RESUMEN
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.
Asunto(s)
Hibernación/fisiología , Neuronas/efectos de los fármacos , Neuropéptidos/farmacología , Norepinefrina/farmacología , Área Preóptica/fisiología , Núcleos Septales/efectos de los fármacos , Serotonina/farmacología , Animales , Estimulación Eléctrica , Endorfinas/farmacología , Técnicas In Vitro , Neuronas/fisiología , Fragmentos de Péptidos/farmacología , Sciuridae , Núcleos Septales/citología , Núcleos Septales/fisiologíaRESUMEN
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.
Asunto(s)
Endorfinas/farmacología , Hibernación/fisiología , Área Preóptica/citología , Sciuridae/fisiología , Núcleos Septales/citología , Núcleos Septales/fisiología , Potenciales de Acción/efectos de los fármacos , Potenciales de Acción/fisiología , Animales , Desnervación , Estimulación Eléctrica , Potenciales Evocados/efectos de los fármacos , Neuronas/metabolismo , Norepinefrina/farmacología , Técnicas de Cultivo de Órganos , Fragmentos de Péptidos/farmacología , Serotonina/farmacología , Simpatomiméticos/farmacologíaRESUMEN
Effects of some neuropeptides identified in the brain of hibernators (TSKYR, TSKY, DY) and of monoaminergic neurotransmitters (noradrenaline and serotonin) on responses of the medial septal neurons evoked by intraseptal electrical stimulation were analyzed in slices taken from the ground squirrels with chronic basal undercutting of the septum. Despite the elimination of direct contacts with the preoptic area and afferents ascending in the medial forebrain bundle, the neurons retained almost normal level of reactivity and distribution of the reaction types. The neuropeptides effectively modulated neuronal responses of various types, including oligosynaptic short-latency single-spike responses. The latter were strongly facilitated by the neuropeptides. As a rule, changes in the responses to electrical stimulation were independent of the spontaneous activity shifts (in 78% of the tests). It was suggested that the neuropeptides exert a double influence on the septal neurons: direct nonsynaptic effects on the pacemaker potential responsible for the background activity and modulation of synaptic processes. Our experiments showed that descending influences of the septo-hippocampal system are not crucial for the entrance into the hibernation state and its tonic maintenance. The influences of the thermoregulatory--circadian structures of the preoptico-hypothalamic area determine the paradoxically increased latent excitability of septal neurons that allows the septo-hippocampal system to gate external stimuli and organize arousal of the forebrain during hibernation in case of emergency.
Asunto(s)
Endorfinas/farmacología , Hibernación/fisiología , Neuronas/fisiología , Fragmentos de Péptidos/farmacología , Sciuridae/fisiología , Núcleos Septales/fisiología , Animales , Estimulación Eléctrica , Potenciales Evocados , Hipotálamo/fisiología , Técnicas In Vitro , Neurotransmisores/farmacología , Norepinefrina/farmacología , Núcleos Septales/efectos de los fármacos , Serotonina/farmacología , Techo del Mesencéfalo/fisiologíaRESUMEN
Our previous work demonstrated paradoxically increased excitability of the medial septal (MS) neurons during hibernation of ground squirrels in comparison to waking animals. Recently this was supported by demonstration of higher efficacy of the neuropeptides identified in the brain of hibernators in septal slices of hibernating animals. To decide whether this increased excitability is determined by endogenous properties of the pacemaker septal neurons, or it depends on the influences of thermoregulatory-circadian mechanisms of preoptico-hypothalamic area, testing of the neuropeptides (TSKYR, TSKY, DY) and neurotransmitters participating in control of hibernation (serotonin and noradrenaline) was repeated on septal slices taken from the brain of hibernating animals two weeks after operation disconnecting it from the hypothalamus. Effects of neuropeptides in the deafferented hibernating animals neither quantitatively (low reactivity level), nor qualitatively (distribution of inhibitory and excitatory responses) differed from the data obtained in waking animals. Decrease of reactivity occurred at the expense of the neurons with regular pacemaker-like spontaneous activity. Thus, increased reactivity of the MS neurons to neuropeptides in hibernating animals depends mainly on influence of the hypothalamic centres controlling hibernation behavior upon pacemaker neurons of the MS. Contrary to the neuropeptides, serotonin and noradrenaline were highly effective in deafferented septum. They evoked stronger changes of background activity (shorter latencies and more rapid development of maximal shifts), presumably as a result of development of denervation hypersensitivity after deafferentation.
