinobulbo-spinal (SBS) reflex activity evoked by somatic and splanchnic afferentation was studied in chloralose-anaesthetized cats. Unit activity synchronous with the SBS component of the efferent discharge was observed at the level of motoneurons, descending axons of the dorsolateral and ventral funiculi and neurones of the reticular formation (RF). Conditioning stimulation of the AL inhibited this unit activity. Reticular formation units influenced from the AL had direct contact with segmental structures; these results showed that disappearance of the SBS reflex during AL conditioning is associated with the depressant effect of the cerebellar cortex on the reticular formation.     

Mechanisms of sensory seizures: brain-stem neuronal response changes and convulsant drugs

Generalized convulsive seizures can be triggered by sensory stimuli in animals treated with subthreshold levels of convulsant drugs. The sensory responses of the brain-stem reticular formation (RF) are extensively enhanced before seizure initiation with bicuculline, strychnine, pentylenetetrazol, physostigmine, and several other convulsants. The responses of RF neurons are more greatly enhanced than other nonprimary neurons in the hippocampus, amygdala, and cortex. The action of systemically administered convulsants involves direct effects on reticular neurons, because RF response enhancement is also seen with iontophoresis. RF neuronal response enhancement does not appear to involve actions of convulsants on specific neurotransmitters, because agents that act on different transmitters enhance the responses of the same RF neuron when given sequentially. Anticonvulsant drugs reverse the effects of convulsants on reticular neurons. The convulsant-induced response enhancement in the RF may involve blockade of inhibitory postsynaptic potentials and/or threshold reduction, effects observed in vitro. RF neurons may be most susceptible to convulsant action because these agents block habituation and other mechanisms that normally restrict RF neuronal responsiveness. The massive synchronization of reticular neuronal firing by sensory stimuli may induce seizures by intense output over widespread RF projection pathways analogous to the afterdischarge seizures seen with electrical stimulation of the RF.     

Role of sensory signals in the development of cortical influences on hypothalamic structures]

Neuron discharges of the hypothalamic ventro-medial and posterior nuclei were registered in immobilized cats during electrical stimulation of the ipsi- and contralateral nerves of the brachial plexus, the 1st and the 2nd somatosensory regions (SI and SII) and the visual regions of the cortex and the reticular formation (RF) of the mesencephalon. A reversible cold block of the SI and SII failed to change the effect of the nerve stimulation. Stimulation of the postero-ventral thalamic nucleus did not change the initial activity of the hypothalamic neurons and gave rise to no neuron activity that appeared on stimulation of the SII. A conclusion was drawn that cortico-hypothalamic influences that appeared on stimulation of the nerves and the postero-ventral nucleus of the thalamus were pronounced weakly.     

Effect of reticular formation on hippocampal neurons (field CA1)

The reaction of field CA₁ hippocampal neurons to stimulation of the reticular formation (RF) with impulses of different frequencies was investigated in experiments on unanesthetized rabbits. The effect of electrical and sensory stimuli was compared and the effect of reticular stimulation on the sensory responses was determined. With an increase in the frequency of RF stimulation, the number of neurons of field CA₁ responding with inhibition of the activity increases. Multimodal neurons of the hippocampus depend on the reticular input to a greater degree than unimodal neurons. Neurons whose activity does not change in response to the effect of sensory stimuli also do not respond to stimulation of the RF. Neurons responding with inhibitory reactions to sensory stimulation show a higher correlation with the effects of RF stimulation than neurons with activation reactions and, especially those with "complex" responses to the effect of sensory stimuli. In a considerable number of hippocampal neurons the responses to sensory stimuli change in the course of 10–15 min after stimulation of the RF. The role of the RF in the organization of the reactions of hippocampal neurons is discussed.Division of Memory Problems, Institute of Biological Physics, Academy of Sciences of the USSR, Pushchino-on-Oke. Translated from Neirofiziologiya, Vol. 3, No. 3, pp. 227–235, May–June, 1971.     

Reticular structures in the cat brain involved in startle reflexes to somatic stimuli of various modalities

Characteristics and reticular mechanisms of two types of late reflex responses, namely startle reflexes evoked by weak (tactile) and strong (high-threshold electrical stimulation of nerves) stimulation, were studied in cats anesthetized with chloralose. The peripheral and central organization of these responses, described as "tactile" and "spino-bulbo-spinal" reflexes, were subjected to comparative analysis. Definite rostro-caudal differentiation of the reticular structures involved in the formation of reflexes of these types was discovered with the aid of destructive lesions of the brain-stem reticular formation (RF). Reflexes of the first type relay mainly at the level of the pontine RF, whereas those of the second type relay mainly at the level of the medullary RF. This result was confirmed by reversible blockade of RF by injection of small doses of sodium chloride and procaine solutions into it. The functional significance of this differentiation of RF is discussed in the context of its motor and sensory functions.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 17, No. 3, pp. 380–390, May–June, 1985.     

