[Analyzing A- and 0-rhythms of Conditioned Avoidance Reflex in the Rat Brain With Granger Causality].

It has been shown by the method of frequency decomposition of conditional Granger causality that under the execution of conditioned avoidance reflex θ-rhythm from the ventral hippocampus concurrently influences the ventral tegmental area and the series-connected basolateral amygdala and medial prefrontal cortex. Under the expectation of conditioned signal δ-rhythm from the prefrontal cortex influ- ences the ventral tegmental area and the amygdala.

[Δ-, θ-Modulation of the Ventral Tegmental Area Fast-Gamma Activity in the Course of Performance of Conditioned Avoidance Reflex in Rat].

The prestimulus expectation period of conditioned avoidance reflex features synchronized Δ-rhythm (1-4 Hz) in the medial prefrontal cortex and the ventral tegmental area (VTA), and synchronized θ-rhythm (6-8 Hz) in the above-mentioned structures and the hippocampus. According to "Granger causality" Δ- and θ-rhythms flow (are predictors) in the direction from the prefrontal cortex and the hippocampus to the VTA. Performance of conditioned avoidance reflex was marked by Δ-rhythm elimination simultaneously with generation of high-frequency (8-11 Hz) synchronized θ-rhythm. Δ-rhythm was shifted from the pre- to poststimulus period and prefrontal cortex--VTA θ-synchrony was eliminated in the cases of mistaken reaction withdrawal, Pavlovian fear conditioning scheme, conditioned signal presentation in the safe chamber part. The phase of Δ-, θ-rhythm modulates the amplitude of VTA fast (70-160 Hz) γ-activity envelope, VTA/cortex and VTA/hippocampus γ-phase synchronization and phase lag indexes, and frequency of simultaneously recorded VTA neuronal activity.

[The Interaction of the Medial Prefrontal Cortex, Ventral Hippocampus and Basolateral Amygdala in the Course of Performance of Conditioned Avoidance Reflex].

The interaction (synchronization) of activity of the medial prefrontal cortex, hippocampus and basolateral amygdala have been studied in the course of performance of conditioned avoidance reflex. The pre-stimulus expectation period was characterized by low-frequency delta-activity (1-4 Hz) with the source (according to criteria of Granger causality) in the prefrontal cortex and also by synchronized theta-rhythm (6-8 Hz) in the hippocampus. The performance of conditioned avoidance reflex was characterized by generation of high-frequency synchronized theta-rhythm (8-11 Hz) simultaneously with delta-activity elimination. The phase of delta- (theta-) activity modulates the envelope of gamma-rhythm (~30-120 Hz) in each of the structures. The elaboration and strengthening of conditioned reflex leads to concurrent theta power and synchronization growth in relation to reflex performance, but not during the prestimulus expectation period.

[Long-term potentiation and oscillation synchrony in the-ventral hippocampal-prefrontal pathways].

The results of the present study show the augmentation of hippocampal-cortical coherence and phase synchronization in theta-frequency and wider (1-15 Hz) low frequency range, during the time-period of LTP of monosynaptic prefrontal cortex focal potentials. The augmentation was detectable only in that activity segments with low to near-zero hippocampal theta frequency power. No definite changes in amplitude correlation of theta-rhytm envelops has been established.

The effects of systemic administration of selective antagonists of dopamine D1 and D2/D3 receptors on food-related and defensive (escape responses) conditioned paw-placing responses in cats.

Experiments were performed on cats to study the effects of systemic administration of antagonists of dopaminergic transmission on food-related and defensive (an escape response) operant conditioned reflexes acquired on the basis of the innate response of placing the forepaw on a support. Selective blockade of D1 receptors with SCH23390 (0.005-0.1 mg/kg) completely and selective blockade of D2/D3 receptors with raclopride (0.1-0.25 mg/kg) partially suppressed both reflexes. At these doses, both blockers had stronger actions on the defensive conditioned escape reflex than the food-related reflex: SCH23390 had significantly stronger inhibitory effects on both reflexes than raclopride.

