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O S Vinogradova

Publications and source records attributed to O S Vinogradova.

At least 19 recordsLinked to original sources

The paradoxically high reactivity of septal neurons in hibernating ground squirrels to endogenous neuropeptides is lost after chronic deafferentation of the septum from the preopticohypothalamic areas.

The effect of neuropeptides (TSKYR, TSKY and DY) and neurotransmitters (serotonin and noradrenaline) on the activity of medial septum (MS) neurons from the brain of summer wakening ground squirrels (WGS), hibernating ground squirrels (HGS), and hibernating ground squirrels with the undercut septum (UHGS) was studied. It was shown that in HGS, the neuropeptides were substantially more effective in modulating the spontaneous activity of MS neurons than in WGS. The undercutting of MS led to the disappearance of the increased responsiveness to the neuropeptides: in UHGS, neuropeptide-induced changes in the spontaneous activity became nearly identical to those in WGS. The decrease in MS responsiveness in UHGS is due mainly to pacemaker neurons, which cease to respond to the peptides. It was shown that the neuropeptides have a dual effect: they change the level of spontaneous activity through direct modulation of pacemaker potential and control responses to electrical stimulation by modulating the synaptic transmission. Contrary to neuropeptides, neurotransmitters were highly effective in neurons of all groups of animals. Presumably, the enhanced excitability of MS during hibernation, which is necessary for performing the 'sentry post' function, is formed under the influence of the preopticohypothalamic area, and this influence is mediated by peptides.

Action Potentials↗

Neuropeptide modulation of evoked responses of neurons in the medial septal region of hibernating ground squirrels in conditions of chronic isolation of the medial septal region from preoptic-hypothalamic structures.

Septal slices from hibernating ground squirrels were initially (for two weeks) subjected to basal separation of the septal region and were then used for studies of the effects of neuropeptides extracted from the brains of hibernating animals (TSKYR, TSKY, and DY) and monoaminergic neurotransmitters (noradrenaline and serotonin) on neuronal responses evoked by intraseptal electrical stimulation. Despite removal of a large complex of afferent connections and direct contacts with the preoptic region, the neurons retained their normal reactivity and the normal distribution of response types. Neuropeptides efficiently modulated responses, and had strong facilitatory effects on oligosynaptic short-latency responses consisting of single spikes. In most cases (78% of tests), effects on evoked activity were independent of effects on baseline discharge frequency. These data lead to the suggestion that neuropeptides have two influences on septal neurons: a direct, non-synaptic influence on the pacemaker potential responsible for baseline activity, and modulation of synaptic processes. Analysis showed that retention of descending septohippocampal connections was not critical for entry into hibernation and the tonic maintenance of this state. The effects of preoptic-hypothalamic mechanisms of hibernation determine the paradoxical latent excitability of septal cells, allowing the septohippocampal system to filter external signals and provide for urgent arousal of the forebrain during hibernation.

Animals↗

Hippocampus as comparator: role of the two input and two output systems of the hippocampus in selection and registration of information.