Glutamate decarboxylase and GABA transaminase activity in the mitochondrial fraction of the dog brain limbic system during postnatal development

Overall glutamate decarboxylase (GDCase) activity in the initial mitochondrial fraction of the limbic structure is found to be regionally different it increases from the moment of birth up to 1 year, the midbrain reticular formation (RF), where the enzyme activity in the mitochondrial decreases in pups aged 3 month and reincreases in 1 year old dogs being the exception. Overall GABA-transaminase (GABA-T-ase) activity reaches the "adult" level and is the highest: in the hypothalamic and hippocampal mitochondria on the 1st postnatal day; in the limbic cortex (l1 and l2 fields), amygdala and midbrain RF--on the 12-16th postnatal days. During the period from 12-16 postnatal days up to the age of 1 year GABA-T-ase activity in the dog limbic system decreases reliably.     

Relation between the dynamics of the extinction process and the initial rate of hypothalamic self-stimulation in the rabbit

In experiments on rabbits with electrodes chronically implanted in the lateral hypothalamus, dynamics was studied of extinction of self-stimulation reaction as a result of cancellation of intracerebral reinforcement. General dynamics of extinction of the unreinforced instrumental actions and behavioural manifestations of orienting-investigating reaction were revealed. It was found, that in 30% of rabbits, the orienting reaction appearing as a result of "discordance" between expected and actual afferentation is attended by a species-specific form of behaviour, expressed in the form of hind paws synergic strokes against the floor. It is suggested that these strokes may be a somatic expression of a negative emotional state of animals during self-stimulation extinction. The comparison of extinction dynamics with the level of self-stimulation background frequency showed a relative independence of the strength of drive towards getting positive emotions on motivational effects created by electric stimulation of the reinforcing brain structures.     

Association between Sjogren's Syndrome and Respiratory Failure: Put Airway,Interstitia, and Vessels Close Together: A National Cohort Study

Objectives

Few studies have evaluated the association between Sjogren''s syndrome (SS) and respiratory failure (RF). Thus, we conducted a retrospective national cohort study to investigate whether Sjogren''s syndrome (SS) increases the risk of respiratory failure (RF).

Methods

The cohort consisted of 4954 newly diagnosed patients with SS but without a previous diagnosis of RF, and 19816 patients as the comparison cohort from the catastrophic illnesses registry, obtained from the 2000–2005 period. All of the study participants were followed from the index date to December 31, 2011. We analyzed the association between the risk of RF and SS by using a Cox proportional hazards regression model, controlling for sex, age, and comorbidities.

Results

The overall incidence rate of RF showed a 3.21-fold increase in the SS cohort compared with the comparison cohort. The adjusted HR of RF was 3.04 for the SS cohort compared with the comparison cohort, after we adjusted for sex, age, and comorbidities. The HRs of RF for patients with primary SS and secondary SS compared with the comparison cohort were 2.99 and 3.93, respectively (P for trend <.001). The HRs of RF increased as the severity of SS increased, from 2.34 for those with no inpatient care experience to 5.15 for those with inpatient care experience (P for trend <.001).

Conclusion

This study indicates that clinical physicians should not only consider secondary SS but also primary SS as a critical factor that increases the risk of RF.     

Shift of the catecholamine levels at stimulation of the hypothalamic emotiogenic zones

Using models of electrical self-stimulation of the positive emotiogenic zones and stimulation of the negative emotiogenic zones of the hypothalamus in rats, we demonstrated that both these stimulations increase the noradrenaline level in the frontal cortex. This shows a nonspecific nature of activation of the dorsal noradrenergic bundle, resulting from motivational excitation. When the frequency of self-stimulation reaction remained stable, activation of the dorsal noradrenergic bundle was moderate, and at decay of the above reaction it returned to the control level. Behavior connected with activation of the motor functions was characterized by an increase in the dopamine and noradrenaline levels in the caudate nucleus. In theglobus pallidum, the dopamine content changed only under conditions of stimulation of the negative emotiogenic zones: these were an increase in the reaction of active avoidance and a decrease in passive avoidance.     

Adaptive changes in the evoked electrical activity of the rat brain while training it in a controlled experiment]

A programmed change of a certain phase of cortical EP to a photic flash was reinforced in an unrestrained chronically operated animal (a rat) in the course of an operant controlled experiment. A painful subcutaneous stimulation or stimulation of the emotionally positive zone of the lateral hypothalamus was used as a reinforcing agent. It has been shown that painful stimulation is a more effective reinforcing agent than brain stimulation. Synchronous recordings pointed to a distinct correlation of activity in some structures (field CA1 of the hippocampus) with that of the visual cortex, while in others the EP form characteristically changed at different stages of learning (thalamic reticular nucleus), and in still others, there were no EP changes (midbrain reticular formation) at any stage of learning.     

Vascular and noradrenalic reactions in the musculocutaneous bed during hypothalamic stimulation.

When electrical stimulation is applied to the ventromedial hypothalamic zone one observes an increase in systemic blood pressure. There also occur blood pressure variations in the isolated femoral circuit: two distinct phenomena were observed. The early event, being either an increase or a decrease in peripheral resistance, is directly related to the amount of noradrenaline produced locally. The late event is due to catecholamines arriving from the general circulation. Inhibition of local catecholamine release through the baroreceptor reflex and inhibition of ganglionic transmission by a large and sudden increase in adrenaline blood levels do influence the response in the isolated femoral circuit. Moreover the peripheral vasomotor tonus seems to be influenced by yet another mechanism, independent of local catecholamine release. This delicate mechanism depends on the balance between the degree of excitation of hypothalamic pressor (medial) and depressor (lateral) zones.