The appearance of long-latency responses to a conditioned signal in the cortex is explained by strengthening of collateral connections between pyramidal neurons.

Experimental analysis and computer simulation of the neurophysiological processes underlying the "stable and local electrophysiological expression of conditioned reflexes" in the cerebral cortex, a phenomenon discovered in Asratyan's laboratory in the 1960s, showed that the long-latency components of cortical evoked potentials to a conditioned signal correspond to the late phases of the responses of motor cortex neurons, which are analogous to and probably generated by the same mechanism as long-latency epileptiform reactions of neurons in the epileptogenic cortex. Late long-latency components are generated via activation of NMDA receptors in the collateral connections between pyramidal neurons. The delay in the generation of responses depends on the initial activation of GABA(A) receptors and the slow kinetics of the current through NMDA channels. The appearance of late components as a result of training is explained by increases in the efficiency of collateral excitatory connections between pyramidal neurons.

[Long-latency responses to conditioned stimulus in the cat motor cortex can be generated through the enhancement of efficiency excitatory collaterals of pyramidal neuron]. / Poiavlenie dlinnolatentnykh otvetov na uslovnyi signoal v kore, ob"iasniaetsia usileniem kollateral'nykh sviazei mezhdu piramidnymi neironami.

The long-latency excitatory components are the characteristic feature of neuronal responses to conditional stimuli in the motor cortex of the cat. The data presented suggest that the neuronal machine that generates these reactions is that, generating long-latency epileptiform discharges in epileptogenic cortex. The long-latency component generation is based on NMDA-receptor activation in the recurrent excitatory collaterals of the cortical pyramidal neurons. The response delay is dependent on initial activation of inhibitory GABA(A) receptors. The emergence of the late components in the course of motor learning take place as a result of efficiency enhancement of recurrent collaterals synaptic linkage with pyramidal neurons.

[Structure and expression of the F6.2 gene in Chironomus thummi and other Chironomus species]. / Struktura i ékspressiia gena F6.2 u Chironomus thummi i drugikh vidov roda Chironomus.

A full-length copy of the F6.2 gene from the tissue-specific BRa locus of the Chironomus thummi chromosome IV was isolated and analyzed. The gene contains two exons (715 and 644 bp, respectively) and one 172-bp intron. The data of the RT-PCR analysis demonstrated that F6.2 was transcriptionally active at different developmental stages of Chironomus thummi and at least in the last larval stage of C. dorsalis. The distribution of the F6.2 gene among 42 species of Chironomus, as well as among two other genera of the family Chironomidae was examined by means of PCR. The F6.2 sequence was found in 34 Chironomus species. Using in situ hybridization, three species were analyzed for the presence of the F6.2 homologous sequences. In five species, the sequence of the F6.2 PCR product was determined. In these species, the intron size polymorphism caused by the variation of the number of the intron-forming repeats was observed. The data obtained provided evaluation of the F6.2 distribution among the genus Chironomus.

A computer model of neural processes observed in the cat motor cortex during performance of an operant movement.

This report describes a computer model of a "column" in the cat motor cortex. The model includes two layers of two-segment pyramidal neurons with two groups of inhibitory interneurons in each layer, which selectively control the somatic and dendritic segments of the pyramidal cells. In this model, neurons include active sodium, calcium, and several types of potassium currents. Excitatory connections between neurons are of the AMPA and NMDA types, while collateral connections between neurons of the upper layer are mainly of the NMDA type; connections between neurons in the lower layer are of the AMPA type. All inhibitory connections are of the GABA(A) type. The model reproduces the main neuronal processes seen in the cat motor cortex during performance of an operant movement. Pyramidal neurons of the upper layer generate primary and secondary responses to external stimuli. As in real experiments, secondary NMDA-dependent responses appear when GABA(A) inhibition is weakened and disappear when stimulation is increased; these properties of secondary responses are only reproduced when NMDA receptors are located in the terminals of collateral connections. Using only rapid NMDA-independent connections, neurons in the lower layer generate a slow bell-shaped wave of excitation (a "motor command"), which is formed by sequential activation of neurons with dendritic trees of different sizes.