Processing of multimodal sensory information by the morphological subdivisions of the hippocampus and its input and output structures was investigated in unanesthetized rabbits by extracellular recording of neuronal activity. Analysis shows principal differences between CA3 neurons with uniform multimodal, mainly inhibitory, rapidly habituating sensory responses, and CA1-subicular neurons, substantial parts of which have phasic reactions and patterned on-responses, depending on the characteristics of the stimuli. These differences result from the organization of the afferent inputs to CA1 and CA3. Analysis of neuronal responses in sources of hippocampal inputs, their electrical stimulation, and chronic disconnection show the greater functional significance of the brain-stem reticular input for tonic responses characteristic of CA3. This input signal before entering the hippocampus is additionally preprocessed at the MS-DB relay, where it becomes more uniform and frequency-modulated in the range of theta-rhythm. It is shown that the new sensory stimuli produce inhibitory reset, after which synchronized theta-modulation is triggered. Other stimuli, appearing at the background of the ongoing theta, do not evoke any responses of the hippocampal neurons. Thus, theta-modulation can be regarded as a mechanism of attention, which prolongs response to a selected stimulus and simultaneously protects its processing against interference. The cortical input of the hippocampus introduces highly differentiated information analyzed at the highest levels of the neocortex through the intermediary of the entorhinal cortex and presubiculum. However, only CA1-subiculum receives this information directly; before its entrance into CA3, it is additionally preprocessed at the FD relay, where the secondary simplification of signals occurs. As a result, CA3 receives by its two inputs (MS-DB and FD) messages just about the presence and level of input signals in each of them, and performs relatively simple functions of determination of match/mismatch of their weights. For this comparator system, the presence of signal only in the reticulo-septal input is equivalent to quality of novelty. The cortical signal appears with some delay, after its analysis in the neocortex and shaping in the prehippocampal structures; besides, it is gradually increased due to LTP-like incremental changes in PP and mossy fiber synapses. The CA3 neurons with potentiated synapses of cortical input do not respond to sensory stimuli; that is, the increased efficacy of the cortical signals can be regarded as "familiarity" of a signal, terminating the reactive state of the CA3 neurons. The integrity of both inputs is necessary for gradual habituation of sensory responses in the hippocampus. The output signals of CA3 following in the precommissural fornix to the output relay-LS nucleus and to the brain-stem structures have strong regulatory influence on the level of brain activity (arousal), which is an important condition for processing and registration of information. The primary targets of this output signal are raphe nuclei, which suppress activity of the ascending excitatory RF. In the background state, activity of the CA3 neurons through the intermediary of raphe keeps RF under tonic inhibitory control. Inhibition of the majority of CA3 pyramidal neurons during a novel stimulus action decreases the volume of its output signal to raphe and releases RF from tonic inhibition (increase in level of activity of the forebrain, arousal). When the responses of CA3 neurons habituate, the initial high background activity is reinstated, as well as tonic suppression of RF. Analysis of the second output of CA3 (by Schaffer's collaterals to CA1) shows that activity in this pathway can block access of cortical signals from PP to CA1 neurons by action upon the local system of inhibitory neurons, or by shunting the propagation of signals in apical dendrites. Thus, CA3 can act as a filter controlling the information transmission by CA1; such transmission at any given moment is allowed only in those CA1 neurons which receive SC from CA3 neurons, responding to the sensory stimulus by suppression of their activity. Disconnection of the CA3 output fibers results in disappearance of habituation in all its target structures (raphe, RF, CA1). The output signal of CA1-subiculum follows by postcommissural fornix to the chain of structures of the main limbic circuit: mammillary bodies (medial nucleus), anterior thalamic nuclei (mainly antero-ventral nucleus), and cingulate limbic cortex (mainly posterior area). In each of these links, the signal is additionally processed. Habituation is nearly absent in these structures; instead, st

Animals↗

State-dependent effects of some neuropeptides and neurotransmitters on neuronal activity of the medial septal area in brain slices of the ground squirrel, Citellus undulatus.

Neuronal activity of the medial septal area was recorded extracellularly in brain slices taken from hibernating (winter) and waking (summer) ground squirrels. The effects of neuropeptides identified in the brain tissue of hibernators (Thr-Ser-Lys-Tyr, Thr-Ser-Lys-Tyr-Arg and Asp-Tyr) on the background activity and responses to electrical stimulation of the median forebrain bundle were analysed. For comparison, the effects of bath application of noradrenaline and serotonin were also tested. Spontaneous activity in half of all neurons (47-56%) was changed under the influence of neuropeptides in hibernating ground squirrels, while in waking ground squirrels the proportion of responsive neurons was significantly lower (25-30%). The tendency for higher efficacy in hibernating ground squirrels was observed for serotonin; only noradrenaline was equally effective in both groups of animals. Electrically evoked responses of the medial septal nucleus-nucleus of the diagonal band neurons were also strongly modulated by neuropeptides; their changes could occur in the absence of shifts in the level and pattern of spontaneous activity. All three neuropeptides had differential action on the level of spontaneous activity, as well as on inhibitory and excitatory components of electrically evoked responses. Thus, the character and distribution of the effects were state dependent and differed greatly in hibernating and waking ground squirrels. The experiments confirmed that medial septal nucleus-nucleus of the diagonal band neurons have higher excitability and responsiveness to some neuropeptides and neurotransmitters in hibernating ground squirrels.The data obtained suggest an increased latent excitability and responsiveness of septal neurons during hibernation and their possible active participation in urgent arousal under the influence of sensory signals.

