Age-related dynamics of thalamic-cortical evoked potentials in the rabbit in the early period of life

Data have been obtained on development of evoked potentials in the sensorimotor cortex to electrical stimulation of the thalamic ventroposterolateral nucleus (VPL) in rabbits in early ontogeny. In 3-5 days rabbits, under four times increase of threshold electric stimulation of VPL the thalamocortical response (TCR) is presented by a positive-negative potential with a long latency and minimum amplitude parameters. Second and third TCR positive components to increasing of threshold value of electric stimulation 4 times, are differentiated from 7-8 days age. Age dynamics of TCR amplitude-temporal parameters is characterized by a shortening of latency and an increase of oscillations amplitude, most expressed at 2-3 weeks of postnatal life. TCR of one month rabbit to increased threshold electrical stimulation of VPL is presented by short-latency positive-negative oscillation with a positive phase consisting of three components with successively increasing amplitudes.     

Dose-dependent tazepam modulation of amplitude-temporal characteristics of thalamocortical responses and the constant potential of the sensorimotor cortex in rabbits at eye opening

The pronounced benzodiazepine (antiphobic) modulation of the amplitude-temporal parameters of different components of the thalamocortical responses (TCR) of the sensorimotor cortex is observed in rabbits in their early postnatal ontogeny. This modulation is of a dose-dependent character and is registered not after the injection of tazepam in a concentration of the "therapeutic tranquilizing window" but also in the psychotoxic plasma range. A gradual increase in blood tazepam concentration in a young rabbit pup is accompanied by the wave-like and differential decrease in the amplitude of the second and third positive (P2 and P3) and third negative (N3) TCR components, while the second negative (N2) and fourth positive (P4) components tend to a wave-like increase. The dose-dependent dynamics of tazepam modulation of the P2, P3, and N3 latencies is characterized by a wave-like and differential increase. The latency of P4 decreases slightly and that of the N2 increases with a low degree of significance. The selective dynamics of benzodiazepine modulation appears to be related with peculiarities of the electrogenesis of each of the components. The dose-dependent modulation of the level of cortical DC potential is of the same character as the respective amplitude changes in P2, P3, and N3, but its fluctiatuons are more pronounced.     

A layer-by-layer analysis of the components of the thalamocortical responses of the rabbit sensorimotor cortex in ontogeny]

The data obtained in the paper showed that complex dynamics of changes of spatial-temporary situation of heterocomponent thalamocortical responses (TCR) at passing the sensorimotor cortex (SMC) was conditioned by the properties of electrogenesis of each TCR component, age and frequency of stimulation of ventroposterolateral (VPL) thalamus nucleus transformation of electric profile of the second positive component (PC-2) of the TCR at passing SMC might testify to algebraic summation in this component of bioelectric processes of several generation sources (invertible and non-invertible PC-2). The revealed properties of ontogenetic dynamics of the bioelectric fields profiles of the third negative component (NC-3) of the TCR might be the consequence of the age stages of the development and change of embryonal mechanisms of electrogenesis of the definitive ones in extremely similar negativities.     

Specifics of post-theta modification of synaptic transmission in thalamo-cortical input of the rat's barrel cortex

The possibility of the development of either the long-term posttetanic potentiation or the depression of focal evoked potentials in identified columns of the barrel somatic cortex of unanaesthetized rats during stimulation of their specific thalamocortical afferent fibers was shown. Phase-dependent potentiation developed after burst tetanization with the frequency of theta rhythm at the negative phase of a theta wave, whereas the stimulation at the positive phase produced the depression. Potentiation after continuous tetanization was observed only at the optimal selection of stimuli amplitude and duration. Excessively intense tetanization more frequently caused the depression of tested responses probably due to the involvement of recurrent inhibition.     

