Isocortical Hyperemia and Allocortical Inflammation and Atrophy Following Generalized Convulsive Seizures of Thalamic Origin in the Rat

1. Generalized convulsive seizures can be elicited by a single unilateral microinjection of the cholinergic muscarinic agonist, carbachol, into the specific sites of the thalamus including ventral posterolateral and the reticular thalamic nuclei. The implication of the thalamic specific and reticular neurons is reviewed and discussed.2. On the basis of the c-fos regional expression and well-known efferent and afferent pathways linking these regions, a neuronal network relating the limbic, thalamo–striatal–cortical, and central autonomic systems, was constructed.3. The pattern of Fos immunoreactivity associated with long-lasting isocortical vasodilatation elicited by generalized convulsive seizures in anesthetized rat following cholinergic stimulation of the thalamus can be attributed to both the electrocortical activity and the long-lasting increase in cortical blood flow. We propose that the sustained cerebral cortical blood flow response during convulsive epileptic seizures may implicate intracerebral vasodilatory and vasoconstrictory neural mechanisms. Double-labeled NADPH-d and Fos-positive neurons implicated in maintaining the sustained isocortical vasodilatory response were found in the anterior lateral hypothalamic area. Inhibition of these neurons prevented the increase in cortical blood flow despite an increased metabolic demand manifested by the ictal electrocortical activity.4. Medial temporal lobe atrophy, including hippocampus, amygdala, and parahippocampal gyrus (piriform and entorhinal cortices) are the most common pathology in man. However the origin of medial lobe atrophy remain uncertain. Our results provide evidence that the allocortical microvascular inflammation may be in origin of the neurovascular degenerative processes leading to atrophy.     

Central neural mechanisms that interrelate sensory and affective dimensions of pain

The perception of pain is highly complex, and requires neural integration from a variety of routes. Spinal pathways to the amygdala, hypothalamus, reticular formation, medial thalamic nuclei, and limbic cortical structures transmit information involved arousal, bodily regulation, and emotional responses. Other, albeit indirect, pathways can carry signals to these same structures, for example, from spinal pathways to somatosensory thalamic and cortical areas, and from these to cortical limbic structures. Indirect cortico-limbic pathways integrate nociception with information about the status of the body and indirect routes must culminate in the prioritization of emotions and responses to pain.     

Unit responses of the first and second somatosensory cortical areas to peripheral,thalamic, and cortical stimulation

Unit responses of the first (SI) somatosensory area of the cortex to stimulation of the second somatosensory area (SII), the ventral posterior thalamic nucleus, and the contralateral forelimb, and also unit responses in SII evoked by stimulation of SI, the ventral posterior thalamic nucleus, and the contralateral forelimb were investigated in experiments on cats immobilized with D-tubocurarine or Myo-Relaxin (succinylcholine). The results showed a substantially higher percentage of neurons in SII than in SI which responded to an afferent stimulus by excitation brought about through two or more synaptic relays in the cortex. In response to cortical stimulation antidromic and orthodromic responses appeared in SI and SII neurons, confirming the presence of two-way cortico-cortical connections. In both SI and SII intracellular recording revealed in most cases PSPs of similar character and intensity, evoked by stimulation of the cortex and nucleus in the same neuron. Latent periods of orthodromic spike responses to stimulation of nucleus and cortex in 50.5% of SI neurons and 37.1% of SII neurons differed by less than 1.0 msec. In 19.6% of SI and 41.4% of SII neurons the latent period of response to cortical stimulation was 1.6–4.7 msec shorter than the latent period of the response evoked in the same neuron by stimulation of the nucleus. It is concluded from these results that impulses from SI play an important role in the afferent activation of SII neurons.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 8, No. 4, pp. 351–357, July–August, 1976.     

Comparative study of effects of cortical nucleus of amygdala and pyriform cortex on activity of bulbar respiratory neurons in cats

Comparative microelectrophysiological study of character and peculiarities of effects of the cortical nucleus of amygdala and of the periamygdalar area of pyriform cortex on impulse activity was performed on the same single functionally identified respiratory medullar neurons. A high reactivity of bulbar respiratory neurons on stimulation is established in both studied limbic structures. There is established the qualitatively different character of their response reactions at stimulation of the cortical amygdala nucleus and the periamygdalar cortex. The cortical amygdala nucleus has been shown to produce on the activity of medullar respiratory neurons both facilitating and inhibitory action with predominance of the activating one (without topographical orderliness). The effect of periamygdalar cortex at stimulation of various parts was characterized by topographic differentiation. The suppressing reactions of neurons in the majority of cases were recorded at stimulation of the rostral area of periamygdalar cortex, whereas the excitatory reactions--at stimulation of its caudal part. Functional organization of respiratory control of the studied limbic system structures is discussed.     

