Intracortical synchronization of the epileptiform field potentials at different stages of ultrastructural reorganizations in neuronally isolates island in rats

A temporal delay (parameter of synchronization) between the incidence of epileptiform discharges in cortical sited located at a distance of 4 mm from each other was studied in rat intact cortex and neuronally isolated cortical slab using the cross-correlation function. Experiments were carried out at different stages of axonal sprouting. By 30 days of isolation, a significant increase in the number of boutons in the V cortical layer coincided with a significant decrease in the delay, whereas a reduction of the number of boutons by 90 days corresponded to its increase. These findings convincingly testify that the newly formed boutons form a basis for increase in synchronization and thus affect the epileptogenesis. The results obtained in this work and literature data suggest that under pathological conditions large pyramids of the V layer form a neuronal network which provides exclusively cortical synchronization of epileptiform field potentials.     

Character of neuronal functional associations according to the content of RNA and SH-groups in the cat cerebral cortex]

A new principle of taxonomy was used for determination of the spaceal character of the neuron cortex associations based on RNA and SH-group contents. The experiments were performed on the intact cat's somatosensory cortex, and after epileptiform activity induced by electrical stimulation. In the intact cortex, the neuronal mosaic of metabolic activity (determined by RNA and SH-group contents) was meshed, whereas in the hemisphere with epileptiform activity this mosaic was formed by less numerous but larger groups of cells. The functional significance of these groups is discussed.     

Spiking behavior and epileptiform oscillations in a discrete model of cortical neural networks

Summary We investigate the phenomenon of epileptiform activity using a discrete model of cortical neural networks. Our model is reduced to the elementary features of neurons and assumes simplified dynamics of action potentials and postsynaptic potentials. The discrete model provides a comparably high simulation speed which allows the rendering of phase diagrams and simulations of large neural networks in reasonable time. Further the reduction to the basic features of neurons provides insight into the essentials of a possible mechanism of epilepsy. Our computer simulations suggest that the detailed dynamics of postsynaptic and action potentials are not indispensable for obtaining epileptiform behavior on the system level. The simulation results of autonomously evolving networks exhibit a regime in which the network dynamics spontaneously switch between fluctuating and oscillating behavior and produce isolated network spikes without external stimulation. Inhibitory neurons have been found to play an important part in the synchronization of neural firing: an increased number of synapses established by inhibitory neurons onto other neurons induces a transition to the spiking regime. A decreased frequency accompanying the hypersynchronous population activity has only occurred with slow inhibitory postsynaptic potentials.     

Regional features of background electrical activity and of direct cortical response by the intact or neuronally isolated cortex

Background electrical activity and thresholds for the appearance of direct cortical responses (DCR) were studied in acute and chronic experiments on cats in some gyri of the intact and neuronally isolated cortex (the whole cortex was subjected to neuronal isolation [10]). It was determined that in intact animals the suprasylvian gyrus, particularly its central part, differs by its higher electrical activity and lower DCR thresholds from the ectosylvian gyrus. These differences are retained after neuronal isolation of the cortex from the subcortical structures. Hence the differences found in the neurophysiologic characteristics of the gyri under study reflect specific properties and are not mediated by subcortical neural effects.Institute of Experimental Medicine, Academy of Medical Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 2, No. 1, pp. 52–58, January–February, 1970.     

Effect of damage to the zone of the medial forebrain bundle and preoptic area on the activiy of a penicillin-induced epileptiform focus (phenomenon of the hyperactive determinant dispatch station)]

It was shown in experiments on cats under nembutal anesthesia that a lesion of the medial forebrain bundle (MFB) and partly of the preoptic region at the side of local penicillin application on the cerebral cortex (g. suprasylvius medius) results in depression of the epileptiform activity in the penicillin-induced focus, as well as in the secondary "mirror" focus, which appeared in the symmetrical cortex area of the other hemisphere. The MFB lesion at the "mirror" focus side led to depression of the seizure spike potentials in this focus only and did not change the activity in the primary epileptiform one. The described effects are considered from the aspect of the conception on the role of the determinant dispatch station (DDS) in the central nervous system: the primary epileptiform focus plays the role of the hyperactive DDS which induces the secondary focus and determines the character of its activity. The results of the study substantiate a suggestion that the MFB can take part in the modulation of the cortical epileptiform activity.     

