Evidence for an ascending inhibitory histaminergic pathway to the cerebral cortex.

Previous observations from our laboratory indicate that metiamide is a specific histamine antagonist in rat cerebral cortex. In view of the recent finding that histamine levels and L-histidine decarboxylase (EC 4.1.1.22) activity in cerebral cortex decrease following disruption of the ipsilateral medial forebrain bundle (MFB), the present investigation was undertaken to examine whether iontophoretically applied metiamide antagonizes the inhibition of deep cerebral cortical neurones produced by stimulation of the MFB. In rats anaesthetized with a mixture of methoxyflurane, nitrous oxide and oxygen, stimulation of the ipsilateral MFB or the cortical surface with iontophoretically applied histamine depressed the firing of cortical neurones. Metiamide antagonized the histamine-induced depression and reduced the duration of inhibition produced by MFB stimulation. However, it did not alter the inhibition induced by the cortical surface stimulation. These results indicate that a histaminergic pathway ascending through the MFB may inhibit rat cerebral cortical neurones.     

Functional significance of the serotoninergic influence on neuronal activity of the somatosensory cortex in 12-day-old kittens

Monoamines, which participate in synaptic transmission as transmitters, also accomplish the modulation of neuronal activity. The role of serotonin (5-hydroxytryptamine--5-HT) was investigated in 8 to 14-day-old kittens by means of iontophoretic application onto neurones of the somatosensory cerebral cortex. The most typical response was the inhibition of neuronal activity. Another type of reaction was generated by inhibitory interneurones. After the microiontophoretic application of 5-HT, the tonic response of cortical neurones to the stimulation of the sciatic nerve changed into a phasic response. It is being suggested that the application of 5-HT to cortical neurones increases the excitability of inhibitory neurones. Hence, the serotoninergic regulation of neuronal activity in the somatosensory cortex may be operational from the 11th to the 12th day of postnatal life in cats.     

Cholinergic regulation of the activity of somatosensory cortex neurons during early postnatal ontogeny of the cat

In 11-14 days kittens, about 20% of neurones in the somatosensory cortical zone react to stimulation of subpallidal region which is a source of cholinergic projections to the cerebral cortex. The effect of subpallidal region stimulation is reproduced in case of microiontophoretic acetylcholine application and blocked by atropine what points to its cholinergic nature. Cholinergic stimulation causes inhibition of the background and evoked activities of the cortical neurones while, as it is known, in adult cats, acetylcholine mainly stimulates a reaction of activation. It is postulated that in kittens at the end of the second week of postnatal development, cholinergic innervation of the cortex significantly differs from the definitive one by its quantitative and functional parameters.     

Trace rhythm recruitment by the neurons of the rabbit sensorimotor cortex in old age]

Spectral analysis (ACG and gSP) of the impulse activity of the neurones of the old rabbits sensorimotor cortex allowed to reveal a trace recruitment of the rhythm--CR analogue to time--in after-action f rhythmic stimulation. Connection was established between the number of presented series of periodic electrocutaneous stimulation and expressiveness of the trace rhythm recruitment depending on the animals age. Trace rhythm recruitment took place slower in old animals (54-56 months) than in young ones (up to 1 year), chiefly in 2-3 experimental days after 2-4 series of rhythmic stimulation and was preserved in a small percent of cases the next day after stimulation. In the background activity of a number of neurones an initial periodicity was discovered, which was intensified under the influence of stimulation by another frequency, or the initial rhythm was extinguished, and stimulation rhythm was reproduced. Periodical stimulation in very old animals (66-85 months) practically did not evoke plastic reconstructions of the cortical neurones. Under the influence of the stimulation a non-specific trace increase of the frequency of neurones background activity of the old animals was observed. The revealed characteristics of plastic neurones properties may testify to projected disturbances of mnestic processes at definite age stages of normal aging.     

A presynaptic component of the action of iontophoretically applied flurazepam on feline cortical neurones.

The effect of iontophoretically applied flurazepam on the spike activity of pericruciate cortical neurones of the cat was studied. Flurazepam increased cortical inhibition produced either by local electrical stimulation (which is known to release gamma-aminobutyric acid (GABA) or by iontophoretically applied GABA. Following intravenous treatment with thiosemicarbazide (a GABA-synthesis inhibitor), flurazepam still augmented the action of GABA but was much less effective on electrically evoked cortical inhibition. These findings suggest that part of the action of flurazepam on inhibitory cortical transmission might be at the presynaptic level.     