Comparative study of effect of cortical nucleus of amygdala and pyriform cortex on activity of bulbar respiratory neurons in cats

Comparative microelectrophysiological study of character and peculiarities of effects of the cortical nucleus of amygdala and of the periamygdalar area of pyriform cortex on impulse activity was performed on the same single functionally identified respiratory medullar neurons. A high reactivity of bulbar respiratory neurons to stimulation is established in both studied limbic structures. There is established the qualitatively different character of their response reactions at stimulation of the cortical amygdala nucleus and the periamygdalar cortex. The cortical amygdala nucleus has been shown to produce both facilitating and inhibitory effects (with predominance of the activating one) on activity of medullar respiratory neurons (without topographical orderliness). The effect of periamygdalar cortex at stimulation of various parts was characterized by topographic differentiation. The suppressing reactions of neurons in the majority of cases were recorded at stimulation of the rostral area of periamygdalar cortex, whereas the excitatory reactions-at stimulation of its caudal part. Functional organization of respiratory control of the studied limbic system structures is discussed.     

Analysis of long cortical evoked potentials

Evoked potentials arising in the motor cortex in response to its direct stimulation (dendritic and slow negative potentials), to stimulation of the ventrolateral (primary response) and intralaminar (nonspecific response) thalamic nuclei, and to stimulation of the pyramidal tracts (antidromic response), and also postsynaptic responses of neurons corresponding to them were studied in acute experiments on curarized cats. Evoked potentials arising in response to direct cortical stimulation and also to stimulation of the specific and nonspecific thalamic nuclei and pyramidal tracts were recorded from the same point of the motor cortex, and the corresponding intracellular responses were recorded from the same neuron. Slow negative potentials arising under these conditions of stimulation and the IPSPs corresponding to them were shown to have an identical time course. The results show that slow negative potentials are a reflection of hyperpolarization of pyramidal neurons. It is suggested that the individual components of responses evoked by direct stimulation of the cortex and thalamic nuclei have a common genesis.I. S. Beritashvili Institute of Physiology, Academy of Sciences of the Georgian SSR, Tbilisi. Translated from Neirofiziologiya, Vol. 14, No. 2, pp. 115–121, March–April, 1982.     

Effect of stimulation of the amygdala and subthalamus on unit activity of the mesencephalic central gray matter

Characteristics of unit activity of the mesencephalic central gray matter were studied during electrical stimulation of the amygdala and subthalamus (chiefly the zona incerta) in acute experiments on rats. Stimulation of the amygdala evoked chiefly inhibitory unit responses (72%), whereas stimulation of the zona incerta evoked chiefly excitatory responses (59%). The effectiveness of regular (5 Hz) stimulation of the amygdala in producing prolonged changes in unit activity was noted and points to the modulating character of the influence of this structure on the central gray matter. In 31 of 114 neurons tested convergence of impulses from the amgydala and zona incerta was observed. The two types of stimulation most frequently induced inhibition (71%).Institute of Physiology, Siberian Branch, Academy of Medical Sciences of the USSR, Novosibirsk. Translated from Neirofiziologiya, Vol. 10, No. 3, pp. 245–251, May–June, 1978.     

Depression of evoked potentials in rat thalamic ventro-basal complex and somatosensory cortex after reticular stimulation

Experiments on unanesthetized rats immobilized with D-tubocurarine showed that electrical stimulation (100/sec) of the central gray matter and the mesencephalic and medullary reticular formation considerably depressed potentials in the somatic thalamic relay nucleus and somatosensory cortex evoked by stimulation of the forelimb or medial lemniscus. The mean threshold values of the current used for electrical stimulation of these structures did not differ significantly and were 70 (20–100), 100 (20–120), and 120 (50–200) µA, respectively. On comparison of the amplitude-temporal characteristics of inhibition of evoked potentials during electrical stimulation of the above-mentioned structures by a current of twice the threshold strength, no significant differences were found. Immediately after the end of electrical stimulation the amplitude of the cortical evolved potential and the post-synaptic components of the thalamic evoked potential was 50–60% (P<0.01) below the control values. The duration of this depression varied from 0.5 to 1 sec. An increase in the intensity of electrical stimulation of brain-stem structures to between three and five times the threshold led to depression of the presynaptic component of the thalamic evoked potential also. Depression of the evoked potential as described above was found with various ratios between the intensities of conditioning and testing stimuli.M. V. Lomonosov Moscow State University. Translated from Neirofiziologiya, Vol. 8, No. 5, pp. 467–475, September–October, 1976.     