The morphofunctional characteristics of the neurons in the sensorimotor cortex of old rabbits during the trace assimilation of rhythm]

Extracellular neuronal activity was recorded from 460 neurons from alert young (5-7 months), middle-aged (54-65 months) and old (66-85 months) rabbits. Trace rhythmic activity of sensorimotor cortical neurons was examined after long-lasting (10-20 min) rhythmic (0.5-2 Hz) electrocutaneous stimulation of the contralateral forelimb. Spectral analysis of spike activity showed age-related differences in capability of producing a rhythm of previous stimulation in spontaneous neuronal activity. In young animals propriate rhythmic fluctuations of firing rate appeared after the first or second sessions of stimulations (on the first experimental day), in middle-aged ones--after 2-4 sessions (on the second or third days); cortical neurons in old rabbits did not exhibit trace rhythmic activity. Significant morphological changes in glial and neuronal cells were observed in sensorimotor cortex of old rabbits. It is proposed that morphological deteriorations may be the reason of the impairement of trace processes during aging.     

Propofol suppresses synaptic responsiveness of somatosensory relay neurons to excitatory input by potentiating GABAA receptor chloride channels

Propofol is a widely used intravenous general anesthetic. Propofol-induced unconsciousness in humans is associated with inhibition of thalamic activity evoked by somatosensory stimuli. However, the cellular mechanisms underlying the effects of propofol in thalamic circuits are largely unknown. We investigated the influence of propofol on synaptic responsiveness of thalamocortical relay neurons in the ventrobasal complex (VB) to excitatory input in mouse brain slices, using both current- and voltage-clamp recording techniques. Excitatory responses including EPSP temporal summation and action potential firing were evoked in VB neurons by electrical stimulation of corticothalamic fibers or pharmacological activation of glutamate receptors. Propofol (0.6 – 3 μM) suppressed temporal summation and spike firing in a concentration-dependent manner. The thalamocortical suppression was accompanied by a marked decrease in both EPSP amplitude and input resistance, indicating that a shunting mechanism was involved. The propofol-mediated thalamocortical suppression could be blocked by a GABA_A receptor antagonist or chloride channel blocker, suggesting that postsynaptic GABA_A receptors in VB neurons were involved in the shunting inhibition. GABA_A receptor-mediated inhibitory postsynaptic currents (IPSCs) were evoked in VB neurons by electrical stimulation of the reticular thalamic nucleus. Propofol markedly increased amplitude, decay time, and charge transfer of GABA_A IPSCs. The results demonstrated that shunting inhibition of thalamic somatosensory relay neurons by propofol at clinically relevant concentrations is primarily mediated through the potentiation of the GABA_A receptor chloride channel-mediated conductance, and such inhibition may contribute to the impaired thalamic responses to sensory stimuli seen during propofol-induced anesthesia.     

Depression and/or potentiation of cortical responses after status epilepticus in immature rats

Lithium-pilocarpine status epilepticus (SE) resulted in delayed changes of single cortical interhemisperic (transcallosal) responses in immature rats. Low-frequency stimulation inducing depression and/or potentiation was studied to analyze possible dynamic changes in cortical responses. Status was elicited in 12-day-old (SE12) or 25-day-old (SE25) rats. Control siblings received saline instead of pilocarpine. Interhemispheric responses were elicited by stimulation of the sensorimotor region of the cerebral cortex 3, 6, 9, 13, or 26 days after status. A series of 5 biphasic pulses with intensity equal to twofold threshold were used for stimulation. The interval between pulses was 100, 125, 160, 200 or 300 ms, eight responses were always averaged. Peak amplitude of the first positive, first negative and second positive waves was measured and responses to the second, third, fourth and fifth pulse were compared with the first one. Animals after status epilepticus as well as lithium-paraldehyde controls exhibit a frequency depression at nearly all the intervals studied. An outlined increase of responses in SE rats in comparison with the controls three days after SE stayed just below the level of statistical significance. In addition, animals in the SE12 group exhibited potentiation of responses at this interval after SE. With longer intervals after SE, the relation between SE and control animals changed twice resulting in a tendency to lower amplitude of responses in SE than in control rats 26 days after SE. Rats in the SE25 group exhibited higher responses than controls 13 days after status, but this difference was not present at the longest interval after SE. Low-frequency stimulation did not reveal increased cortical excitability as a long-lasting consequence of status epilepticus induced in immature rats. In addition, the outlined differences between SE and control rats changed with the time after SE.     