Electrocorticographic development of epileptogenic foci in the occipital region of the rat cerebral cortex

The development of cortical penicillin foci in the occipital region was studied in rats whose ages ranged from five days up to the adult age. The local application of penicillin induced the formation of an epileptogenic focus for the first time at the age of seven days. With advancing age, the amplitude of focal discharges increased, the duration of the individual components of the discharge shortened, its originally negative-positive configuration changed to a triphasic form and in the third week of life initial positivity, for a time, become the dominant component of the discharge. Projection of the discharges to the contralateral hemisphere was found to be inconstant in the second postnatal week, but appeared regularly from the age of 14 days. Synchronization of the discharges of two symmetrical foci was very poor in 7-day-old young, but improved noticeably by the 14th day; it was never complete, however, even in adulthood. The activity of symmetrical foci changed spontaneously to ECoG seizures, which were most common in 7-day-old young (in which ictal activity was usually not generalized, however) and were least frequent in 14-day-old animals. Focal discharges could not be reliably triggered by electrical stimulation of the contralateral cortex until the age of 18 days and later. The occipital part of the cortex develops somewhat later than the sensorimotor, frontal region, and during its development there also appeared phenomena which are not present in the frontal cortex.     

Histone alteration in the nuclei of different types of neurons in a "mirror" epileptiform focus in rat brain]

Total histones estimated after M. Alfred and I. Geschwind were studied cytophotometrically in nuclei of neurons of different types (layers III and V in the frontal-parietal cortex and in the thalamic lateral nucleus) of the "mirror" epileptiform focus in the rat brain on the 11th and 63d day after cobalt implantation. On the 11th day of the experiment, integral optic density of the histones decreased by 33%, 25% and 37%, and the area of the nuclei -- by 27%, 24% and 35% in the neurons of layers II and V in the frontal-parietal cortex and in the thalamic lateral neucleus, respectively. On the 63d, integral optic density of the histones in the neurons mentioned increased respectively by 42%, 52% and 42%, and the area of the nuclei -- by 21%, 43% and 27%. Concentration of the histones in the nuclei decreased by 3--9% on the 11th day and increased, except layer V, by 9--18% on the 63d of the experiment. Interconnection between changes in histone content and total proteins in cytoplasm of functionally different neurons in the "mirror" epileptiform focus is disscussed, with special reference to histones as a regular of genetic activity for protein synthesis.     

Changes in Choline Acetyltransferase Activity and High-Affinity Choline Uptake,but Not in Acetylcholinesterase Activity and Muscarinic Cholinergic Receptors,in Rat Somatosensory Cortex after Sciatic Nerve Injury

Selected cholinergic markers (choline acetyltransferase, acetylcholinesterase, muscarinic acetylcholine receptor, high-affinity choline uptake) were studied in the hindlimb representation areas of the rat somatosensory cortex and within the visual cortex 1 to 63 days after unilateral transection of the sciatic nerve. In the contralateral somatosensory cortex, peripheral deafferentation resulted in a significant reduction of choline acetyltransferase activity (by 15%) 3 days after sciatic nerve injury, and in a significant reduction of high-affinity choline uptake (by 30%) 1 day after nerve transection, in comparison to untreated control rats. Investigations in individual cortical layers revealed that the decrease of both choline acetyltransferase activity and high-affinity choline uptake sites was mainly due to reductions in cortical layer V. Acetylcholinesterase activity and [³H]quinuclidinyl benzilate binding to muscarinic acetylcholine receptors were not affected by unilateral transection of the sciatic nerve. In the ipsilateral somatosensory cortex, as well as in the visual cortex at both cortical hemispheres, no significant changes in the cholinergic parameters studied could be detected. The data indicate that peripheral deafferentation of the somatosensory cortex results in a transient change of presynaptic cholinergic parameters within the affected somatosensory area as early as 1 to 3 days after the lesion; thus, they emphasize the involvement of cholinergic mechanisms in cortical reorganizational events.     

Changes in choline acetyltransferase activity and high-affinity choline uptake, but not in acetylcholinesterase activity and muscarinic cholinergic receptors, in rat somatosensory cortex after sciatic nerve injury

Selected cholinergic markers (choline acetyltransferase, acetylcholinesterase, muscarinic acetylcholine receptor, high-affinity choline uptake) were studied in the hindlimb representation areas of the rat somatosensory cortex and within the visual cortex 1 to 63 days after unilateral transection of the sciatic nerve. In the contralateral somatosensory cortex, peripheral deafferentation resulted in a significant reduction of choline acetyltransferase activity (by 15%) 3 days after sciatic nerve injury, and in a significant reduction of high-affinity choline uptake (by 30%) 1 day after nerve transection, in comparison to untreated control rats. Investigations in individual cortical layers revealed that the decrease of both choline acetyltransferase activity and high-affinity choline uptake sites was mainly due to reductions in cortical layer V. Acetylcholinesterase activity and [3H]quinuclidinyl benzilate binding to muscarinic acetylcholine receptors were not affected by unilateral transection of the sciatic nerve. In the ipsilateral somatosensory cortex, as well as in the visual cortex at both cortical hemispheres, no significant changes in the cholinergic parameters studied could be detected. The data indicate that peripheral deafferentation of the somatosensory cortex results in a transient change of presynaptic cholinergic parameters within the affected somatosensory area as early as 1 to 3 days after the lesion; thus, they emphasize the involvement of cholinergic mechanisms in cortical reorganizational events.     