Action Potentials↗

Spontaneous activity and sensory responses of hippocampal neurons during persistent theta-rhythm evoked by median raphe nucleus blockade in rabbit.

Spontaneous activity and responses to sensory stimuli were analysed in the hippocampal CA1 neurons of chronic unanesthetized rabbits before and after reversible functional blockade of the median raphe nucleus and medial septal area by local microinjections of anesthetic lidocaine. This evoked, correspondingly, persistent theta rhythm and its complete blockade for about 30 min. The results were compared to the neuronal data obtained earlier in the experiments with cholinergic drugs modulating expression of theta rhythm. Intra-median raphe nucleus injection of lidocaine evoked uniform increase of discharge rate in the hippocampal neurons with low and high spontaneous activity. Theta modulation of neuronal activity had increased regularity and frequency (by 0.5-2.0 Hz) and appeared in additional group of the neurons simultaneously with expression of persistent theta in the hippocampal electroencephalogram. Sensory responsiveness of the hippocampal neurons was drastically decreased (45% of the responses preserved). Reactions of all types were blocked, diminished, or inverted, but inhibitory responses were the most severely affected. Injection of lidocaine into medial septal area also blocked all brain stem afferents ascending to the hippocampus via medial septal area, thus, totally depriving hippocampus of brainstem-septal input. However, besides the total absence of theta modulation, spontaneous activity in majority of neurons was not significantly changed. Responsiveness to sensory stimuli also remained relatively high (77% of the responses preserved); on-effects were especially resistant to medial septal area blockade. Comparison of spontaneous and evoked activity in two theta states (physostigmine and median raphe nucleus blockade) revealed striking similarity of all characteristics, which suggested that theta-suppressing influences of median raphe nucleus (presumably serotonergic) are realized primarily through the control of cholinergic septo-hippocampal theta-generating mechanism. However, as the frequency of theta rhythm does not depend on it, an additional effect of disinhibition of activating reticular formation by the median raphe nucleus suppression is suggested. The data confirm that theta rhythm may be regarded as active filter in the information processing by the hippocampal neurons.

Afferent Pathways↗

Neuronal activity of the septal pacemaker of theta rhythm under the influence of stimulation and blockade of the median raphe nucleus in the awake rabbit.

The control of theta rhythm in neuronal activity of the medial septal area and hippocampal electroencephalogram by the brainstem structures was investigated in waking rabbits. In the first series of experiments stimulating electrodes were implanted into the midbrain reticular formation and median raphe nucleus. The standard frequency of theta-bursts in medial septal area neurons and in the electroencephalogram was uniformly and chronically decreased in all rabbits with electrodes implanted into the median raphe nucleus (4.7 +/- 0.5 Hz versus 5.2 +/- 0.19 Hz in animals without electrodes in median raphe nucleus). Weak electrical stimulation of the median raphe nucleus resulted in additional decrease of theta expression in the medial septal area neurons and its disappearance from the hippocampal electroencephalogram, where it was substituted by delta-waves and spindles. Stimulation of the reticular formation had the opposite effect, with an increase in theta frequency, regularity and expression in medial septal area neuronal activity and hippocampal electroencephalogram. In the second series of experiments reversible functional blockade of the median raphe nucleus by local microinjection of lidocaine was performed. This resulted in expression of theta-bursts in an additional group of medial septal area neurons, an increase in theta-burst frequency (by 0.5-2 Hz) and regularity with concomitant changes in the electroencephalogram. The effects of sensory stimuli on the background of increased theta activity were suppressed or significantly decreased. It is concluded that, in accordance with the data of other authors, the median raphe nucleus can be regarded as a functional antagonist of the reticular formation, powerfully suppressing theta-bursts of the medial septal area neurons and hippocampal theta rhythm. It is suggested that, in combination with the theta-enhancing influences of reticular formation, the median raphe nucleus may participate in termination of attention, its switching to other stimuli and stabilization of the effects of learning.