Does the destruction of the catecholaminergic neurons in newborn rat pups influence the modulatory function of the cholinergic system?]

On outbred ratlings aged 21-31 days the influence was studied of the destruction of catecholaminergic (CA) system on the reactions of the neurones of the cortical somatosensory zone, elicited by the stimulation of the ischiatic nerve and modulation of these reactions after stimulation of the basal nuclei area (the source of the neocortex cholinergic innervation) and acetylcholine (ACh) microiontophoretic application. It is shown that destruction of CA system in newborn ratlings increases the reactivity of the somatosensory cortical neurones in 21-31 days old animals to sensory stimulation; it does not influence the efficiency of modulating action of the cholinergic system of the forebrain and leads to the increase of modulating influence of the applicated ACh. It is postulated that as the result of perinatal destruction of CA brain system, in the neocortex a specific morpho-functional organization is formed of structures and processes at which the modulating function of the forebrain cholinergic system turns out, by quantitative criterion, at least, to be compensated.     

Effect of the enkephalin derivative DAGO on neuronal behavior and activity in the neocortex and hippocampus of rabbits during the acquisition of conditioned defense and inhibitory reflexes

After subcutaneous injection of 25 mkg/kg morphine-like opiate--DAGO a decrease was observed of probabilities of rabbits movements at light flashes--defensive reflex signal. The level of the background neuronal impulse activity became gradually lower in the sensorimotor cortex and the hippocampus and did not change in the visual cortex. Decrease and restoration of responses to the reinforcing stimulus (electrocutaneous limb stimulation) in all studied cortical zones proceeded in one direction while there were significant differences in dynamics of responses to inhibitory and reinforced light flashes depending on the studied cortical zone and biological significance of the stimulus. Appearance is discussed of particular characteristics of neurones systemic organization during learning at change of reinforcement properties under the influence of the studied substance, as well as similarity of some features of mechanisms of internal inhibition elaboration in a defensive situation and of properties of positive reinforcement.     

Formation of serotonin- and GABA-ergic mechanisms of synaptic transmission in the cat neocortex during early ontogenesis

In acute experiment on 5-20 days kittens, the reactions were studied of neurones in the cortical somatosensory zone to stimulation of the dorsal raphe nucleus (DRN) and application of serotonin, ethanolamine-O-sulphate and bicucullin. The identity is established of the effect of DRN stimulation and serotonin application eliciting inhibition of the background activity and appearance of inhibitory phases in response to sensory stimulation, beginning from the 10-12th day after birth. A suggestion is made about serotoninergic regulation of GABA-ergic interneurones' in young animals. The dynamics of GABA-ergic brain system formation has been studied. Specific sensitivity of neocortical neurones to GABA increased to the end of the second week of life--the period when modulating serotoninergic influences appear.     

Electrical activity in sympathetic fibres to hind limb muscles of the cat produced by hypothalamic stimulation

Electrical stimulation of the "Defence Area" of the hypothalamus in anaesthetized cats was accomplished by stereotaxic placement of bipolar stainless steel electrodes; the spinal cord was sectioned at L4. The muscle blood flow in one hind limb was recorded with an electromagnetic flowmeter. Increases of between 100% and 300% were observed during hypothalamic stimulation. Electroneurographic recordings from small nerve filaments supplying tibialis anterior muscle revealed two populations of neurones whose activity was abolished by lumbar sympathectomy. It appears that the increased blood flow in skeletal muscle during stimulation of the hypothalamic "Defence Area" is brought about by a simultaneous inhibition of vasoconstrictor activity and increase in cholinergic vasodilator discharge.     

Activity of bulbar respiratory neurones during cough and other respiratory tract reflexes in cats