Asunto(s)
Hibernación/fisiología , Hipotálamo/fisiología , Neuronas/fisiología , Sciuridae/fisiología , Tabique del Cerebro/fisiología , Animales , Neuropéptidos/fisiologíaRESUMEN
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
Asunto(s)
Corteza Cerebral/citología , Hipocampo/citología , Hipocampo/fisiología , Animales , Atención/fisiología , Habituación Psicofisiológica/fisiología , Memoria/fisiología , Vías Nerviosas , ConejosRESUMEN
Evoked neuron activity in slices of the medial septal area and its modulation by neuropeptides and monoamines was studied in two groups of ground squirrels--hibernating and awake animals. Electrical stimulation of the medial forebrain bundle evoked predominantly inhibitory effects of different durations. In addition, responses were seen consisting of resetting of the phase of background volleys to the stimulus after initial inhibition: there were also small numbers of short-latency single-spike responses. All the neuropeptides tested. which had been identified from the brains of hibernating animals, induced differentiated reversible effects consisting of modulation of responses; changes in evoked activity were seen significantly more often than shifts in spontaneous activity. The effects depended on the state of the animal. Thus. peptide TSKYR increased the duration of inhibition in hibernating ground squirrels but shortened inhibition in awake animals. Peptide TSKY. which had little effect in hibernating animals, increased the duration of inhibition in awake animals. Dipeptide DY. which decreased the duration of inhibition and increased the amplitude of the activatory components of responses in hibernating ground squirrels. had little effect in awake animals. The effects of noradrenaline and serotonin correlated to a large extent with their effects on spontaneous activity. It is suggested that endogenous substances are involved in creating the conditions required for increasing the latent excitability and reactivity of septal neurons during hibernation. This allows the medial septal area to function as a "sentry post," allowing the receipt of signals and urgent arousal during hibernation.
Asunto(s)
Hibernación/fisiología , Neuronas Aferentes/fisiología , Neuronas/fisiología , Sciuridae/fisiología , Tabique del Cerebro/fisiología , Animales , Diencéfalo/citología , Diencéfalo/fisiología , Estimulación Eléctrica , Potenciales Evocados/efectos de los fármacos , Neuropéptidos/farmacología , Norepinefrina/farmacología , Serotonina/farmacología , Simpatomiméticos/farmacologíaRESUMEN
The new neuroscience data rapidly accumulating by the end of the second millennium calls for radical revision of many long-established and widely accepted postulates. This paper reviews some data leading to new concepts of life and work of neurons. The adult brain contains stem cells which are the source of the precursors for all main types of the brain cells: neurons, astrocytes, and oligodendroglia. These cells can substitute the deteriorating elements in the adult and even old brain. The neurons occur to be highly resistant to lesion of their processes as well to anoxia, and inhibitory neurons are shown to be especially stable in some pathological conditions. Changes in the afferent inputs result in various types of rapid compensatory morphological and functional reorganizations at different levels. Thus, the previous fatalistic view of the nervous system is substituted now for an optimistic one regarding various possibilities of prolongation and restoration of normal functioning of the brain. Simultaneously, our concepts of the neurons changed drastically. An unitary neuron may operate by several neurotransmitting substances; their synaptic influences upon the dendrites may evoke the active propagation of calcium and sodium spikes, their axons may differentially release transmitter substances depending on parameters of excitation. All neuronal functions are helped and controlled by astroglia, which participates in the synthesis of transmitters and protects the neurons from the excitotoxic death. Besides the synaptic interactions between the neurons, there exist other types of communications, such as volume conduction of transmitters after their spillover from the excited synapses and non-synaptic (varicose) zones, as well as exchange of molecules and ions through the gap junctions. A complex picture of interneuronal communications with multiple synaptic, presynaptic, and parasynaptic interactions is further complicated by the intimate participation of neurotrophic substances and "mediators of the immune system"--cytokines in these processes. The mutual regulatory influences between neurotransmitters, neurotrophic, and neuroimmune systems show that in normal conditions all they are working in concert. This increase in number of factors determining the final result of interaction between the neurons contributes new difficulties to the development of theoretical concepts or simulation of brain functions. In this context it is possible to speak about a certain crisis of theoretical neurobiology at present, because multiplicity of fine details obtained by molecular neurobiology and neurogenetics cannot be integrated in a coherent view of the brain functions. Overcoming the present gap between the analytic and synthetic approaches to understanding the brain work will be the main aim for the neurobiologists of the third millennium.
