Effect of ethanol on excitatory and inhibitory processes in the visual cortex of rabbits undergoing learning

Subcutaneous ethanol injection to waking rabbits in a dose of 2-6 g/kg causes discoordination of movements, a decline in motor reactions to inhibitory and reinforced light flashes, and appearance of equalizing and paradoxical relations in the number of reactions to these stimuli. Under the influence of ethanol, activating and disinhibitory action of the pain reinforcement on neurones of the visual area temporarily weakens, while the disinhibitory influence of light flashes (CS) is preserved. Judging from the dynamics of phasic reactions to the inhibitory light flashes, the ethanol in a dose of 2-6 g/kg does not influence the inhibitory hyperpolarization processes in the cerebral cortex of rabbits. Tonic inhibition of the cortical unit activity temporarily intensifies after the ethanol injection.     

Synchronization dynamics in the neuronal work of the neocortex and hippocampus during learning before and after the administration of nootropics and narcotics

The basal difference in action of the studied drugs was that nootropics (phenybut in a dose of 40 mg/kg and pyracetam in a dose of 200-400 mg/kg) did not change the initial action of pain reinforcement on synchronism in responses of the cortical neurones of alert nonimmobilized rabbits by inhibitory type (coincidence of the presence and absence of impulse activity) towards its decrease, while narcotics of various types (ethanol in a dose of 4-6 mg/kg, morphine-like opiate DAGO and opioid peptide DADLE in doses of 250 mkg/kg) eliminated the action of pain reinforcement on synchronism in responses of the cortical neurones both by inhibitory and activation (time of coincidence only of the presence of impulse activity) types. These and other drugs mainly weakened the initial action of both the inhibitory and reinforced light flashes of synchronism in neurones activity both by inhibitory and activation types. There was no constant parallelism between changes of synchronization and the frequency of the cortical impulses.     

Effect of a derivative of GABA, phenibut, on behavior and the activity of visual cortex neurons of the rabbit during elaboration of a defensive reflex and internal inhibition

In experiments on alert non-immobilized rabbits the effect of subcutaneous administration of the GABA-derivate--phenibut on behaviour, slow potentials and impulse activity of neurones of the visual cortex was studied during elaboration of a defensive reflex to light flashes and of conditioned inhibition. During the action of phenibut late negative-positive components of the evoked potentials to flashes, corresponding inhibitory pauses and postinhibitory activation gradually increased; then stable predominance of slow high-amplitude potential oscillations and corresponding neuronal group bursts appeared, separated by inhibitory pauses and in intersignal periods. Reinforcing stimulus, as before phenibut administration, lowered the amplitudes of slow potential oscillations and weakened inhibitory pauses in neuronal impulse activity. Dynamics of movements in response to the stimuli was of a phasic character. 3 hours after phenibut administration the discrimination of reinforced and inhibitory light flashes has distinctly improved. The obtained results confirm the initial concept of the significant role of the GABA-ergic inhibitory system in the process of elaboration of internal inhibition.     

Effect of substance P on behavior in the rabbit and the activity of cortical neurons during training

Subcutaneous injection of substance P to rabbits in a dose of 250 mcg/kg elicited a transitory disappearance of motor reactions to painful reinforcing stimuli and a reduction of their probability to reinforced and inhibitory light flashes, as well as a protracted heart rate increase and decrease of respiration rate. One third of the neurones recorded decreased their background firing level and or excitatory components of the reactions to reinforcement and conditioned light flashes. The decrease was most distinctly seen in the sensorimotor cortex and less pronounced in the visual cortical area and hippocampus. The influence of the substance P on different types of cortical inhibition was not the same. Tonic inhibition of neuronal activity in response to reinforcement was enhanced. Bioelectrical parameters which reflect an enhancement of inhibitory hyperpolarization during elaboration of internal inhibition (i.e. inhibitory firing delays and corresponding background and evoked slow potentials oscillations) were not changed.     

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.     

The dynamics of the activating and inhibitory types of cortical neuron synchronization during the realization of a defensive reflex and internal inhibition

In the visual and sensorimotor areas of the neocortex and in the hippocampus of alert nonimmobilized rabbits, in response to combinations of light flashes with electrocutaneous limb stimulation an increase was observed of synchronization in the activity of the near-by neurones by activation by inhibitory type (coincidence of the presence and absence of impulse activity). In response to flashes against the light background--conditioned inhibitor--in the visual cortex synchronization of neurones increased by inhibitory type, and in the sensorimotor cortex and hippocampus changes of synchronization appeared, similar to the action of pain reinforcement but considerably weaker. The increase of synchronization by the activation type took place mainly in the neurones pairs with unidirected increase of impulses frequency and by the inhibitory one--with its decrease. Along with this, in a considerable part of neurones pairs both changes of synchronization appeared at the impulses frequency changes of different direction.     