Frequency potentiation in the neonatal rabbit hippocampus

The formation of properties of frequency potentiation in the entorhinal afferent pathway of the hippocampus was studied in unanesthetized rabbits aged from 1 to 15 days. In areas CA₁ and CA₃ of the dorsal hippocampus in newborn rabbits repetitive (1–20 Hz) electrical stimulation of the perforant path led to an increase in amplitude of the slow wave of the field potential by 20–100% compared with the control and to an increase in the probability of response discharges from the neurons from 0–0.5 in the control to 0.8–1.0 during tetanization. In rabbits aged 2–3 days potentiation was more marked at a frequency of 4–6 Hz, whereas depression of the responses developed rapidly to a higher frequency of stimulation. The frequency optimum of 4–15 Hz was established on the 5th day. Potentiation of the first component of the field potential was observed starting from the 8th–10th day of life. The experimental results show that the property of frequency potentiation in the cortical afferent connections of the hippocampus is found in rabbits actually at birth, and it acquires the adult form at the beginning of the second week of life.Brain Institute, Academy of Medical Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 11, No. 6, pp. 533–539, November–December, 1979.     

Effect of pentobarbital on thalamo- and hippocampocortical processes in rats

Experiments were carried out on 28 rats immobilized with d-tubocurarine. The effect of three successive doses of pentobarbital (PB--5, 15 and 40 mg.kg-1) on electrocorticographic manifestations (evoked responses, the rhythmic afterdischarge and barbiturate spindles, the self-sustained afterdischarge--SSAD) elicited by electrical stimulation of two thalamic nuclei with a different type of control projection and the hippocampus (CA3) was compared. We found no difference between the effect of PB on cortical electrographic manifestations elicited by stimulation of the dorsomedial part of the ventral nucleus (VDM) and the anterior lateral nucleus (LA) of the thalamus. Cortical responses elicited by stimulation of the hippocampus were heterogeneous and the effect of PB on them was smaller than on thalamocortical responses. Reduction of the hippocampocortical SSAD was likewise not significant until the deepest stage of barbiturate anaesthesia.     

Influence of phenytoin and valproate on thalamocortical evoked potentials and their paired-pulse potentiation.

The action of phenytoin and valproate on thalamocortical responses was studied in adult rats. Single responses were not influenced by either drug. Paired-pulse potentiation of the initial components (first positive and first negative) observed with intervals from 50 to 200 ms under control conditions was abolished by phenytoin (60 mg/kg i.p.) but only moderately influenced by valproate (400 mg/kg i.p.). Paired-pulse potentiation of thalamocortical phenomena cannot be put into connection with the generation of the spike-and-wave rhythm.     

Neurophysiological analysis of postnatal development of corticostriate connections in rabbits

Evoked potentials were recorded in the caudate nucleus of adult rabbits and young rabbits aged 2–30 days in response to stimulation of the ipsilateral motor cortex. The response of the caudate nucleus in the adult rabbit consisted of a positive-negative complex with latent period of 3–5 msec. Maximal amplitude of the response was observed in the dorsorostral region of the nucleus. As the recording electrode was inserted deeper, the amplitude of the response gradually decreased but without reversal of its polarity. Responses of the caudate nucleus to stimulation of the motor cortex were recorded as early as on the 3rd day after birth. These responses were indistinguishable in configuration from responses of the nucleus of adult rabbits. Their latent period was about 10 msec. Between the 16th and 20th day after birth the latent period of the response decreased considerably — from 9 to 5 msec, and by the 30th day of life it had reached its definitive value. With age the amplitude of the response increased but the threshold of stimulation decreased, The results indicate early functional maturation of connections of the motor cortex with the caudate nucleus and they agree with the results of morphological investigations of the structural development of the afferent systems of this nucleus.Brain Institute, Academy of Medical Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 14, No. 3, pp. 284–289, May–June, 1982.     

