RESUMEN
Inter-neuronal interactions within the medial septum/diagonal band complex (MSDB) are of great interest as this region is believed to be the hippocampal theta rhythm pacemaker. However, the role of glutamatergic system in functioning of the septal cells is yet unclear. Here, we demonstrate for the first time the effects of glutamate in physiological concentration (1 microM) on the MSDB neuronal spontaneous and evoked activities in vitro. These effects (activation of 70% and inhibition of 30% of responsive neurons) differed in pacemaker and non-pacemaker cells. Pacemaker cells were always activated under glutamate, whereas non-pacemaker neurons could be either activated or inhibited. Indeed, in the burst pacemakers, glutamate increased the frequency of rhythmic activity. In a total MSDB neuron population, in 30% of neurons glutamate applications modified responses to the electrical stimulation by unifying the temporal parameters of neuron responses. Along with the increase in the theta-burst frequency, this indicates that the glutamatergic system is involved in the process ofintraseptal synchronization. Obtained data shed light on the role ofglutamatergic system in septal neuron interactions and broaden our understanding of theta oscillation mechanisms in the septo-hippocampal system.
Asunto(s)
Encéfalo/fisiología , Banda Diagonal de Broca , Potenciales Evocados/efectos de los fármacos , Ácido Glutámico/farmacología , Neuronas/efectos de los fármacos , Ritmo Teta/efectos de los fármacos , Animales , Banda Diagonal de Broca/citología , Banda Diagonal de Broca/efectos de los fármacos , Banda Diagonal de Broca/fisiología , Estimulación Eléctrica , Hipocampo/fisiología , Sciuridae , Ritmo Teta/fisiologíaRESUMEN
EEG traces were recorded from the hippocampus and medial septal area of conscious guinea pigs in control conditions and on repeated stimulation of the perforant path. Changes in the correlations of activity in these structures during stimulation-evoked convulsions (a model of acute epilepsy) and during the process of epileptogenesis (a model of chronic epilepsy) were analyzed. A high correlation between baseline activity in the hippocampus and medial septal area seen in control conditions decreased sharply with the appearance of acute and chronic convulsions. Kindling led to hippocampus-independent generation of field convulsive discharges in the medial septal area. During kindling, there was a gradual disintegration of activity in the hippocampus and septum, which provides evidence for impairment of the operation of the septo-hippocampal network during epileptogenesis.
Asunto(s)
Epilepsia/fisiopatología , Cobayas/fisiología , Hipocampo/fisiopatología , Excitación Neurológica/fisiología , Tabique del Cerebro/fisiopatología , Animales , Electroencefalografía/métodos , Vía Perforante/fisiopatología , Convulsiones/fisiopatologíaRESUMEN
Comparative studies of the activity of extracellularly recorded neurons in living slices of the medial septal area of healthy guinea pigs and animals with a model of chronic temporal epilepsy demonstrated differences between them in terms of the frequency and pattern of cell discharges. The brains of animals with experimental epilepsy showed a doubling of the total level of activity as compared with controls, due to increases in the discharge frequencies of irregular and regular non-volleying neurons. There was a sharp (three-fold) increase in the number of cells with rhythmic discharge volleys, along with changes in the parameters of volley activity - both in neurons with the endogenous (pacemaker) pattern and in cells with secondary involvement in rhythmic activity. The possible mechanisms for these changes are discussed. These data widen our understanding of the processes forming pathological synchronization in epilepsy and may assist in the creation of new approaches to the treatment of this disease.
Asunto(s)
Neuronas/fisiología , Periodicidad , Tabique del Cerebro/fisiopatología , Potenciales de Acción , Animales , Modelos Animales de Enfermedad , Epilepsia/inducido químicamente , Epilepsia/fisiopatología , Agonistas de Aminoácidos Excitadores/efectos adversos , Cobayas , Ácido Kaínico/efectos adversos , Factores de TiempoRESUMEN
Despite extensive interest in studies of the medial septal area, the nature of the interactions of its various neurochemical systems remains largely unclear. The aim of the present work was to clarify the role of nicotinic receptors in mediating the interaction of the glutamatergic and cholinergic systems in this structure. Extracellular recording of neuron activity in living slices of ground squirrel brain was used to study the influences of L-glutamate (1 microM) during application of the nicotinic receptor blocker hexamethonium (1 mM). The responses of septal neurons to glutamate depended on the type of their initial activity and the presence of pacemaker properties. This study is the first to show that glutamate increases the frequency of volleys in rhythmic neurons in the septum. Hexamethonium induced changes in neuron activity similar to the influences of glutamate. After prior application of hexamethonium, the responses of neurons to glutamate changed: activatory responses were masked and inhibitory responses were enhanced. Cholinergic modulation of the responses of septal neurons to glutamate were shown to occur, as did modulation of the strength of the oscillatory properties of the septal network by nicotinic receptors.
Asunto(s)
Ácido Glutámico/metabolismo , Hexametonio/farmacología , Neuronas/efectos de los fármacos , Antagonistas Nicotínicos/farmacología , Receptores Nicotínicos/metabolismo , Núcleos Septales/efectos de los fármacos , Potenciales de Acción/efectos de los fármacos , Potenciales de Acción/fisiología , Animales , Hibernación , Técnicas In Vitro , Neuronas/metabolismo , Receptores Nicotínicos/efectos de los fármacos , Sciuridae , Núcleos Septales/citología , Núcleos Septales/metabolismoRESUMEN
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.