The response to monochromatic light flashes of the oxygen consumption of honeybee drone photoreceptors

Local measurements of the fall in oxygen pressure on stimulation of slices of the retina of the honeybee drone by flashes of light were made with oxygen microelectrodes and used to calculate the kinetics of the extra oxygen consumption (delta QO2) induced by each flash. The action spectrum for delta QO2 was obtained from response-intensity curves in response to brief (40 ms) monochromatic light flashes. The action spectrum of receptor potentials was obtained with the same experimental conditions. The two action spectra match closely: they deviate slightly from the photosensitivity spectrum of the drone rhodopsin (R). The deviation is thought to be due to wavelength-dependent light scattering and absorption in the preparation. In these experiments, the visual pigment was first illuminated with orange light, which is known to convert the bistable drone photopigment predominantly to the R state from the metarhodopsin (M) state. When long (300-900 ms) light flashes were used to elicit delta QO2, the responses to different wavelengths could not be matched in time course (as for the short flashes). Flashes producing large R-to-M conversions produced a prolonged delta QO2. The prolongation did not occur after double flashes, which produced both large R-to-M and M-to-R conversions. Similar changes in the length of afterpotentials in the photoreceptor cells and in a long-lasting decrease in photoreceptor intracellular K+ activity were found after long single or double flashes. The results are interpreted to show that the initial event for stimulation by light of metabolism in the drone retina is the same as that for stimulation of electrical responses (i.e., absorption of photons by R). Absorption of photons by M can produce an inhibitory effect on this stimulation.     

Effect of sodium nitrite on the activity of the neocortex neurons during realization of defense and inhibition conditioned reflexes

A decrease in intensity and duration of short-latency reaction components of the sensorimotor and visual cortical neurons to specific stimuli (pain reinforcement and light flashes, respectively) was observed after the administration of NO-generating sodium nitrite (11 mg/kg, subcutaneously). Activation decrease in the visual cortex took place irrespective of biological significance of the light flashes, i.e., in case when this stimulus was a signal of defensive conditioning and in case when these flashes were applied with continuous light (a conditioned inhibitor). Sodium nitrite almost did not change the late activation of sensorimotor and visual neurons in response to pain reinforcement and disinhibitory action of the latter. The results confirm the viewpoint about different neurotransmitters in "specifically modal" and "non-specific" pathways to the neocortex during learning.     

Adaptability of the receptive fields of neurons of the posterior temporal cortex and their sensitivity to parameters of photic stimulation in the cat

Study of receptive fields (RFs) of neurones in the postero-temporal cortex (field 21) of alert cat at three levels of visual adaptation: light photopic, light mesopic and practically dark or extremely low scotopic adaptations--revealed invariance of the most part of the studied RFs to the level of visual adaptation. Reorganization of RFs, connected with change of background luminosity were observed only in 12% of visually activated neurones. Significant reduction of responses to optic stimulation is shown at increase of the level of luminosity in 75% of neurones, revealing adaptive reorganizations. It is suggested that these reorganizations may take place in analogy with neurones of the field 17 on account of different involvement of intracortical inhibitory mechanisms (and, probably, not only in the postero-temporal cortex, but also in structures which precede it in visual hierarchy). Study of neurones sensitivity in the field 21 to parameters of optic stimulation revealed their considerable invariance to the length and orientation of the optic stimulus moving through the RF (60% of cases). Testing of RF by a rhombic optic stimulus did not change neuronal reactions, the form and dimensions of RF did not significantly change.     

The effect of acute alcoholization on the neuronal activity of the normal ventromedial hypothalamus and in pharmacological actions on the brain monoaminergic and opiate systems]

In experiments on white outbred male rats the specificity was studied of the influence and mechanisms of action of acute alcoholization (30%-solution of ethanol, intraperitoneally, 0.7 g/kg) on the activity of functionally different neurones of the ventromedial hypothalamus. Experimental results showed that the neurones, the activity of which lowered after saturation (I-st type), increased the discharges frequency at administration of ethanol. Nerve cells, the activity of which increased (II-nd type) and did not change (III-nd type) after saturation, had inhibitory character of reaction in response to alcoholization. The increase of serotonin content in the brain elicited by intraperitoneal administration of 5-OTPh (50 mg/kg) blockaded the action of ethanol on the nerve cells of the I-st type and did not change the effect of the alcohol on the neurones of the II-nd and III-nd types. Preliminary lowering of the noradrenaline level in the brain (disulphiram, intraperitoneally, 100 mg/kg) and blockade of opiate receptors (nalorphine, 5 mg/kg) fully eliminated ethanol influence on the activity of all types of neurones.     