Electroencephalographic study of iron-induced chronic focal cortical epilepsy in rat: propagation of cortical epileptic activity to substantia nigra and thalamus.

Cortical epileptic focus was produced by an intracortical injection of FeCl3 in rat cerebral cortex using standard techniques. How after its onset in the cortical focus, the epileptiform activity evolved with time in the thalamus and substantia nigra has been determined. To study the propagation of the epileptiform activity, the local EEG and multiple unit action potentials were recorded from these structures simultaneously with the cortical epileptiform EEG. The results showed that in thalamus and substantia nigra epileptiform activity appeared simultaneously with that in the cortical focus. Intensity of epileptic activity in thalamus and substantia nigra on the whole increased in parallel with that in the cortical focus. The results suggest that the thalamic and nigral epileptiform activity may reinforce the cortical epileptiform activity.     

Evoked potentials in the parietal cortex in response to stimulation of the posterolateral nucleus of the thalamus in kittens of different ages

In kittens of the first month of postnatal life, studies have been made of the evoked potentials in the parietal cortex elicited by stimulation of the posterior lateral thalamic nuclei. It is suggested that within the first days of life the EPs result mainly from the electrical activity of the deep (V-VI) layers of the cortex. This suggestion is confirmed by a significant increase in the velocity of the rising phase and the decrease of the duration of the EPs in the deep layers in newborn animals, as well as partial inversion of the negative wave of the EP at the level of these layers in 1-week kittens. Total depth of the median layers in 1-week kittens is twice less than that in 1 month old ones. To the end of the 2nd week, the input of the activity of the median layers into total activity increases: the focus of partial inversion of the negative wave of the EPs is translocated upward to the border of layers II-III. In 1-month kittens, the general pattern of the EPs in the parietal cortex is the same as in adult cats.     

Cortico-cortical connections in the parietal area of the cerebral cortex

Layer-by-layer arrangement of the commissural and associative fibers has been studied in the cat parietal cortex. The commissural fibers are distributed in all the layers of the parietal cortex in the contralateral hemisphere, except the superficial part of the I layer. These fibers mainly terminate in the III, IV layers of the contralateral parietal cortex, though their termination in other layers is not excluded. The associative fibers of the parietal cortex are distributed in all the layers of the sensomotor area, except the superficial part of the I layer. They mainly terminate in the III, IV, V layers of the primary somatosensory and in the III, V layers of the motor cortex.     

Perception matches selectivity in the human anterior color center

Human ventral cortex contains at least two visual areas selective for color [1]: a posterior center in the lingual gyrus labeled V4 [2-4], V8 [5], or VO-1 [6] and an anterior center in the medial fusiform that has been labeled V4alpha[3, 4]. We examined the properties of the anterior color center using electrical recording and electrical stimulation in a subject with an electrode implanted over the anterior color center, as determined with BOLD fMRI in the same subject. Presentation of visual stimuli evoked local field potentials from the electrode. Consistent with fMRI, the potentials were larger for chromatic than achromatic stimuli. The potentials differed depending on stimulus color, with blue-purple colors evoking the largest response. The spatial receptive field of the electrode was central/parafoveal with a contralateral bias. In the absence of a visual stimulus, electrical stimulation of the electrode produced an artificial visual percept of a blue-purple color near the center of gaze. These results provide direct evidence of a tight link between selectivity and perception in ventral temporal cortex. Electrical stimulation of the anterior color center is sufficient to produce the conscious percept of a color whose identity is determined by the selectivity of the stimulated neurons.     

Binocular interaction in the parastriatal rat cortex during a change in intensity of one monocular stimulus

Binocular interaction in symmetrical centers of the parastriatal cortex in rats was investigated by the evoked potentials method before and after callosotomy. A model was used in which one eye was always stimulated by flashes of average intensity and the other by flashes of average intensity. The presence of contralateral and ipsilateral facilitation, increasing with the strength of the stimulus, was demonstrated; contralateral facilitation was more effective than ipsilateral. Synergism in the development of the contralateral and ipsilateral effects is emphasized, distinguishing them from the corresponding processes in the striatal cortex. After callosotomy the contralateral and ipsilateral facilitatory effects are intensified.Biological Institute, Leningrad University. Translated from Neirofiziologiya, Vol. 5, No. 2, pp. 128–132, March–April, 1973.     

