Intranasal epitalon infusion modulates neuronal activity in the rat neocortex

Properties of tetrapeptide epitalon (Ala-Glu-Asp-Gly) constructed on the basis of pineal peptide extract, have been studied. The intranasal infusions: a noninvasive way to deliver this peptide to CNS hypassing the blood-brain barrier, was used. The aim of the study is to estimate epitalon action on rat motor cortex spontaneous activity. Wistar male rats were anesthetized with urethane (1 g/kg). Extracellular unit recording was made using glass microelectrodes (1-2 MOhm). After recording of spontaneous activity (10-15 min), epitalon intranasal infusion (2 ng) was followed by 30-minute recording. Within a few minutes after the infusion, significant activation of neural activity was observed (2-2.5-fold higher frequency of neuronal spikes). Complex response consisting of several phases was identified in some recordings. The spikes frequency growth during 5 to 7 min (first phase) after the infusion was followed by the second (11-12 min) and the third (17-18 min) phases. An increase of neuronal spontaneous activity was conditioned by the higher frequency of already active units and by the involvement of previously silent cells. At least the first phase of epitalon action can be explained by direct action of the peptide on the cells of the motor cortex.     

Coordination of neuronal activity by gap junctions in the developing neocortex

During embryonic development, gap junctions link cells into functional communication compartments characterized by a common development fate. Increasing evidence for gap junctions between immature neurons suggest that similar mechanisms may also be at work in the developing vertebrate brain, where gap junction-coupled neuronal assemblies often precede synaptically-linked functional networks. Recent experiments in the developing mammalian neocortex demonstrated the presence of gap-junction mediated second messenger waves, similar to those in non-neuronal cells. The primary function of neuronal gap junctions, therefore, might be to coordinate biochemical activity, rather than to act as purely electrical synapses. Thus, gap junctions may serve to amplify neuronal activity produced by weak synaptic stimulation.     

The neuronal activity of suspension grafts of the neocortex]

Were compared electrophysiological characteristics of suspension (SUS) and solid (SOL) tissue grafts of embryonic neocortex transplanted into the barrel field of adult rats. The level of survival of SUS and SOL grafts did not differ significantly (89% and 95% correspondingly). All SUS grafts were integrated with the host brain judging by histological and electrophysiological criteria. Reactivity of neurons to electrical stimulation of the recipient's brain and to sensory (tactile) stimulation, as well as the latencies of on-responses were similar in both types of the grafts. However, proportion of neurons with on-responses was nearly twice lower in SUS grafts, while the number of neurons responding to tactile stimulation by primary suppression of activity was significantly higher than in SOL ones. It is suggested that the derangement of primary architectonics unavoidable during preparation of suspensions is responsible for the described differences between SUS and SOL grafts.     

Mechanisms to synchronize neuronal activity

 Temporal aspects of neuronal activity have received increasing attention in recent years. Oscillatory dynamics and the synchronization of neuronal activity are hypothesized to be of functional relevance to information processing in the brain. Here we review theoretical studies of single neurons at different levels of abstraction, with an emphasis on the implications for properties of networks composed of such units. We then discuss the influence of different types of couplings and choices of parameters to the existence of a stable state of synchronous or oscillatory activity. Finally we relate these theoretical studies to the available experimental data, and suggest future lines of research. Received: 20 July 1999 / Accepted in revised form: 23 August 2000     

Structure of background neuronal activity in thin slices of guinea-pig neocortex

We recorded background neuronal discharges extracellularly in guinea-pig cerebral cortex slices maintainedin vitro. The following types of activity were delineated: 1) regular single discharges (38.5%), 2) irregular spikes (6.5%), 3) bursts (6.5%), 4) burst-and-single discharge (mixed) activity (26.5%), 5) group discharges (2.5%), 6) multicellular volleys (18.5%). Each of these types corresponds to a characteristic distribution of interspike intervals in the form of an autocorrelogram. Regular pacemaker-type discharges, which are never observed in normal or isolated cortex, appeared in small volumes of grey matter and in the absence of afferentation.Institute of Biological Physics, Academy of Sciences of the USSR, Pushchino. Translated from Neirofiziologiya, Vol. 17, No. 4, pp. 441–449, July–August, 1985.     