Changes evoked by mechanical stimulation of the relevant parts of the respiratory tract in the activity of inspiratory and expiratory neurones in the ventral respiratory group of the medulla oblongata, and in pleural pressure and the diaphragmatic electromyogram, were determined during cough, sneeze and the aspiration and expiration reflexes in 17 anaesthetized (but not paralysed) cats. The results of 72 tests of elicitation of the given reflexes showed that: Compared with the control inspiration, both the mean and the maximum discharge frequency of spontaneously active inspiratory neurones rose during the inspiratory phase of cough, sneeze and the aspiration reflex. Regular recruitment of new inspiratory units was also observed in the inspiratory phase of cough and the aspiration reflex. Compared with the control expiration, both the mean and the maximum discharge frequency of spontaneously active expiratory neurones rose during the cough, sneeze and expiration reflex effort. Recruitment of latent expiratory neurones was always observed in the expulsive phase of the given respiratory processes. The recruitment of latent expiratory neurones was accompanied by reciprocal inhibition of the activity of inspiratory units and recruitment of latent inspiratory neurones by inhibition of the activity of expiratory units and recruitment of latent inspiratory neurones by inhibition of the activity of expiratory units. Regular recruitment of the same expiratory neurones in all expulsive respiratory processes, together with the similar incidence of inspiratory neurones in the inspiratory phase of sneeze and the aspiration reflex, indicates that they are "nonspecific" in character.     

The role of the thalamic ventrolateral nucleus in the cortical effect on the activity of vestibular neurons

Electrocoagulation of lateral vestibular nucleus (NVL) reduces inhibitory effect of the motor and somatosensory areas and enhances the inhibitory effect of limbic, vestibular, and orbital cortical areas. Facilitating effect was enhanced by electrostimulation of the motor area and reduced by the stimulation of other cortical areas. Following the coagulation of the NVL, the ascending afferent flow to the cortex seems to be reduced. This results in diminishing of the cortical neurones tone and readjusts the descending influences upon the NVL neurones activity.     

Relationship between level of vigilance and changes in the receptive fields of the cat visual cortex]

The activity of 118 neurones of the primary visual cortex (17th field) was studied in unanesthetized cats, immobilized with d-tubocurarine, in a state of calm wakefulness and in strained attention, alarm. The strained attention was elicited by an air-puff directed to the corner of the closed eye, not used for the photic stimulation. Considerable rearrangments of the receptive field of neurones (94%) were observed in the state of strained attention. In the majority of the studied cortical cells (75%) during 10-30 minutes the excitatory centres of their receptive fields became narrower while their inhibitory periphery widened; in the cells with the inhibitory centres of the receptive fields they were larger in 80% of the cases. It is shown that with dark, mesopic and scotopic adaptation the major characteristics of the changes in the receptive fields remain unaltered. It is assumed that these effects have a behavioural value for the organism, because the created rise in the level of alertness is accompanied by a sharpening of the receptive fields, i.e. by a greater ability to a fine analysis and recognition of visual images.     

Formation of plastic connections of the visual system during ontogenesis of the rabbit

Analysis of evoked potentials and unit activity in the visual cortical projection area of rabbits revealed a definite succession of forming of interneuronal connections in ontogeny. In early postnatal period, the neuronal reactions were characterized by stable responses with one excitatory phase corresponding to initially negative surface evoked potential. Similarity of reactions of neurones situated in the same vertical column was observed and explained by functioning of a system of rigid connections of the thalamic relay nuclei afferents with cortical pyramidal neurones. Beginning from the third week of postnatal life of rabbits the neuronal reactions assumed a distinctly expressed phasic character, and variability of responses was seen along the vertical line. The changes revealed correlated with formation of a system of interneurones providing a possibility of plastic neuronal interaction. A study of the influence of preliminary cortical stimulation of the associative areas showed that intercentral cooperation mediated by cortical interneurones providing a systemic analysis of visual information began to form from the third week of postnatal life and reached the definitive level at later stages of development.     

The interaction between dopamine D2-like and beta-adrenergic receptors in the prefrontal cortex is altered by mood-stabilizing agents

Several studies have suggested the involvement of biogenic monoaminergic neurotransmission in bipolar disorder and in the therapy for this disease. In this study, the effects of the mood-stabilizing drugs lithium, carbamazepine or valproate on the dopaminergic and adrenergic systems, particularly on D2-like and beta-adrenergic receptors, were studied both in cultured rat cortical neurones and in rat prefrontal cortex. In vitro and in vivo data showed that stimulation of beta-adrenergic receptors with isoproterenol increased cyclic adenosine monophosphate (cAMP) levels and this effect was significantly inhibited by lithium, carbamazepine or valproate. The activation of dopamine D2-like receptors with quinpirole decreased the isoproterenol-induced rise in cAMP in control conditions. This inhibition was observed in vivo after chronic treatment of the rats with carbamazepine or valproate, but not after treatment with lithium or in cultured rat cortical neurones after 48 h exposure to the three mood stabilizers. Dopamine D2 and beta1-adrenergic receptors were found to be co-localized in prefrontal cortical cells, as determined by immunohistochemistry, but western blot experiments revealed that receptor levels were differentially affected by treatment with the three mood stabilizers. These data show that mood stabilizers affect D2 receptor-mediated regulation of beta-adrenergic signalling and that each drug acts by a unique mechanism.     