The vestibular cortical projection during spinal decompensation

The removal of spinal afferents in rabbits submitted to unilateral lesion of the labyrinth and fully compensated greatly modified the field potentials as well as the single unit responses recorded from the cortical vestibular area during stimulation of the intact eighth nerve. In particular, an increase of contralateral and a decrease of ipsilateral potentials were observed. These asymmetrical responses indicate that the influence of the spinal cord in compensating the effects of unilateral lesion of the labyrinth is directed to balance not only the electrical activity of the brain-stem structures, but also that of the cerebral cortex. It appears, therefore, that spinal signals intervene not only in the compensation of vestibulospinal and vestibulo-oculomotor functions but also of cortical functions, such as that related to vestibular sensation.     

A neural network model of attention-modulated neurodynamics

Visual attention appears to modulate cortical neurodynamics and synchronization through various cholinergic mechanisms. In order to study these mechanisms, we have developed a neural network model of visual cortex area V4, based on psychophysical, anatomical and physiological data. With this model, we want to link selective visual information processing to neural circuits within V4, bottom-up sensory input pathways, top-down attention input pathways, and to cholinergic modulation from the prefrontal lobe. We investigate cellular and network mechanisms underlying some recent analytical results from visual attention experimental data. Our model can reproduce the experimental findings that attention to a stimulus causes increased gamma-frequency synchronization in the superficial layers. Computer simulations and STA power analysis also demonstrate different effects of the different cholinergic attention modulation action mechanisms.     

A Simple Rule for Dendritic Spine and Axonal Bouton Formation Can Account for Cortical Reorganization after Focal Retinal Lesions

Lasting alterations in sensory input trigger massive structural and functional adaptations in cortical networks. The principles governing these experience-dependent changes are, however, poorly understood. Here, we examine whether a simple rule based on the neurons'' need for homeostasis in electrical activity may serve as driving force for cortical reorganization. According to this rule, a neuron creates new spines and boutons when its level of electrical activity is below a homeostatic set-point and decreases the number of spines and boutons when its activity exceeds this set-point. In addition, neurons need a minimum level of activity to form spines and boutons. Spine and bouton formation depends solely on the neuron''s own activity level, and synapses are formed by merging spines and boutons independently of activity. Using a novel computational model, we show that this simple growth rule produces neuron and network changes as observed in the visual cortex after focal retinal lesions. In the model, as in the cortex, the turnover of dendritic spines was increased strongest in the center of the lesion projection zone, while axonal boutons displayed a marked overshoot followed by pruning. Moreover, the decrease in external input was compensated for by the formation of new horizontal connections, which caused a retinotopic remapping. Homeostatic regulation may provide a unifying framework for understanding cortical reorganization, including network repair in degenerative diseases or following focal stroke.     

Manifestation of integrative activity in the neuronally isolated cortex]

By the slow bioelectrical activity parameter, with vector representation of experimental data, an attempt was made to reveal elements of integrative activity in the neuronally isolated cortex at early stages after its isolation from subcortical formations. Animals with an intact cerebral cortex were used as controls. It has been found that in spite of isolation of the cerebral cortex from synaptic influences of the subcortical structures, it possesses even at early stages after isolation (10--17th day) its own mechanisms of integrative activity, providing for the organization of background and evoked activity which are gradually normalized by the 30th to 40th day, without however reaching the level of activity of the intact cerebral cortex.     

The role of the corpus callosum in the interhemispheric transmission of epileptic electrical activity.

In acute experiments on 49 curarized adult rats without general anaesthesia, we studied the transmission of discharges of cortical penicillin foci between the two hemispheres after transecting the corpus callosum. Projected discharges of the cortical penicillin focus appeared in the contralateral hemisphere later than in the controls and had a very different shape. The interhemispheric response of the experimental rats consisted of a small positive and a small negative deflection with long latent periods. Focal discharges could be triggered by electrical stimulat;on of the contralateral hemisphere only irregularly and for short periods of time. In rats with a transected corpus callosum, two symmetrical cortical foci at first behaved independently of each other; their synchronization then slowly improved, but never attained 100 per cent. The corpus callosum is the preferential pathway for interhemispheric transmission of focal activity. Transection of this pathway makes the transmission conditions much worse, but further connections, with a longer conduction time and lower efficacy, gradually come into action.