A thalamo-cortical neural mass model for the simulation of brain rhythms during sleep

Cortico-thalamic interactions are known to play a pivotal role in many brain phenomena, including sleep, attention, memory consolidation and rhythm generation. Hence, simple mathematical models that can simulate the dialogue between the cortex and the thalamus, at a mesoscopic level, have a great cognitive value. In the present work we describe a neural mass model of a cortico-thalamic module, based on neurophysiological mechanisms. The model includes two thalamic populations (a thalamo-cortical relay cell population, TCR, and its related thalamic reticular nucleus, TRN), and a cortical column consisting of four connected populations (pyramidal neurons, excitatory interneurons, inhibitory interneurons with slow and fast kinetics). Moreover, thalamic neurons exhibit two firing modes: bursting and tonic. Finally, cortical synapses among pyramidal neurons incorporate a disfacilitation mechanism following prolonged activity. Simulations show that the model is able to mimic the different patterns of rhythmic activity in cortical and thalamic neurons (beta and alpha waves, spindles, delta waves, K-complexes, slow sleep waves) and their progressive changes from wakefulness to deep sleep, by just acting on modulatory inputs. Moreover, simulations performed by providing short sensory inputs to the TCR show that brain rhythms during sleep preserve the cortex from external perturbations, still allowing a high cortical activity necessary to drive synaptic plasticity and memory consolidation. In perspective, the present model may be used within larger cortico-thalamic networks, to gain a deeper understanding of mechanisms beneath synaptic changes during sleep, to investigate the specific role of brain rhythms, and to explore cortical synchronization achieved via thalamic influences.     

Influence of certain stimulation parameters on the character of the cortical self-sustained after-discharge

The ECoG pattern of self-sustained after-discharges (SSADs) evoked by rhythmic electrical stimulation of the cerebral cortex is far from uniform. In acute experiments on male rats the authors studied the significance of the frequency, intensity and length of stimulation for the character of the resultant SSAD. In the first group (11 rats), a stimulation frequency of 8 Hz was used; the stimulation series, which lasted 10 and 20 s, always led to the formation of a SSAD composed of spike-and-wave rhythm right from the outset. Shortening the time of stimulation markedly reduced its effectiveness. In the second group (10 animals), stimulation with 50 Hz frequency often evoked a complex SSAD starting with desynchronization, which was followed by fast spike activity of increasing amplitude and only later by spike-and-wave rhythm or by polyspike-and-wave rhythm. Towards the end, serrated waves--i.e. graphoelements typical of SSADs evoked by electrical stimulation of limbic structures--often appeared in the SSAD. A higher stimulation intensity increased the incidence of this complex SSAD. In this group a minimum duration of stimulation was also essential (series of less than 2 s were not reliably effective). When this second type of SSAD ended, depression of ECoG activity was followed in 27% of the cases by a spontaneous recurrent seizure (RS). The ECoG character of these RS can be very variable. The two types of seizures evoked by slow and fast stimulation differ from each other not only in respect of their ECoG pattern (where the difference is probably due to more pronounced propagation to subcortical structures after faster stimulation), but also as regards the presumed mechanism of their onset.     

Investigation of the functional role of the septum

A spectral-correlation analysis was made of the EEG recorded from the motor and visual cortex, hippocampus, and septum (in some series of experiments, the lateral geniculate body and mesencephalic reticular formation also) of rabbits in the presence or absence (background) of sensory stimulation. To investigate the functional role of the septum as a pacemaker the method of "rhythm binding" by electrical stimulation of the septum (lateral and medial nuclei) was used. By electrical stimulation of the medial nucleus of the septum at a frequency of 4–30 Hz rhythm binding was successfully obtained in all regions studied. Maximal rhythm binding was observed in cortical potentials. It is postulated that cortical rhythmic activity is generated as a result of physiological interaction between cortex and septum.Institute of Higher Nervous Activity and Neurophysiology, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 8, No. 3, pp. 267–275, May–June, 1976.     

Responses of limbic cortical neurons to stimulation of splanchnic and sciatic nerves and of the mammillary bodies

Spontaneous and evoked unit activity in the anterior limbic cortex in response to stimulation of the splanchnic and sciatic nerves and of the mammillary region of the hypothalamus were recorded extracellularly in acute experiments on cats. The study of heterogeneous transsynaptic influence on limbic cortical neurons showed that in the presence of effective sensory viscerosomatic convergence, weak convergence of influences from the central hypothalamic and peripheral sources took place. Short-latency responses of limbic cortical neurons to stimulation of the mammillary bodies consisted of orthodromic and antidromic responses, evidence of the existence of short two-way connections between the anterior limbic cortex and mammillary nuclei of the hypothalamus.L. A. Orbeli Institute of Physiology, Academy of Sciences of the Armenian SSR, Erevan. Translated from Neirofiziologiya, Vol. 11, No. 5, pp. 419–426, September–October, 1979.     