Animals↗

Pacemaker neurons of the forebrain medical septal area and theta rhythm of the hippocampus.

The hippocampus is of critical importance for the organization of selective attention and memory. The activity of its neurons is rhythmically modulated by the direct afferent input from cholinergic and GABAergic neurons of the medial septal nucleus and the nucleus of diagonal band (MS-DB). This modulation is expressed in the hippocampal electroencephalogram as a slow (4-9 Hz) sinusoidal theta rhythm. The paper presents a short review of the authors' data on the properties of MS-DB cells, their interactions in organizing the theta expression in the hippocampus, and the probable functional significance of this rhythm. Extracellular recordings of neural activity of the MS-DB and hippocampus were performed in chronic alert rabbits with transection of various afferent pathways, in brain slices, and in the embryonic tissue grafts developing in the anterior eye chamber and brain. Theta modulation disappeared in all structures deprived of the MS-DB afferent connections, but was retained by MS-DB neurons under isolation conditions. A limited group of MS-DB neurons (6-8%) discharge in regular bursts after complete synaptic blockade in high Mg(2+)-low Ca2+ medium, while other neurons in these conditions exhibited the highly regular single-spike activity. Thus, the MS-DB neurons can be regarded as bursting and regular pacemakers. The frequency of bursts and the number of neurons involved in the rhythmic activity are in parallel increased by afferent stimulation-either natural (sensory stimuli) or imitated by electrical stimulation of ascending reticular formation. An increase in the number of MS-DB neurons secondarily involved in theta bursts with the resulting expression of theta rhythm in EEG can be also obtained by up-regulation of endogenous acetylcholine (by physostigmine), but in this case the frequency of theta is not changed. The MS-DB neurons contain acetylcholine and GABA as neurotransmitters. Analysis of the effects of their agonists and antagonists suggests that the frequency of theta depends on the GABAergic mechanism, while its power is controlled by cholinergic influences. In the control state, input signals triggered in the hippocampal neurons an inhibitory reset followed by synchronous theta modulation, gradually habituating during repeated presentations of the stimulus. Against the background of continuous theta evoked by physostigmine, the responses were blocked or significantly depressed, while after theta suppression by scopolamine the efficacy of the stimuli was increased, and habituation was absent. It is suggested that the theta rhythm operates as a selective filter: it augments and prolongs the input signal by which it was triggered and simultaneously protects it from the interference of extraneous stimuli appearing during its processing and registration. The theta rhythm may be regarded as an important mechanism of selective attention, which is a prerequisite for memory trace formation.

Animals↗

Expression, control, and probable functional significance of the neuronal theta-rhythm.