Asunto(s)
Neurociencias/tendencias , Animales , Encéfalo/fisiología , Muerte Celular/fisiología , Electrofisiología , Humanos , Neuronas/fisiología , Neurotransmisores/fisiologíaRESUMEN
Responses of the medial septal (MS-DB) neurons to electrical stimulation of the medial forebrain bundle (MFB) and their modulation by some neuropeptides and monoamines were investigated in brain slices taken from two groups of ground squirrels-hibernating (HGS) and waking (WGS). Electrical stimulation evoked mostly inhibitory effects of various duration. Besides, responses by phase reset of the background rhythmic bursts and short-latency single spike responses were observed. The neuropeptides identified in the brain of hibernators differentially and reversibly modulated responses even in those neurons where they did not influence the level and pattern of the background activity. Effects of the peptides were state-dependent. E.g., the peptide TSKYR increased the duration of inhibitory effects in the HGS but shortened them in the WGS, while TSKY which had low efficacy in the HGS, increased the duration of inhibition in the WGS. Dipeptide DY depressed inhibitory components and augmented excitatory components of responses in the HGS but was much less effective in the WGS. Effects of noradrenaline and serotonin had stronger correlation with their influence on spontaneous activity. It is suggested that endogenous substances provide for the increased latent excitability and reactivity of the MS-DB neurons during seasonal hibernation. Thus, the MS-DB may function as a "sentry post" participating in signal detection and urgent arousal during hibernation.
Asunto(s)
Vías Aferentes/fisiología , Hibernación , Neuronas/fisiología , Tabique del Cerebro/fisiología , Animales , Dipéptidos/farmacología , Estimulación Eléctrica , Endorfinas/farmacología , Norepinefrina/farmacología , Fragmentos de Péptidos/farmacología , Sciuridae , Tabique del Cerebro/citología , Serotonina/farmacología , VigiliaRESUMEN
Neuronal activity of the medial septal area (MS-DB) was recorded extracellularly in brain slices from two groups of Yakutian ground squirrels Citellus undulatus--hibernating (winter period) and actively waking (summer period). Effects of three neuropeptides identified in the brain of hibernators (TSKYR, TSKY, and DY) and of two monoamines (serotonin and noradrenaline) on spontaneous activity were analyzed. All neuropeptides reversibly changed the levels of the background activity, but in the hibernating ground squirrels (HGS) the level of reactivity (47-56%) was significantly higher than in the waking ground squirrels (WGS, 25-30%). Serotonin also showed some tendency to higher efficacy in the HGS. Only noradrenaline was equally effective and had absolutely dominating excitatory effect in both states, although the level of excitation in the HGS was higher. All other substances evoked excitatory and inhibitory effects in various proportions. Their distribution was state-dependent, the rate of development, intensity and duration of the effects were greater in the HGS. The experiments confirmed the data on higher excitability and reactivity of the septal neurons in the state of hibernation. It is suggested that the tested neuropeptides may participate in the control of hibernation.