The neurochemical basis of recurrent inhibition in the reflex arch of the defensive reaction]

Mechanisms of habituation in the network of identified neurones were investigated in isolated preparation of central nervous system in the snail Helix. It has been found that intracellularly induced spike discharge in premotor command neurones decreases synaptic responses to repeated nerve stimulation in all recorded command neurones. Application of the neuropeptide FMRFamide elicits similar changes in the network. Taking into account that the investigated command neurones contain FMRFamide, as was shown immunochemically, it is possible to assume the existence of recurrent inhibition in the network underlying avoidance reactions. This recurrent inhibition causes habituation of the network output in the cases when the repeated stimuli do not evoke sensitization via activation of serotonergic cells.     

Effect of GABA on a temporary connection in a neuronal population of the sensorimotor cortex in rabbits

Evoked activity of sensorimotor cortical neurones in response to stimulation of the pyramidal tract, medial lemniscus and reticular nucleus of the midbrain tegmentum; driving reaction of cortical neurones at stimulation of these brain structures of growing frequency, and conditioned reflexes elaborated by combination of direct stimulation of the sensorimotor cortex and electrocutaneous stimulation were studied in awake nonimmobilized rabbits. Application to the cortex of GABA solutions of low concentration (less than or equal to 1%) emphasizes the evoked neuronal responses, facilitates the appearance of driving reaction and contributes to the manifestation of the temporary connection. Application of GABA solutions of higher concentration (greater than 2%) leads to opposite effects. Positive correlation is found between electrical and behavioural phenomena. The described experimental approach may be used for analysis of various types of influences on temporary connection formation.     

Application of the simplified method of optic recording for mapping focuses of the neuronal activity in the somatosensory cortex of the white rats

In rats, a differential signal was used for evoking an optical image in the barrel-field zone which represented a difference between cortical images during the control and the stimulation periods. After a subtraction of averaged sequences of frames, an image of spots reflecting a probable location of activated groups of neurones was obtained. Natural low frequency stimulation of vibrissae is supposed to be the most effective. The method of intrinsic optical activity imaging can be applied for preliminary mapping of cortical zones.     

Changes in the configuration of conditioned reactions of visual cortex neurons during changes in reinforcement parameters]

In order to study the influences of controlled changes of defensive integration on the activity of visual cortical units their responses to a conditioned light flash and electric cutaneous stimulation with a 600 msec interval between them were recorded in experiments on alert rabbits. It has been shown that in a third of the neurones the types of reaction to light flashes and electric stimuli coincide. The changes in parameters of the reinforcing shock led to a changed response of most cells to the conditioned photic stimulus and electric stimulation. The changes may have affected units which produce any activation phase, including cells with activity characteristic of detectory ("simple" and "complex") visual neurones. The data obtained suggest that the special function of the visual cortex is used in different ways in systemic mechanisms of conditioned and unconditioned defensive acts and that the integrated system of a behavioral act exerts control both on the use of the unit in a certain systemic process and on its receptive field.     

No inhibitory effect on receptor neurone activity by sulphur analogues of the sex pheromone component (Z)-5-decenyl acetate in the turnip moth, Agrofis segetum (Lepidoptera: Noctuidae)

Abstract. Olfactory responses from the entire antenna and from single antennal sensilla of the male turnip moth, Agrotis segetum (Lepidoptea: Noctuidae Schiff.), were recorded after stimulation of the antenna with the sex pheromone component, (Z)-5-decenyl acetate (Z5-10:OAc), and three sulphur analogues of this compound. Adaptation of olfactory receptor neurones tuned to Z5-10:OAc was investigated after pre-exposure of these receptor neurones to the key stimulus and to the three sulphur analogues. Both electro-antennographic and single sensillum recordings revealed that the sulphur analogues had a significantly decreased effect compared to the natural stimulus. The pre-exposure experiments demonstrated that no further inhibition of neural activity was observed than could be expected from receptor neurone adaptation. Earlier reports, describing sulphur analogues as possible hyperagonists acting on moth pheromone receptor neurones, are not supported by the present study.     

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.