The data on theta-modulation of neuronal activity in the hippocampus and related structures, obtained by the author and her colleagues have been reviewed. Analysis of extracellularly recorded neuronal activity in alert rabbits, intact and after various brain lesions, in slices and transplants of the hippocampus and septum allow one to make the following conclusions. Integrity of the medial septal area (MS-DB) and its efferent connections are indispensable for theta-modulation of neuronal activity and EEG of the hippocampus. The expression of hippocampal theta depends on the proportion of the MS-DB cells involved in the rhythmic process, and its frequency in the whole theta-range, is determined by the corresponding frequencies of theta-burst in the MS-DB. The neurons of the MS-DB have the properties of endogenous rhythmic burst and regular single spike oscillators. Input signals ascending to the MS-DB from the pontomesencephalic reticular formation increase both the frequency of the MS-DB theta-bursts and the proportion of neurons involved in theta-activity; serotonergic midbrain raphe nuclei have the opposite effect on the MS-DB rhythmic activity and hippocampal EEG theta. Increase of endogenous acetylcholine (by physostigmine) also increases the proportion of the MS-DB neurons discharging in theta-bursts (both in intact and basally-undercut septum), but does not influence the theta-frequency. The primary effect of the MS-DB on hippocampal neurons (pyramidal and non-pyramidal) consists in GABAergic reset inhibition. Reset inhibition, after which theta-modulation follows in constant phase relation, is triggered also by sensory stimuli. About two-thirds of the hippocampal pyramidal neurons are tonically inhibited by sensory stimuli which evoke EEG theta, while others are excited, or do not change their activity. Anticholinergic drugs restrict the population of rhythmic neurons but do not completely suppress theta-bursts in the MS-DB and hippocampus. Under their action, EEG theta can be evoked (presumably through GABAergic MS-DB influences) by strong reticular or sensory stimuli with corresponding high frequency. However information processing in this condition is defective: expression of reset is increased, responses to electrical stimulation of the perforant path and to sensory stimuli are often augmented, habituation to sensory stimuli is absent and tonic responses are curtailed. On a background of continuous theta induced by increase of endogenous acetylcholine, reset is absent or reduced, responsiveness of the hippocampal neurons to electrical and sensory stimulation is strongly reduced.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Integration of hippocampal suspension grafts with host neocortex.

The possibility of histological and functional integration of nervous tissue heterotopically grafted into the adult host brain was investigated. Suspensions of embryonic (E17-18) rat hippocampus with dentate fascia were placed into acute cavities in the barrel field of young adult rats (n = 25). Golgi-Cox silver impregnation and Cresyl Violet stain were used for histological analysis 3-4 months postgrafting. The surviving grafts were present in 80% of the grafted animals. Only three out of 20 surviving grafts were completely isolated from the surrounding host brain; other grafts had areas of direct confluence with the host neuropil. Extracellular recording of neuronal activity revealed normal spontaneous activity typical of the hippocampus in the majority of the grafts. Electrical stimulation of the posterior nucleus of the thalamus, homolateral motor neocortex, contralateral barrel field, and sensory stimulation of the host evoked responses in 50-60% of the grafted neurons. This did not differ significantly from the responsiveness of the similarly tested neurons of homotopic neocortical suspension grafts. The latencies of the responses in the hippocampal grafts were consistently longer (by about 10 ms) than in the neocortical ones. Comparison of the hippocampal suspension grafts with other types of hippocampal and neocortical grafts suggests that under certain conditions heterotopic tissue can be successfully integrated into the host brain. Development of the host-graft interconnections depends on topical proximity, the presence of denervated synaptic loci in both tissues, elimination of the intragraft neuronal targets and disruption of the intrinsic connections between them.

Animals↗

Acetylcholine, theta-rhythm and activity of hippocampal neurons in the rabbit--I. Spontaneous activity.

The background activity of hippocampal neurons was recorded extracellularly in waking rabbits in the control state and after systemic injections of physostigmine and scopolamine. Similar analysis was done in the hippocampus chronically deprived of ascending brainstem afferents. Cholinergic drugs control the number of hippocampal neurons with theta modulation and stability, but not the frequency of theta modulation. Increase of endogenous acetylcholine also resulted in regularization of the activity with suppression of delta modulation and complex spike discharges; its blockade produced the opposite changes. Both drugs changed the level of background activity in the majority of the neurons, but the overall mean frequency did not vary between the states. Regression analysis demonstrated significant negative correlations with dominating decrease in the level of discharges in high-frequency neurons (> 25 spikes/s) and its increase in low-frequency ones (< 25 spikes/s) after injection of both drugs. Stability of the overall mean frequency and uniformity of its shifts during both stimulation and suppression of the cholinergic component of theta-rhythm presumably indicate that the frequency of background activity, unlike its pattern, is not directly controlled by the cholinergic septal input.