Analysis of the effects of electrical stimulation of certain limbic structures

It has been established that stimulation of the structures of the limbic system (hippocampus, amygdaloid complex, septum) and the medial nucleic of the thalamus of rabbits in conditions of free behavior elicits four basic types of behavioral reactions: arousal, orientation-investigatory, aggressive-defensive and various epileptiform (convulsive) reactions. Activation of behavior, i.e., arousal and the orientation-investigatory reaction, constantly appear on stimulation of the unspecific thalamic nuclei. The aggressive-defense reaction is elicited by stimulating the nuclei of the amygdaloid complex of the ventral part of the hippocampus and the ventromedial nuclei of the thalamus. The epileptiform reactions are most readily reproduced on stimulation of the amygdaloid complex and the ventral part of the hippocampus. The threshold for the appearance of discharges of the aftereffect is very low. The latter are more sustained on stimulation of the basolateral part of the amygdala and the ventral part of the hippocampus. In rabbits as compared with higher animals the discharges on stimulation rapidly spread not only to the limbic system but also to the reticular formation and the neocortex.Kharkov Medical Institute. Translated from Neirofiziologiya, Vol. 1, No. 2, pp. 194–201, September–October, 1969.     

Stimulation of the hippocampus and its effect on electrographic manifestations of the brain in unrestrained rats.

The dorsal hippocampus was electrically stimulated in unanaesthetized, unrestrained rats with a cobalt-gelatin rod in their cortex. The significance of the hippocampus in the elicitation of both physiological spontaneous rhythmic activity (episodic activity of 8--9/sec frequency bound, in rats, to a state of quiet wakefulness, and "sleep spindles") and pathological rhythmic activity of the self-sustained after-discharge (SSAD) type was determined from the aspect of the EEG and behavioural characteristics. 1. Single electrical pulses (0.1 msec, 1--10 V, 0.3/sec) elicited an evoked potential bilaterally in the somatosensory cortex. Elicitation of rhythmic after-activity (of the type of episodes or sleep spindles) was observed only in some cases in which an adequately strong stimulus was used. 2. Repeated series of rhythmic electrical stimuli following each other at short intervals (2--3 min) led to the formation of SSAD in about one third of the cases and at all stimulation frequencies (3-15/sec), although low frequencies (3--4/sec) were the least effective. The character of the SSAD and simultaneous behavioural phenomena differed fundamentally from those evoked by electrical stimulation of the thalamus (Chocholová et al. 1977). The development of paroxysmal after-activity was signalled by responses of a more or less distinct "recruiting" character during stimulation. On the basis of a comparison of electrographic and behavioural manifestations after electrical stimulation of the thalamus and hippocampus, the possibility of both thalamic and extrathalamic projection from the hippocampus to the cortical region is considered.     

Role of cholinergic mechanisms in the genesis of some cortical responses

The dynamics of evoked potentials during blocking of cholinergic cortical structures was investigated in unanesthetized cats. Application of the anticholinergic drug benactyzine inhibits the negative phases of cortical responses to stimulation of the reticular formation and non-specific thalamic nuclei and also of responses to direct cortical stimulation. Direct cortical responses (DCRs), inverted by -aminobutyric acid, are also depressed, indicating the role of cholinergic mechanisms in the genesis of these responses. During blocking of cholinergic synapses, negative phases of the primary response (PR) and response to stimulation of the specific thalamic nucleus are facilitated. A tendency is then observed toward grouping of spontaneous unit discharges and abolition of inhibition of cortical neurons produced by high-frequency stimulation of the reticular formation. One cause of the increase in amplitude of the primary response (PR) to the action of anticholinergic drugs may be widening of the zone of cortical neurons involved in the response because of abolition of the localizing effect of inhibitory neurons.Institute of Physiology, Siberian Division, Academy of Sciences of the USSR, Novosibirsk. Translated from Neirofiziologiya, Vol. 2, No. 4, pp. 406–411, July–August, 1970.     