Effect of piracetam on the neuronal activity of the neocortex and on behavior in rabbits during learning

Against the background of the action of piracetam--a cyclic derivative of GABA--in a dose of 200-400 mg/kg, no significant changes were observed of probabilities of motor reactions to inhibitory and reinforced light flashes. Piracetam in that dose did not affect inhibitory pauses in responses of neurones in the visual area and corresponding late components of the evoked potential to nonreinforced light flashes, i.e. it did not intensify inhibitory hyperpolarization processes in the cerebral cortex. Piracetam administration improved differentiation of inhibitory and reinforced light flashes judging by bioelectric parameters of the brain activity as a result of intensification of pain reinforcement action on cortical neurones. The carried-out experiments revealed significant differences in neurophysiological mechanisms of action of piracetam and fenibut--GABA linear derivate related to nootropic class.     

Low dose isoflurane exerts opposing effects on neuronal network excitability in neocortex and hippocampus

The anesthetic excitement phase occurring during induction of anesthesia with volatile anesthetics is a well-known phenomenon in clinical practice. However, the physiological mechanisms underlying anesthetic-induced excitation are still unclear. Here we provide evidence from in vitro experiments performed on rat brain slices that the general anesthetic isoflurane at a concentration of about 0.1 mM can enhance neuronal network excitability in the hippocampus, while simultaneously reducing it in the neocortex. In contrast, isoflurane tissue concentrations above 0.3 mM expectedly caused a pronounced reduction in both brain regions. Neuronal network excitability was assessed by combining simultaneous multisite stimulation via a multielectrode array with recording intrinsic optical signals as a measure of neuronal population activity.     

Effects of ketamine on neuronal epileptiform responses in the cat neocortex

The effects of ketamine, an antagonist of NMDA receptors, on the neuronal epileptiform responses evoked by applications of strychnine, penicillin, or bicuculline to the suprasylvian gyrus were studied in cats. Ketamine either exerted no effect, or slightly decreased interictal high-amplitude depolarizing shifts of the membrane potential and depolarizing afterpotentials, which appeared spontaneously or were evoked by intracortical stimulation. Repetitive electrical stimulation of the epileptogenic cortical regions resulted in the appearance of autogenerated ictal activity lasting up to several tens of seconds; this activity was produced against the background of a depolarization of neuronal membranes. After ketamine injections, such stimulations evoked no ictal activity in the neurons, or the discharges became much shorter. The results of our study show that the NMDA-dependent postsynaptic components play a more important role in the development of neocortical ictal activity compared with the interictal activity.Neirofiziologiya/Neurophysiology, Vol. 27, No. 1, pp. 32–35, January–February, 1995.     

Conjugation of the neuronal impulse activity in the rabbit neocortex during self stimulation of the lateral hypothalamus

Correlation of impulse activity of visual and sensorimotor neurons of both hemispheres in 10-s interval after self-stimulation of the right and left lateral hypothalamus was studied by plotting cross- and autocorrelation histograms. The number of cell pairs, in which sensorimotor neurons discharged after visual ones, increased after self-stimulation (from 24 +/- 6 to 44 +/- 7%). Frequencies of the alpha- and theta-range in crosscorrelograms increased; the alpha frequency increased mainly in the right hemisphere, while the theta frequency increased in the left hemisphere. The interhemispheric asymmetry in the interaction between cortical neurons was not associated with the side of hypothalamic stimulation.     

Cyclin-dependent kinase 5 and neuronal migration in the neocortex

The cyclin-dependent kinase 5 (Cdk5) plays an important role in the proper establishment of neocortical layers. Over the past several years, key molecular targets of Cdk5 have been identified that show intriguing connections to the adhesional and cytoskeletal components of cell movement. This molecular knowledge about Cdk5 signaling has begun to translate into an understanding of how Cdk5 regulates the cellular physiology of neocortical layer formation. Together with recent progress on the signaling relationship between Cdk5 and Reelin, the other key protein involved in neocortical layer formation, and their relationship to migration modes, research on understanding neocortical layer formation has arrived at a most promising crossroad.     