Acetylcholine↗

Acetylcholine, theta-rhythm and activity of hippocampal neurons in the rabbit--II. Septal input.

The aim of this paper was to evaluate the cholinergic component of the septohippocampal input signals in neuronal activity of the hippocampal fields CA1 and CA3 recorded extracellularly in chronic alert rabbits. Effects of electrical stimulation of the medial septal area were analysed in the control state, on the background of an increased level of endogenous acetylcholine (by physostigmine injection) and during its blockade by antimuscarinic drugs (scopolamine, atropine). Two groups of animals were used in the experiments: intact rabbits and rabbits with complete chronic undercutting of the septum, depriving the septohippocampal system of ascending medial forebrain bundle afferents. Primary inhibitory effects of standard duration (40-140 ms) evoked by medial septal area stimulation dominated in the hippocampus of intact rabbits (54%), though some neurons responded by initial diffuse excitation (37.5%); responses by single-spike on-effects were observed in a minority of neurons (8.5%). The primary suppression of activity prevailed (90%) in animals with basal undercutting of the septum. In intact rabbits under physostigmine action, the effects of medial septal area stimulation were depressed or completely blocked in 78% of hippocampal neurons on the background of increased theta modulation of activity. Neuronal responses to medial septal area stimulation recovered at the background of muscarinic antagonists. These effects of cholinergic drugs were reproduced in animals without medial forebrain bundle. It is concluded that the initial effect of the septal input upon the hippocampal neurons consists of a general suppression of their activity (reset), depending upon a non-cholinergic (presumably GABAergic) component of the septohippocampal connections.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

Acetylcholine, theta-rhythm and activity of hippocampal neurons in the rabbit--III. Cortical input.

Cholinergic modulation of single cell responses and field potentials evoked in the hippocampus by electrical stimulation of the perforant path and mossy fibres was investigated in two groups of chronic unanesthetized rabbits--with intact hippocampus and with basally undercut septum (without ascending medial forebrain bundle afferents). In both groups of animals responses to stimulation were blocked or significantly depressed by i.v. physostigmine injection in many neurons (50% in the intact hippocampus and 69% in the hippocampus without medial forebrain bundle). In minor groups of neurons (10 and 8%, respectively), facilitation of responses was observed. Scopolamine restored initial responsiveness of hippocampal neurons and augmented effects of stimulation in some of them. The effect of physostigmine was reproduced by stimulation of the medial septum. Depressive influence of medial septal area stimulation was increased by physostigmine and blocked by scopolamine. Population spikes evoked by stimulation of the perforant path of the intact group were equally suppressed (by 43%) during sensory stimulation evoking natural theta, after physostigmine and after medial septal area stimulation. In the group of animals without medial forebrain bundle these influences resulted in a complete suppression of field potentials; scopolamine restored them. It is concluded that the main function of the septohippocampal cholinergic input consists of filtering out the signals appearing at the background of theta-rhythm triggered by a previous signal, thus preventing their interference with its processing and registration.

Acetylcholine↗

Acetylcholine, theta-rhythm and activity of hippocampal neurons in the rabbit--IV. Sensory stimulation.

Modifications of responses of hippocampal neurons to sensory stimuli at the background of increased endogenous acetylcholine level (injection of physostigmine) and during blocking by scopolamine were analysed in the chronic alert rabbit. A significant decrease of reactivity (about 40%) of hippocampal neurons to sensory stimuli occurred after physostigmine injection, inducing stable theta modulation. Suppression and decrease of inhibitory responses (including initial reset phase) and of some excitatory reactions (including on-effects) were observed. However, a limited group of excitatory responses was augmented and prolonged under physostigmine action. Scopolamine, which blocked electroencephalogram theta-rhythm, did not change the responsiveness of hippocampal neurons. Some of the inhibitory and excitatory effects of sensory stimuli, especially on-responses, were strongly facilitated. Tonic responses were shorter, but they were stably reproduced without typical gradual habituation. All these effects were also present in the hippocampus after basal undercutting of the septum, which eliminates ascending brainstem input. It is suggested that under normal conditions a new or significant sensory stimulus evokes, in the hippocampus, an initial inhibitory reset of neuronal activity with subsequent coordinated triggering of rhythmic theta modulation by the septal input and arrival of the cortical input signal phase-locked to it. During the period of theta triggered by the stimulus, its processing and fixation in memory occurs, while the other, interfering stimuli, which are not phase-locked to the ongoing theta activity, are actively filtered out. Thus, septohippocampal interactions may participate in the organization of selective attention as a necessary condition for memory trace formation.