Asunto(s)
Monoaminas Biogénicas/farmacología , Hibernación/efectos de los fármacos , Neuronas/efectos de los fármacos , Neuropéptidos/farmacología , Tabique del Cerebro/efectos de los fármacos , Animales , Dipéptidos/farmacología , Endorfinas/farmacología , Hibernación/fisiología , Microelectrodos , Neuronas/fisiología , Norepinefrina/farmacología , Fragmentos de Péptidos/farmacología , Sciuridae , Estaciones del Año , Tabique del Cerebro/fisiología , Serotonina/farmacología , EstereoisomerismoRESUMEN
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.
Asunto(s)
Hibernación/efectos de los fármacos , Hibernación/fisiología , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Neuropéptidos/metabolismo , Neuropéptidos/farmacología , Neurotransmisores/metabolismo , Neurotransmisores/farmacología , Sciuridae/anatomía & histología , Sciuridae/metabolismo , Núcleos Septales/efectos de los fármacos , Núcleos Septales/metabolismo , Potenciales de Acción/efectos de los fármacos , Potenciales de Acción/fisiología , Agonistas alfa-Adrenérgicos/metabolismo , Agonistas alfa-Adrenérgicos/farmacología , Animales , Potenciales Evocados/efectos de los fármacos , Potenciales Evocados/fisiología , Técnicas In Vitro , Neuronas/citología , Norepinefrina/metabolismo , Norepinefrina/farmacología , Núcleos Septales/citología , Serotonina/metabolismo , Serotonina/farmacologíaRESUMEN
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.
Asunto(s)
Hipocampo/fisiología , Neuronas/fisiología , Fisostigmina/farmacología , Núcleos del Rafe/fisiología , Escopolamina/farmacología , Ritmo Teta/efectos de los fármacos , Vías Aferentes/fisiología , Animales , Tronco Encefálico/efectos de los fármacos , Tronco Encefálico/fisiología , Estimulación Eléctrica , Electroencefalografía/efectos de los fármacos , Hipocampo/efectos de los fármacos , Lidocaína/farmacología , Neuronas/efectos de los fármacos , Conejos , Núcleos del Rafe/efectos de los fármacos , Tabique del Cerebro/fisiologíaRESUMEN
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.
Asunto(s)
Lidocaína/farmacología , Neuronas/fisiología , Núcleos del Rafe/fisiología , Núcleos Septales/fisiología , Ritmo Teta , Animales , Estimulación Eléctrica , Electroencefalografía/efectos de los fármacos , Lidocaína/administración & dosificación , Microinyecciones , Conejos , Núcleos del Rafe/efectos de los fármacos , Formación Reticular/fisiología , Ritmo Teta/efectos de los fármacosRESUMEN
The functional importance of theta modulation in the activity of hippocampal neurons was further analyzed using a method consisting of controlled sequential short-term (25-30 min) inclusion or exclusion of the theta rhythm by local administration of lidocaine into the median cervical nucleus and medial septal region respectively. Studies were carried out using conscious rabbits with extracellular recording of hippocampal neuron activity in field CA1. Administration of lidocaine into the medial septal nucleus and diagonal tract nucleus (MS-DT) led to complete inhibition of theta modulation in neuronal and total hippocampus activity. The mean frequency of background discharges underwent no change in most neurons, but decreased significantly in a limited group of cells with high-frequency activity (presumptive inhibitory neurons). Administration of lidocaine into the median cervical nucleus (MCN), the source of serotoninergic pathways to the MS-DT and hippocampus, was accompanied by increases in the stability and frequency of theta modulation of neuronal activity, induction of theta modulation in an additional group of neurons, and expression of a continuous theta rhythm in the electrical activity (EA) of the hippocampus. The mean frequency and regularity of discharges increased in most cells. These data support the existence of tonic inhibitory effects on the part of the MCN on the septa-hippocampal system generating the theta rhythm; in this regard, the MCN can be regarded as an antagonist of the activating reticular formation.
Asunto(s)
Hipocampo/fisiología , Neuronas/fisiología , Ritmo Teta , Anestésicos Locales/administración & dosificación , Anestésicos Locales/farmacología , Animales , Estimulación Eléctrica , Electrofisiología , Hipocampo/citología , Lidocaína/administración & dosificación , Lidocaína/farmacología , Potenciales de la Membrana/fisiología , Microelectrodos , Microinyecciones , Estimulación Física , ConejosRESUMEN
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.