Analysis of evoked potentials from the limbic cortex

In acute experiments on cats we investigated evoked potentials from the cingulate gyrus developed in response to stimulation of somatic and visceral nerves; also potentials from various parts of the hypothalamus, and midbrain reticular formation. We showed that the nonspecific afferent system influences electrical activity in the limbic cortex through hypothalamic pathways. We consider the limbic cortex to be part of the association area of the neocortex and that the associative responses of the cortex are more complex in nature than is usually thought to be the case, and that they are formed under the influence of impulses arriving at the cortex along many specific and nonspecific pathways. The hypothalamo—cingulate system is one of the main systems of cortico—subcortical integration. It plays an important part in regulation of autonomic, somatic, and emotional responses.L. A. Orbeli Institute of Physiology, Academy of Sciences of the Armenian SSR, Erevan. Translated from Neirofiziologiya, Vol. 2, No. 5, pp. 451–459, September–October, 1970.     

Responses of limbic cortical neurons during instrumental conditioned reflexes in cats

Unit activity in cortical areas 24 and 32 was studied during conditioned placing reflex formation in cats. Neuronal responses in the limbic cortex of trained animals correlated with acoustic stimulation, the motor response, and also with the presentation of food reinforcement. In untrained animals 16% of neurons responded to acoustic stimulation. After training the number of neurons responding to sound in area 32 increased to 51.3%. Of the total number of neurons, 34.6% responded by initial excitation and 26.7% by inhibition of spike activity. The latent period of these responses was about 50 msec and their duration up to 200 msec. Similar but weaker responses were observed in area 24. Short-latency activation responses to conditioned and differential stimulation were similar in character. It is suggested that after training processes taking place in the limbic cortex may contribute to better perception of both conditioned and differential acoustic stimuli, irrespective of their functional significance.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 16, No. 2, pp. 201–208, March–April, 1984.     

Effect of electric stimulation of cortical portions of the limbic system on the activity of neurons of the anterior thalamic nuclei in the rabbit

Effects of electrical stimulation of the subiculum (SB) and posterior limbic cortex (PLC) were studied extracellularly in the anteroventral (AV) and anterodorsal (AD) limbic thalamic nuclei of awake chronic rabbits. Stimulation of SB and PLC evoked in some AV neurones discharges of 1-2 spikes. Gradual potentiation and low frequency of following (up to 10-15 Hz) were characteristic of these responses. Activity of the majority of AV cells was suppressed by stimulation with appearance of inactivation bursts, "neuronal spindles" and modulation on delta-frequencies. Spike responses were evoked by SB and (rarely) by PLC stimulation only in a certain class of AD neurones which tentatively are regarded as relay cells. The neurones with high-frequency, low-amplitude discharges (putative inhibitory interneurones) reacted to stimulation of PLC and to a lesser extent of SB by prolonged series of spikes (150 ms--2s). Stimulation of PLC exerted prolonged influence upon neuronal responses to sensory stimuli.     

Unit responses of the cat caudate nucleus to cortical stimulation before and after destruction of nonspecific thalamic nuclei

Responses of caudate neurons to stimulation of the anterior sigmoid and various parts of the suprasylvian gyrus were studied in acute experiments on cats. The experiments consisted of two series: on animals with an intact thalamus and on animals after preliminary destruction of the nonspecific thalamic nuclei. Stimulation of all cortical areas tested in intact animals evoked complex multicomponent responses in caudate neurons with (or without) initial excitation, followed by a phase of inhibition and late activation. The latent periods of the initial responses to stimulation of all parts of the cortex were long and averaged 14.5–25.5 msec. Quantitative and qualitative differences were established in responses of the caudate neurons to stimulation of different parts of the cortex. Considerable convergence of cortical influences on neurons of the caudate nucleus was found. After destruction of the nonspecific thalamic nuclei all components of the complex response of the caudate neurons to cortical stimulation were preserved, and only the time course of late activation was modified.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 12, No. 5, pp. 464–471, September–October, 1980.     

Investigation of electrical responses recorded from the fenestra cochleae in cats

Electrical responses of the fenestra cochleae to stimulation by clicks of different intensity, polarity, and frequency, were studied in anesthetized cats. The absolute values of amplitude and latent period of the neural component of the response reflect the physiological state of the auditory nerve. Besides ordinary potentials characterized by peaks N1 and N2, specific responses were observed when clicks with an intensity of 85 dB or "rarefaction" clicks were used. Dependence of the amplitude of these responses on the intensity of acoustic stimuli of different polarity was investigated during a change in the rhythm of the stimulation; the effect of different rhythms of stimulation on the gradient of the curve reflecting this relationship was examined. The possible mechanisms of the effect of stimulus frequency are discussed.Scientific-Research Institute of Otolaryngology, Ministry of Health of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 11, No. 2, pp. 151–157, March–April, 1979.