Characteristics of the neuronal reaction of the substantia nigra to nociceptive stimulation

The nature of neurone response of substance nigra (SN) to nociceptive stimulation of the cat's peroneal nerve has been studied. The recording of neurone SN firing rate revealed that the majority (71.0%) of the SN neurones responded to the nociceptive repetitive stimulation of the peroneal nerve. But the thresholds of nociceptive activation in SN neurones turned to be very high. As a result of it the number of SN neurones responding to repetitive peroneal stimulation was twice as many as the number of cells responding to single stimulation of the nerve. The intravenous injection of naloxone in dose 1.0 mg/kg changed both excitatory and inhibitory responses in majority (71.4%) of SN neurones responding to repetitive peroneal stimulation. Naloxone did not modify the firing rate of neurones nonresponsive to nociception.     

Comparative study of interneuronal relations in the auditory cortex of awake and anesthetized cats

The character of interneuronal relations in the auditory cortex of alert and anaesthetized cats (nembutal) with chronicly inplanted electrodes was studied with the method of statistic analysis of cross-intervals of the two impulse series. The analysis of the histograms, obtained by means of processing a neuronal activity, showed that nembutal did not eliminate the dependent relations between neurones and that in the majority of cases the types of these relations are either retained or supplemented with new components. Experiments with a reduced dose of nembutal permitted to trace in time the changes in the amount of the inhibitory and excitatory interrelations in the anaesthetized state, and to compare these changes to the changes in the frequency of spike activity. It was found that nembutal predominantly suppresses the activity of the neurones, generating small spikes. The number of inhibitory connections is reduced simultaneously. Such synchroneity permits to assume the participation of the neurones generating small spikes in the establishment of inhibitory interrelations in the cat auditory cortex.     

Long-term changes in the activity of Purkinje cells and efferent cerebellar neurons following bilateral destruction of the inferior olive

The spontaneous discharge frequency of Purkinje cells and neurones of the cerebellar nuclei was evaluated in rats after complete bilateral destruction of their inferior olive with 3-acetylpyridine, performed one day to six months before. The deafferentation from the climbing fibers produced an increased inhibitory action of the Purkinje cells on their target neurones, lasting at least for one week. A relative compensation took place progressively during the first month, but the normal activity of the circuit did not recover even after six months.     

Microiontophoretic study of the effect of biogenic amines on unit activity in the rabbit visual cortex

The effect of acetylcholine, noradrenalin, and serotonin on spontaneous activity of visual cortical neurons and on their activity evoked by flashes, recorded extracellularly, was studied by microiontophoresis in unanesthetized rabbits. The ability of visual cortical neurons to respond to light does not correlate with their sensitivity to acetylcholine. This substance, which changes the spontaneous firing rate of many of the neurons tested, was less effective against their evoked activity. Noradrenalin had a powerful depressant action on both spontaneous and evoked activity of most neurons studied. Serotonin acted in different ways on the spontaneous and evoked activity of some neurons tested. It is postulated that acetylcholine mediates reticulo-cortical inputs, noradrenalin is a true inhibitory mediator in the cerebral cortex, and serotonin has a presynaptic action by preventing the liberation of natural mediators.     

Integrative mechanisms of the formation of the small intestine motor effects

Contractile responses of the small intestine to serotonine and histamine are mediated by cholinergic neurones, while the inhibitory responses of the substances--by nonadrenergic inhibitory neurones of the enterometasympathetic nervous system. An inhibitory response of the small intestine to met-enkephalin results from its depressing action on the effector cholinergic neurones. Catecholamines activate enteric cholinergic neurones via presynaptic beta-adrenoceptors and inhibit them via pre- and postsynaptic alpha-adrenoceptors. The cholinergic neurones of the enterometasympathetic nervous system seem to be under a double adrenergic control, and a mechanisms seems to exist in the small intestine for adrenergic activation of its contractile apparatus.     

Changes in the neuronal reactions of the substantia nigra to nociceptive stimuli during electroacupuncture

The nature of responses of neurones in substance nigra reticular (SNR) part of cats to nociceptive electrical stimulations and change of these responses under the action of electroacupuncture (EA) in the area corresponding to the Tsui-Sang-Li point in man have been studied. The most of the neurons studied (72.1%) responded to nociceptive stimulation either with excitation of inhibition of the impulsive activity. The EA eliminated or changed the effect of nociceptive stimulation in 73.2% of the SNR nociceptive responsive neurones. Intravenous naloxone administration blocked the effect of EA depending on a dose. A conclusion has been made that the SNR neurones are involved in the modulation of nociceptive transmission and that the EA action is directed to some restoration of the nociceptive disturbed balance between the excitatory and inhibitory processes in the SNR neuronal population.     