Effect of visual deprivation on evoked potentials in the visual cortex and superior colliculus in rabbits

Evoked potentials arising in the visual cortex and superior colliculus to stimulation of the collateral eye by single, paired, and repetitive flashes were recorded in rabbits reared in darkness or in normal illumination. The absence of significant change in the latent period and amplitudes of the first two components of the collicular responses and of the recovery cycle and response to repetitive stimulation in the light-deprived animals suggest that photic stimulation does not affect the normal functional development of the rabbit retinotectal system. However, functional deafferentation in the early postnatal period gives rise to serious disturbances of visual cortical function, as reflected in a marked decrease in amplitude of the primary response, lengthening of the recovery cycle, and narrowing of the range of rhythm-binding frequencies of flashes. These disturbances were reversible. The period of maximal sensitivity of the rabbit retinocortical system to visual deprivation begins at the end of the first month of postnatal life. The possible mechanisms lying at the basis of these functional disturbances in light-deprived animals are discussed.     

Formation of "caudate spindles" in the rabbit sensomotor cortex during ontogeny

Electrical activity of the sensomotor and visual areas of the neocortex during stimulation of the caudate nucleus was recorded in young rabbits aged 3–60 days and in adults. Single stimulation of the caudate nucleus was found to cause the appearance of characteristic bursts of spindle-like rhythmic activity ("caudate spindles"), described previously in cats and monkeys, in the adult rabbit cortex. The latent period of the caudate spindle was about 200 msec, its duration 1–3 sec, and the frequency of its oscillations of the order of 12 Hz. Caudate spindles were most marked in the sensomotor cortex of the ipsilateral hemisphere. In rabbits under 10 days old caudate spindles were not found even if the intensity of stimulation was increased many times. Starting from the age of 15 days bursts of rhythmic activity resembling caudate spindles, but with lower frequency (about 8 Hz), longer latent period (up to 350 msec), and also with a higher threshold, appeared in the sensomotor cortex. The definitive type of caudate spindles was established toward the end of the first month of postnatal life, corresponding to the time of formation and complication of conditioned-reflex activity in developing animals.Brain Institute, Academy of Medical Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 17, No. 1, pp. 11–15, March, 1985.     

Facts and reflections on thalamo cortical reverberation of impulses

Experiments on cats, either unanesthetized or anesthetized with various doses of pentobarbital, showed that the cortical rhythmic after-discharge ("slow after-activity"), which has been regarded as a manifestation of reverberation of impulses in thalamocortical circuits [17], consists of a burst of spontaneous "spindles" evoked by stimulation. This conclusion is supported by the following facts: Spontaneous "spindles" and the rhythmic after-discharge respond absolutely identically (disappear) to activation of the EEG and deepening of pentobarbital anesthesia. The absence of thalamocortical reverberation is also indicated by the preservation of a rhythmic after-discharge (to clicks), synchronous with the cortex, in the thalamic relay nucleus (the medial geniculate body) after cooling or after removal of its projection zone.     

Electrical activity of the visual cortex under conditions of altered monoamine levels in the brain of animals

In experiments on 8 rabbits and 12 rats changes in electrograms of the visual cortex of alert animals were studied under photic stimulation in conditions of pharmacological action on monoamine (MA) brain systems. After injection of MA precursors (5-oxitriptophane and d, 1-dioxiphenylalanine) following phenomena were observed: a) decrease of the amplitude of the averaged evoked potentials to rhythmic photic stimuli (1-20 imp. sec.-1); b) an enhancement of fast (15-25 Hz) oscillations in the cortical spontaneous electrical activity and weakening and modification of the effects of the blockader of synthesis of MA-alpha-methyl-dioxiphenylalanine. Under light stimulation potentiation of MA precursors effects was observed in the frequency spectra of electrocorticograms. In the same conditions the specificity of action of cathecholamines precursor was revealed in the form of an increase of power of rhythms of 5-7 Hz and it; decrease in 2-3 Hz. Possible mechanisms of the revealed phenomena are discussed.     