Postsynaptic components of paroxysmal neuronal response in the strychninized neocortex

Neuronal response in the strychninized cortical suprasylvian gyrus was investigated in experiments on immobilized and unanesthetized cats using intracellular techniques. Paroxysmal depolarizing shifts (PDS) in neuronal membrane potential were recorded, consisting of a bursting discharge and slow depolarization wave. It was found when using intracortical stimulation that PDS can accumulate and change in shape and size. Bursting discharges in PDS were induced by large-scale EPSP which could be distinguished from paroxysmal response. Data from presumably intradendritic readings demonstrated the presence of large-scale EPSP during the generation of epileptiform discharges in the cortex. In a proportion of cells, PDS were accompanied by hyperpolarizing potentials — apparently IPSP, since they undergo reversal with intercellular administration of Cl^–. The contribution of excitatory and inhibitory synaptic influences to paroxysmal neuronal response is discussed.I. I. Mechnikov State University, Odessa. Translated from Neirofiologiya, Vol. 22, No. 5, pp. 642–649, September–October, 1990.     

Mechanisms of establishing long-term fluctuations in the activity of neuronal networks. I. Stochastic uniform neuronal networks

The possibility of generating long-term self-terminating activity lasting some hundreds of milliseconds in neuronal networks with positive (excitatory) feedback was investigated using a computerized mathematical simulation model. This auto-termination is compounded of several factors: stochasticity of the neuronal network, mediating fluctuations in activity level; neuronal interaction, leading either to synchronized discharges and hence of postactivational inhibitory processes, or else to a reorganization of the microstructure underlying neuronal network activity mainly conducive to excitation of neurons with tenuous connections. The likely contribution of these mechanisms to establishing long-term self-terminating activity in the cerebral neuronal networks responsible for different types of programmed rhythmic activity (or generators) is discussed.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 18, No. 3, pp. 382–391, May–June, 1986.     

Anesthetic and postanesthetic effects of isoflurane on neuronal activity in the rat hippocampus

In this study, we explored anesthetic and postanesthetic effects of isoflurane on GABA-ergic and glutamatergic systems in the rat hippocampus. Our results demonstrate that different neuronal targets affected by isoflurane recover from anesthesia at dissimilar rates. Neirofiziologiya/Neurophysiology, Vol. 39, Nos. 4/5, pp. 371–373, July–October, 2007.     

Corticofugal effects on the neuronal activity in the emotiogenic/motivational zones of the hypothalamus

Neuronal responses to stimulation of the proreal (field 8) and cingular (field 24) cortices, pyriform lobe (periamygdalar cortex), and hippocampus (CA3) were studied in the lateral (HL) and ventromedial (Hvm) hypothalamus, dorsal hypothalamic region (aHd), and projection region of the medial forelimb bundle (MFB); single and repeated (series of a 6–300 sec⁻¹ frequency) stimuli were used. At single stimulations, the minimum proportion of inhibitory responses with respect to excitatory effects was observed when the neocortex (the proreal gyrus) was stimulated; this proportion became successively greater at stimulations of the intermediate cortex (the cingular gyrus) and paleocortex (the pyriform cortex), while stimulation of the archicortex (the hippocampus) evoked mostly inhibitory responses. At repeated stimulation of the cortical structures, inhibitory responses prevailed in the neurons under study: their total number was nearly four times larger than that of excitatory reactions. The response patterns to single and serial stimulations of the cortical structures allowed us to demonstrate: (i) significant diversity of the influences received by hypothalamic neurons from the cortical structures and (ii) the dependence of the pattern of these influences on the phylogenetic specificity of the above structures.     

Time-dependent changes in ghrelin-immunoreactivity in dissociated neuronal cultures of the newborn rat neocortex

Ghrelin is a hormone, initially described as a gastric peptide stimulating appetite and growth hormone secretion, which also has an important role in the regulation of many other processes, including higher brain functions. Ghrelin has been described in situ in different parts of the brain, but so far there has been no data about its expression in cell cultures. Therefore, we aimed in this study to investigate the levels of ghrelin in dissociated cortical neurons at various times in culture. We applied the ABC immunocytochemical method for the detection of ghrelin in one-day-, one-week-, and two-week-old cultures. Our results clearly show that at the early stages after plating the cultures 86.2% (± 8.93) of the neurons are ghrelin-positive and their number decreases during the culturing period. As ghrelin is present in the majority of cultured newborn neurons, when the neuronal differentiation and network formation take place, it may also influence the early synaptic formation and cell-to-cell interactions, which are both very important for network functions like learning and memory.