The roles of endogenous opioids in the inhibitory action of the hippocampus on preovulatory luteinizing hormone in rats

Whether endogenous opioid peptides were involved in the inhibitory action of the hippocampus (HPC) on luteinizing hormone (LH) release was studied examining the effect of naloxone, an opioid antagonist, on the inhibitory action of electrical stimulation of the HPC and also by examining the effect of metenkephalin administration in the HPC, on preovulatory release of LH in proestrous rats. In rats treated with saline at 13:00 h, either sham stimulation or electrical stimulation of the dorsal HPC, which was performed acutely under ether anesthesia, significantly inhibited the afternoon rise in serum LH. In animals treated with naloxone at a dose of 2.0 mg/kg body weight, the afternoon rise in LH appeared smaller than that in the control group. However, statistical analysis showed no significant difference in LH values compared to the control group. Direct administration of met-enkephalin at a dose of 10 micrograms at 13:00 h through a chronically implanted cannula in the HPC did not induce any significant change in the afternoon rise in LH, regardless of whether it induced behavioral seizures or not. The results suggest that opioid peptides in the HPC do not play a significant role in the inhibitory action of HPC on LH release. Opioids existing in areas other than the HPC may play a certain, but small role.     

Effect of dalargin on the processes of memory and learning in the rat

In experiments on rats, the influence was studied of dalargin on the elaboration and preservation of various homogeneous and heterogeneous conditioned reflexes (CRs) elaborated in single and multiple pairings. The effect of dalargin on the processes of learning and memory was compared with the action of the peptide on the activity of hypothalamic neurones. Administration of dalargin delayed the elaboration of maze defensive CRs and practically did not affect the elaboration of two-way avoidance. The preservation of CR also deteriorated under the influence of dalargin. Administration of dalargin 10 min before the CRs testing did not prevent their reproduction. When using CRs elaborated in a single pairing, dalargin disturbed the preservation of the drinking CR and improved that of passive avoidance CR. Dalargin in this dose affected the emotional state of animals in the open field and did not significantly affect their motor activity. Dalargin suppressed impulse activity in 17 out of 22 tested neurones of the lateral hypothalamus, with maximum effect in 20-50 min after its administration. The obtained data show that the character of dalargin action on the elaboration of CR and mainly on its consolidation, depends on the character of the elaborated CR and is probably due to great extent to the effect of the peptide on the brain emotional mechanisms.     

Fast visuomotor processing of redundant targets: the role of the right temporo-parietal junction

Parallel processing of multiple sensory stimuli is critical for efficient, successful interaction with the environment. An experimental approach to studying parallel processing in sensorimotor integration is to examine reaction times to multiple copies of the same stimulus. Reaction times to bilateral copies of light flashes are faster than to single, unilateral light flashes. These faster responses may be due to 'statistical facilitation' between independent processing streams engaged by the two copies of the light flash. On some trials, however, reaction times are faster than predicted by statistical facilitation. This indicates that a neural 'coactivation' of the two processing streams must have occurred. Here we use fMRI to investigate the neural locus of this coactivation. Subjects responded manually to the detection of unilateral light flashes presented to the left or right visual hemifield, and to the detection of bilateral light flashes. We compared the bilateral trials where subjects' reaction times exceeded the limit predicted by statistical facilitation to bilateral trials that did not exceed the limit. Activity in the right temporo-parietal junction was higher in those bilateral trials that showed coactivation than in those that did not. These results suggest the neural coactivation observed in visuomotor integration occurs at a cognitive rather than sensory or motor stage of processing.     

Effects of transections and electrical coagulations in the medulla oblongata upon the activities in the respiratory muscles of the crucian carp (author's transl)]

The following conclusions may be drawn from the results in this work. The respiratory cycles are formed by the neuronal machinery in the reticular formation under the posterior part of the vagal motor nucleus. The motor neurones or the neuronal networks composing the motor nucleus of the respiratory muscles tonically discharge the action potentials, when the neurones or the networks are released from the inhibitory influences of the interneurones connecting the neuronal machinery to the motor neurones. Furthermore, the interneurones probably generate the tonic discharges after removing the inhibitory influences of the other interneurones or the neuronal machinery on them. A reflex mouth closing is elicited by a mechanical stimulus applying on the upper lip. The motor neurones of the m. adductor mandibulae are activated via only one synapse in the reflex. The reflex action potentials recorded from the motor nerve reduce in amplitude at the resting phase of the nerve in the respiratory cycles. These results suggest that the respiratory motor neurones are by nature spontaneous generators of the tonic action potentials and, in the time of the normal breathing, the tonic activity is interrupted by an inhibitory influence of the neuronal machinery generating the respiratory cycles.