Acetylcholine↗

Paradoxical state-dependent excitability of the medial septal neurons in brain slices of ground squirrel, Citellus undulatus.

Spontaneous and evoked neuronal activity of the medial septum-diagonal band complex was investigated extracellularly in slices, taken from the brain of the three groups of animals: hibernating ground squirrels, waking ground squirrels, and guinea-pigs. All slices were incubated at 31-32 degrees C. The slices of the ground squirrels' brain were retested after keeping them for 15-36 h in the refrigerator at 2-4 degrees C. In all experimental groups the majority of the medial septum-diagonal band complex neurons had high regular or rhythmic burst spontaneous activity, which in half of the neuronal population persisted in conditions of synaptic blockade. The low-frequency irregular activity of the surrounding structures (lateral septum, caudate, accumbens, medial preoptic area) was completely suppressed in these conditions. The density of the spontaneously active neurons in the slices, as well as the mean frequency of discharges in the medial septum-diagonal band complex of hibernating ground squirrels, was significantly higher than that in waking ground squirrels and guinea-pigs. Stimulation of the medial forebrain bundle evoked initial suppression of activity in majority of the medial septum-diagonal band complex units; in many of them the suppression was followed by a burst discharge. The neurons with background rhythmic burst activity always responded by resetting the spontaneous bursts. In total, about 50-60% of the medial septum-diagonal band complex neurons of waking ground squirrels and guinea-pigs responded by post inhibitory bursts to the stimulation of medial forebrain bundle, while in hibernating ground squirrels such responses were observed in nearly all neurons. The threshold values of the stimulating current were significantly lower in the hibernating ground squirrels' group, the mean duration of the initial suppression was shorter, the intraburst density of spikes and/or duration of the bursts was increased. Thus, evaluation of spontaneous and evoked activity on the basis of various criteria revealed surprising similarity between the two groups of active animals, while the activity and excitability of the medial septum-diagonal band complex neurons was approximately doubled in the hibernating animals. This difference between active and hibernating ground squirrels was preserved during retesting after deep and prolonged cooling of the slices. The experiments demonstrate paradoxical stable increase of activity and excitability of the medial septum-diagonal band complex neurons in the hibernating ground squirrels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Growth of the hippocampal grafts in the rat anterior eye chamber: effects of age and strain of the recipients.

Hippocampal tissue (1 mm3) was taken from embryonal (E17-18) rats of Wistar stock in population breeding and grafted into anterior eye chamber of the four groups of recipients: young (3 weeks) and old (18 months) males of the same stock and of inbred strain WAG. Morphometric analysis of the grafts developing up to 12 weeks in oculo showed rapid initial growth in both groups of the young hosts during the first three weeks, and limited increase of the graft volume during next three weeks. The start of growth was significantly retarded in the old hosts, but this was partly compensated by prolonged increase of the graft volume during the later stages. Both mean and maximal finite volume were much smaller in both WAG groups. The hippocampal grafts in these groups had rounded (not elongated, as in Wistar groups) shape and showed tendency to fragmentation and resorbtion at the late stages. Histological analysis revealed well organized layer of the pyramidal cells in the both Wistar groups and nearly complete absence of neuronal organization into layer in both WAG groups. Possible role of trophic and immune factors in development of intraocular grafts is discussed.

Aging↗

Functional integration of the rat hippocampal tissue, transplanted into the rabbit septum.