NMDA-dependent and NMDA-independent neural processes in the bicucculline-disinhibited motor cortex of the cat during the acquisition and reproduction of a conditioned paw-on-support placing reflex.

Neuron activity was recorded in the motor area of the cat cortex during acquisition of an operant conditioned reflex consisting of placing the forepaw on a support in conditions of local disinhibition by spontaneous diffusion of the GABA(A) receptor blocker bicucculline from the recording micropipette. The conditioned signal was electrical stimulation of the parietal cortex with a train of 3-5 impulses. Addition of 2-amino-5-phosphopentanoic acid (APV), an NMDA glutamate receptor blocker, led to disappearance of the secondary excitatory components (in the poststimulus interval 30-120 msec) from neuronal responses in the disinhibited cortex both to the "indifferent" (before training) and the conditioned stimulation of the parietal cortex, while excitatory reactions associated with elevation and placing of the paw on the support showed no significant change in the presence of APV. Acquisition of the operant conditioned reflex was accompanied by an increase in the amplitude (p < 0.006) and duration (p < 0.00002) of secondary responses and decreases in their latent periods (p < 0.00002). In some cases--in fixed conditioned reflexes--secondary responses to conditioned stimulation in the disinhibited cortex were transformed into trains of epileptiform discharges. The hypothesis that changes in neuronal reactions in the disinhibited cortex during learning are based on increases in the efficiency of horizontal (collateral) connections between pyramidal neurons in layers II and III of the cortex is discussed.

[Local disinhibition with bicuculline does not break the trained relationship between afferent input and efferent output in cat motor cortex]. / Lokal'noe rastormazhivanie bikukullinom ne narushaet vyrabotannoi koordinatsii mezhdu taktil'nym vkhodom i dvigatel'nym vykhodom v dvigatel'noi kore koshki.

Neurons of the cat motor cortex related to the lifting-withdrawal phase of forepaw placing reaction are preferentially activated by tactile stimulation of the dorsal surface of the forepaw. The placing reaction was altered in such a way that the innate "dorsal placing" was subjected to extinction and was substituted for the newly acquired conditioned reaction in response to the ventral side stimulation. This alteration of placing reaction led to the inversion of the innate input-output relationship in the motor cortex. The neurons related to forepaw lifting-withdrawal began to be activated by tactile stimulation of the ventral rather than dorsal forepaw surface. Local cortical disinhibition by bicuculline application at the recording site qualitatively changed neither normal input-output relationships nor inverse relationships after placing reaction alteration. This suggests that alteration of the sensorimotor coordination in cat motor cortex is underlain by changes in excitatory rather than inhibitory connections.

[The blockade of D1 dopamine receptors in cat motor cortex causing an increase in the latency of conditioned forelimb placing reaction]. / Blokada D1-retseptorov dofamina v dvigatel'noi kore koshki vyzyvaet uvelichenie latentnogo perioda uslovnogo refleksa postanovki perednei lapy na oporu.

Cat were trained to place a forepaw on a support in response to touching the ventral surface of the forepaw as a conditioned stimulus. A selective D1 receptor antagonist SCH23390 was injected under pressure into the region of pericruciate cortex just anterior and lateral to the end of the cruciate sulcus. Electrical microstimulation of this region evoked the elbow flexion and shoulder withdrawal that constitute the initial lifting--withdrawal phase of the forepaw placing. In contrast to control saline, the injection of SCH23390 caused a gradual increase in the latency of conditioned placing so that to the end of experiment it was, on the average, 200 ms longer than its preinjection level. The results obtained show that the local D1 receptor blockade in cat motor cortex significantly increases the latency of the simple instrumental conditioned reflex.

[A computer model of generation of the motor cortex neuron processes seen in the course of execution of instrumental movement]. / Komp'iuternaia model' neironnykh protsessov, nabliudaemykh v dvigatel'noi kore koshki pri vypolnenii instrumental'nogo dvizheniia.