Modulation of pyramidal response in the rat sensorimotor cortex after combined stimulation of the lateral hypothalamus and the sensorimotor cortex

It was shown during experiments on unrestrained rats that rhythmic stimulation of the pyramidal tract produced a statistically significant increase in the functional activity of neuronal populations of the sensorimotor cortex, manifesting as potentiation of the primary, positive phase of pyramidal cortical response. Combined rhythmically matched stimulation of the pyramidal tract and of the lateral hypothalamus leads to statistically significant enhancement in potentiation of the positive phase of pyramidal cortical response compared with effects produced independently of hypothalamic involvement. When stimulation of the pyramidal tract and the lateral hypothalamus are combined with stimulation applied at the same periodicity to the sensorimotor cortex, a further statistically significant enhancement in potentiation of the positive phase of pyramidal cortical response is seen in addition to the potentiating effect produced by hypothalamic stimulation.Institute for Brain Research of the All-Union Scientific Center of Mental Health, Academy of Medical Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 18, No. 3, pp. 367–373, May–June, 1986.     

Functional development of hippocampal mossy fiber synapses in rabbits

The course of functional maturation with age of mossy fiber synapses on pyramidal cells in areas CA_3,4 of the dorsal hippocampus was investigated by extracellular recording of focal potentials and single unit responses of the hippocampus to electrical stimulation of the dentate fascia in waking, unimmobilized rabbits aged from 1 to 14 days. After the 4th day of postnatal life focal potentials appeared in response to single stimulation, in the form of a biphasic short-latency wave, characteristic of responses of the mature hippocampus, accompanied by spike discharges with a latent period of 3 to 10 msec and inhibitory responses of the hippocampal neurons. During the next 10 days the amplitude of the focal potentials increased from several hundred millivolts, with the sharpest increase observed from the 4th through the 7th days. In early age periods global and unitary responses were shown to be capable of frequency potentiation and also of short-term after-potentiation.Brain Institute, Academy of Medical Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 12, No. 3, pp. 246–254, May–June, 1980.     

Transient changes of cortical interhemispheric responses after repeated caffeine administration in immature rats

Repeated postnatal caffeine treatment of rat pups led to transient developmental changes in cortical epileptic afterdischarges. To know if physiological cortical functions are also affected transcallosal evoked potentials were studied. Rat pups of the Wistar strain were injected daily with caffeine (10 or 20 mg/kg s.c.) from postnatal day (P) 7 to P11, control siblings received saline. Cortical interhemispheric responses were tested at P12, 18, 25 and in young adult rats. Amplitude of initial monosynaptic components was evaluated in averaged responses. Single pulses as well as paired and frequency (five pulses) stimulations were used. Developmental rules - highest amplitude of responses in 25-day-old rats, potentiation with paired and frequency stimulation present since P18 - were confirmed. Caffeine-treated rats exhibited transient changes: single responses were augmented in P25 if high stimulation intensity was used, paired-pulse and frequency responses were higher in experimental than in control animals at P12, the opposite change was observed in 18- and more markedly in 25-day-old rats. No significant changes were found in adult animals, monosynaptic transcallosal responses represent a simple and robust system. The developmental profile of described changes did not exactly correspond to changes in epileptic afterdischarges supporting the possibility that afterdischarges did not arise from early monosynaptic components of responses. In spite of transient nature of changes they can reflect delayed or more probably modified brain development.     

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.