Asunto(s)
Hipocampo/fisiología , Neuronas/fisiología , Prosencéfalo/fisiología , Animales , Electroencefalografía , Hipocampo/citología , Prosencéfalo/citología , ConejosRESUMEN
A method of controlled successive short-term (25-30 min) stabilization or suppression of the theta rhythm by local injections of lidocaine into median raphe nucleus or medical septal area (MS-DB) was tested for further analysis of the functional significance of theta-modulation in activity of hippocampal neurons. Extracellular recording of their activity (area CAl) was performed in unanaesthetized rabbits. Injection of lidocaine into MS-DS resulted in total suppression of theta modulation in neuronal activity and EEG of the hippocampus. Mean frequency of the background activity was not changed in the majority of the units but was significantly increased in a limited group of high-frequency neurons (putative inhibitory cells). Injection into medial raphe, the source of serotonergic afferents to MS-DB and hippocampus, was followed by an increase in regularity and frequency of theta modulation, by appearance of additional group of neurons with rhythmic modulation, and by expression of continuous theta in the hippocampal EEG. Mean frequency of discharge and its regularity were significantly increased in the majority of the cells. The data confirm the presence of tonic inhibitory control of theta-generating septo-hippocampal system by the medial raphe nucleus, which can be regarded as an antagonist of the midbrain reticular formation in this respect.
Asunto(s)
Hipocampo/fisiología , Neuronas/fisiología , Ritmo Teta , Anestésicos Locales/administración & dosificación , Anestésicos Locales/farmacología , Animales , Depresión Química , Electrodos Implantados , Hipocampo/efectos de los fármacos , Lidocaína/administración & dosificación , Lidocaína/farmacología , Microelectrodos , Microinyecciones/métodos , Neuronas/efectos de los fármacos , Conejos , Procesamiento de Señales Asistido por Computador/instrumentación , Ritmo Teta/efectos de los fármacos , Ritmo Teta/instrumentación , Ritmo Teta/métodos , Factores de TiempoRESUMEN
The influences of increasing endogenous acetylcholine (eserine) and its blockade (scopolamine) on the effects of sensory stimuli were analyzed through the extracellular recording of the activity of individual hippocampal neurons of awake rabbits. An increase in the level of acetylcholine, accompanied by the appearance of stable theta rhythm, leads to a substantial decrease in the reactivity of neurons, the suppression, attenuation, and inversion of the majority of inhibitory reactions and of a substantial proportion of activational reactions including on-responses of a specific type. At the same time, a limited group of activational reactions is intensified and extended against the background of eserine. Scopolamine, which blocks theta rhythm, does not change or intensifies inhibitory and some activational reactions, including on-responses. Tonic reactions are shortened; however, their gradual extinction disappears. The effects described are preserved in the hippocampus in the presence of basal undercutting of the septum which eliminates ascending brainstem pathways. These data make it possible to draw the conclusion that, under normal conditions, a new (significant) sensory stimulus elicits in the hippocampus an initial stoppage (reset) of activity with the coordinated triggering of theta rhythm and the passage against this background of signals along the cortical input in a specific phase relationship to it. The period of theta modulation switched on by the signal fosters its recording and the limitation of the passage of subsequent, interfering signals. The septohippocampal influences may thus support the mechanism of selective attention, as a necessary precondition for memory.