A computer model of neuronal processes in the motor cortex column is presented. The model is consisted of two pyramidal cell layers with two groups of inhibitory interneurons, selectively controlling pyramidal cell soma and dendrite, in each. Active Na, Ca and K conductances are included in the model of a single neuron. Horizontal excitatory connections between pyramidal cells in the upper layer are largely of NMDA-receptor type, that in the lower layer--of non-NMDA-type. All inhibitory synapses are of GABA(A)-type. The model reproduces the main phenomenon observed in the motor cortex during the execution of conditioned movements. Consequent to an early excitation the upper layer pyramidal cells generate a late NMDA-dependent reflexive response to afferent conditional stimulation, which as in a real case is diminished by GABA(A)-type synaptic inhibition and afferent stimulus strength increase. The characteristic inverse relation between the late response manifestation and the stimulus strength observed in the real cortex can be reproduced in the model only if NMDA-glutamate receptors were preferentially localized in the terminals of pyramidal cell backward collaterals, not in the terminals of the afferent fibers on pyramidal neurons. The intended component of motor cortex neuronal activity is generated in NMDA-independent manner by the pyramidal cells of lower layer. The slow time coarse of intended component as compared with short duration of AMPA epsp's is due to a consecutive relay-race--like activation of pyramidal neurons with different dendrit-to-soma ratio.

[NMDA-dependent and NMDA-independent neuronal processes in the cat motor cortex, disinhibited by bicuculline, during forepaw placement conditioning]. / NMDA-zavisimye i NMDA-nezavisimye neironnye protsessy v dvigatel'nom kore koshki, rastormozhennoi bikukullinom, pri vyrabotke i vosproizvedenii uslovnogo refleksa postanovki lapy na oporu.

Neuronal activity associated with a conditioned forepaw placing reaction was recorded in the cat's motor cortex locally disinhibited by bicuculline spontaneously diffused from the recording pipette. Electrical stimulation of the parieral cortex (area 5) with 3-5 pulses was used as a conditioned stimulus. In both naive and trained cats, adding of APV (NMDA receptor blocker) led to disappearance of the late (30-120 ms) secondary excitatory responses from the pattern of the neuronal reaction to the parietal stimulation recorded in the motor cortex. At the same time, the APV administration did not change the excitatory reactions (recorded, predominantly, in the deep cortical layers) time-locked to the execution of the conditioned movement. The conditioning resulted in a statistically significant increase in the amplitude and duration of the late secondary responses as well as in a shortening of their latency. In some cases (after a long period of training), the late secondary responses to the conditioned stimulus transformed into paroxysmal epileptiform bursts. A hypothesis is discussed that the increase in synaptic strength of the backward horizontal collaterals of layer-II/III pyramidal neurons is responsible for the learning-related changes in the neuronal reactions in the disinhibited motor cortex.

Long-term potentiation of the late NMDA-dependent components of neuron responses in the cat motor cortex to stimulation of the direct cortical input from field 5 of the parietal cortex.

Bicuculline-filled microelectrodes were used to record responses to weak stimulation of the parietal cortex in field 5 of the motor cortex of anesthetized cats, and revealed late excitatory responses of neurons similar to those seen in the motor cortex of conscious cats in response to conditioned stimulation of the parietal cortex triggering a conditioned reflex consisting of placing the paw on a support. Tetanic stimulation of the parietal cortex (10-20 sec, 100 Hz) in the same conditions evoked long-term potentiation of late responses, resulting in the formation and enhancement of responses, along with decreases in the latent period of responses.

[The late excitatory responses of the motor cortex neurons in the cat to stimulation of the pyramidal tract]. / Pozdnye vozbuditel'nye otvety neironov dvigatel'noi kory koshki na razdrazhenie piramidnogo trakta.

Under conditions of partial suppression of GAMKA-dependent cortical inhibition in the motor cortex of anesthetized cats, a weak electrical stimulation of the pyramidal tract evoked the late slow (50-200 ms) excitatory reactions in the motor cortex neurons similar to those previously recorded under the same conditions in response to stimulation of the parietal cortex. This finding favors the proposal that the late excitatory component of the cortico-cortical response reflects the repetitive activation of cortical neurons due to excitation spread via the system of cortical recurrent excitatory collaterals.