Embryonal tissue of the rat hippocampus (E17-18) was grafted into small acute cavity within the dorsal septum of adult rabbit after interruption of septo-hippocampal connections. Histological analysis (Nissl stain), performed 6-8 weeks later, revealed surviving hippocampal grafts in 14 out of 29 grafted animals (48%). Some of the grafts were displaced into the ventricle and had only minor contact with the host septum; some others, residing in the septum, were separated from the host tissue by continuous glial scar. Six grafts (33%) were morphologically well integrated with the host septum. The grafts contained mature pyramidal neurons but their organization into layer was absent. No signs of rejection were observed in the grafts, which were not subjected to microelectrode investigation in chronic conditions. The grafts, which for 5-9 successive days were penetrated by microelectrodes, were heavily infiltrated by lymphocytes and had necrotic areas. Electrophysiological testing revealed the absence of spontaneous neuronal activity, or the presence of hypersynchronous epileptiform bursts in isolated grafts. The 4 integrated grafts, investigated electrophysiologically, contained neurons with normal spontaneous activity of two types: low-frequency discharges with complex spikes and high-frequency single spikes, sometimes with short periods of weak rhythmic modulation in the theta-range. Characteristics of spontaneous activity of the xenografted hippocampus are very close to those described in the rat hippocampus in situ. Rhythmic theta-modulation of neuronal activity appeared or increased in stability after physostigmine injection to the host, after electrical stimulation of the host's midbrain reticular formation and ventral part of diagonal band, and after multimodal sensory stimulation of the host. The frequency of theta-bursts in the grafts was identical to that of neurons of the host septum (4.5-6.5 Hz). Besides the theta-modulation sensory stimuli evoked tonic suppression or activation of discharges, phasic reactions and on-effects. Electrical stimulation of lateral septum and diagonal band evoked orthodromic and antidromic discharges of the grafted cells. Normal spontaneous and evoked activity of the grafted cells deteriorated after 5-11 successive days of microelectrode investigation. It is concluded that xenografts of nervous tissue, developing without immunosuppression, have a low rate of survival and are vulnerable to immune response after mechanical interruption of integrity of the blood-brain barrier. Nevertheless their normal activity and close functional integration with the host brain, apparently depending on development of chimeric synapses, is possible.

Action Potentials↗

Some unusual characteristics of the nucleus anterodorsali thalami: neurophysiological and ultrastructural investigation.

Single-unit activity and ultrastructural characteristics were investigated in anterodorsal nucleus of thalamus (AD) in rabbits, guinea pigs and rats. Spontaneous activity of the AD units consisted of long high-frequency trains of spikes alternating with prolonged periods of silence. The typical thalamic "inactivation bursts" were never observed in AD. The AD neurons were highly reactive to sensory stimuli of various modalities. The stimuli evoked sustained discharges with or without initial short-latency on-effects. The AD neurons in incubated slices responded to electrical stimulation of afferent inputs by high-frequency sustained discharges (up to several s). The neurons had long period of facilitation, which allowed summation of effects of repetitive stimuli following with intervals up to 20-30 s, and equally long refractory periods after tonic discharge. Ultrastructural investigation revealed highly developed Nissl bodies and extensive multilocular Golgi complex in large AD neurons. Specialized standard combinations of elements of rough and smooth endoplasmic reticulum ("doublets") were widely distributed in their cytoplasm. Large aggregates of finely granular or filamentous material (nematosomes) were present in AD neurons. The perivascular glial endfeet in some areas of the AD were very thin or absent altogether, with direct apposition of neuronal somata to the capillary basal membrane, which was characterized by high pinocytotic activity. All functional and structural features of AD listed above were absent in adjacent anteroventral nucleus. It is suggested that the AD neurons possibly have some specialized neurosecretory activity, which, regarding the role of this nucleus in relaying multimodal sensory information to the highest levels of limbic system (hippocampal formation and retrosplenial cortex), may have some special significance for memory functions.

Action Potentials↗