Asunto(s)
Colinérgicos/farmacología , Hipocampo/citología , Hipocampo/efectos de los fármacos , Neuronas Aferentes/efectos de los fármacos , Estimulación Acústica , Animales , Parasimpatolíticos/farmacología , Parasimpaticomiméticos/farmacología , Fisostigmina/farmacología , Conejos , Escopolamina/farmacología , Ritmo Teta/efectos de los fármacosRESUMEN
The cholinergic modulation of responses of individual neurons and of the focal potentials of the hippocampus, induced by electrical stimulation of the perforant path or mossy fibers were studied in two groups of unanesthetized rabbits, one with an intact septal region (IS), and one with its basal undercutting (BU). In all of the animals the responses to stimulation were blocked or markedly suppressed in a substantial portion of the neurons (50% in IS, 69% in BU) against the background of the administration of eserine. Facilitation of the responses was observed in 10 and 8% of cases, respectively. Scopolamine restored the initial reactivity of hippocampal neurons and intensified responses to stimulation of the perforant path. The effect of eserine was reproduced by stimulation of the medial septal region (MS-DB). The depressive effect of stimulation of the MS-DB was intensified by the administration of eserine and blocked by scopolamine. Brief conditioning stimulation of the MS-DB which imitates a theta salvo facilitated responses to test stimulation of the MS-DB with delays of 70-150 msec, but suppressed them at smaller and greater intervals. Focal potentials in response to stimulation of the perforant path in CA1 were suppressed to an equal extent (by 43%) during sensory stimulation inducing natural theta rhythm, during the action of eserine, and with stimulation of the MS-DB In the BU group, these effects led to the complete suppression of focal potentials; scopolamine restored them. It is hypothesized that the principal function of the septohippocampal cholinergic input resided in the negative filtration of signals arriving against the background of theta rhythm that has been turned on by another, preceding influence, as a result of which their interference with the processing and recording of received information is prevented.
Asunto(s)
Corteza Cerebral/efectos de los fármacos , Colinérgicos/farmacología , Hipocampo/efectos de los fármacos , Neuronas/efectos de los fármacos , Animales , Atención/efectos de los fármacos , Corteza Cerebral/citología , Estimulación Eléctrica , Hipocampo/citología , Potenciales de la Membrana/efectos de los fármacos , Memoria/efectos de los fármacos , Vías Nerviosas/citología , Vías Nerviosas/efectos de los fármacos , Parasimpatolíticos/farmacología , Parasimpaticomiméticos/farmacología , Fisostigmina/farmacología , Conejos , Escopolamina/farmacologíaRESUMEN
The effects of electrical stimulation of the medial septal area (MS-DB) for the purpose of distinguishing and assessing the cholinergic component of the septohippocampal input were investigated in awake rabbits in chronic experiments. Initial inhibitory effects of a standard duration of 40-140 msec (54%) predominated in the intact rabbits. In animals with chronic basal undercutting of the MS-DB, initial inhibitory reactions predominated absolutely (90%). An increase in the level of endogenous acetylcholine by administration of eserine led to a partial or complete suppression of all effects of stimulation in 78% of the hippocampal neurons of the intact rabbits against the background of intensification of the theta modulation of the activity of hippocampal neurons. Scopolamine removed theta modulation and restored the reactivity of neurons to stimulation of the MS-DB. These influences of cholinergic substances were maintained in the animals with basal undercutting of the MS-DB. It is inferred that the general initial influence of septal input on neurons of the hippocampus is expressed in the suppression of their activity ("reset"), which depends on the noncholinergic (GABAergic) component of the septohippocampal connections. The cholinergic component limits the effectiveness of both extraseptal (brainstem) and primary inhibitory septal influences on hippocampal neurons.
Asunto(s)
Encéfalo/fisiología , Colinérgicos/farmacología , Hipocampo/fisiología , Neuronas/fisiología , Sistema Nervioso Parasimpático/fisiología , Acetilcolina/metabolismo , Vías Aferentes/citología , Vías Aferentes/efectos de los fármacos , Vías Aferentes/fisiología , Animales , Encéfalo/citología , Estimulación Eléctrica , Hipocampo/citología , Hipocampo/metabolismo , Terminaciones Nerviosas/efectos de los fármacos , Terminaciones Nerviosas/metabolismo , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Sistema Nervioso Parasimpático/efectos de los fármacos , Sistema Nervioso Parasimpático/metabolismo , Parasimpatolíticos/farmacología , Parasimpaticomiméticos/farmacología , Fisostigmina/farmacología , Conejos , Escopolamina/farmacología , Ritmo TetaRESUMEN
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)
Asunto(s)
Hipocampo/fisiología , Neuronas/fisiología , Ritmo Teta , Animales , HumanosRESUMEN
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.