Role of the frontal lobes in integrative activity of the brain inMacaca mulatta

Unit activity in the frontal cortex (s. principalis) during the performance of a complex behavior program -nonspecific expectation after a warning stimulus, conditioned stimulus, and delay period, trigger signal, and alternative choice, followed by food award -was studied by the multineuronal recording method. Processes of combination of external stimuli into an integrated program, retention of stimulus traces in the memory, and correct and incorrect problem solving were reflected in the unit activity of s. principalis. The level of the correct responses of choice and the corresponding correlates in modifications of unit activity depended directly on the level of food motiviation. The results are discussed from the standpoint of the evolutionary formation of the thalamo-frontal association system of the brain, connected with the formation of behavior programs in accordance with current biological motiviation.Translated from Zhurnal Évolyutsionnoi Biokhimii i Fiziologii, Vol. 14, No. 2, pp. 144–150, March–April, 1978.     

Picrotoxin-induced epileptiform activity in hippocampus: role of endogenous versus synaptic factors

Picrotoxin-(PTX) induced epileptiform activity was studied in guinea pig hippocampal slices maintained in vitro, using intra- and extracellular recording techniques. The observed pattern of spontaneous and evoked epileptiform activity was quite complex. Spontaneous epileptiform events originated in the CA3 region and subsequently spread or propagated to CA1. Activation of CA1 could then reactivate CA3. This reverberation of activity was seen also following stimulation of the mossy fiber afferents from the dentate gyrus to CA3. Stimulation of fibers in the stratum radiatum of the CA1 region could trigger, at short latency, epileptiform activity that either was localized in CA1 or also occurred in CA3, with a late secondary discharge in CA1. This is attributed to a backfiring of the Schaffer collaterals and illustrates the ability of a variety of CA3 inputs to trigger epileptiform activity. Bath-applied PTX, at concentrations of 50-200 microM, had no apparent effect on the resting membrane potential or input resistance of the CA3 cells tested. Depolarizing current pulses elicited characteristic endogenous-burst responses that were not altered by PTX. Synaptic activity evoked by mossy fiber stimulation was altered markedly by PTX. The pattern of observed changes indicated that PTX reduced inhibitory postsynaptic potential (IPSP) amplitudes, resulting in the appearance of repetitive (presumably recurrent) excitatory inputs. Paroxysmal depolarizing shifts ( PDSs ) were generated by the coalescence of these excitatory inputs. Two types of spontaneous bursting were observed after PTX application. The first type was nonepileptiform , all or none in nature, and its frequency was voltage dependent. The second type of spontaneous burst was the PDS. It was epileptiform in character because it was associated with the synchronous discharge of many neurons. It was graded in nature, and its frequency was voltage independent. The graded nature of the PDS was demonstrated by varying the duration and intensity of the orthodromic stimulation. Trains of stimulation could produce PDSs that lasted 500-800 ms. A refractory period was observed following a PDS. By varying the strength of the orthodromic stimulation, it was possible to demonstrate that for the intervals tested this was a relative, not absolute, refractory period. Intracellular recordings in CA3 neurons indicated that each spontaneous PDS was followed by an afterhyperpolarization (AHP).     

Disturbances in the integrative activity of the rat brain after bilateral focal compression ischemia of the frontal cortex

Pathomorphological changes and disturbances in the integrative activity of the central nervous system of rats are studied after bilateral compression ischemia of the frontal cortex. Bilateral compression of the frontal cortex is shown to result in the formation of limited foci of ischemic necroses in the cortex, which are surrounded by the perifocal zone. This is attended by reduced horizontal motor activity in the “open field” test, as well as by a reduced latency of the conditioned passive avoidance response. The motor activity of operated animals is restored on day 14 postoperation, correlating with regeneration of some damaged neurons in the perifocal zone, whereas the latency of the conditioned passive avoidance response remains markedly reduced. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 118, N ^o 12, pp. 568–571, December, 1994 Presented by O. S. Adrianov, Member of the Russian Academy of Medical Sciences     

Effect of potentiated antibodies to brain-specific protein S100 on the integrative activity of the brain

Effect of potentiated antiserum to brain-specific protein S100 in a concentration of 10⁻¹⁰⁰ prepared according to standard homeopathic procedures on integrative activity of rat brain was studied on models of conditioned avoidance reaction and self-stimulation of the lateral hypothalamus through chronically implanted electrodes. The antibodies reversibly inhibit memory processes during avoidance reaction. The incidence of the self-stimulation reaction increased after single administration of potentiated antibodies, while their administration for 5 days decreased the incidence of this reaction. Administration of water caused no such effects. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 5, pp. 547–549, May, 1999     

The role of sympathetic efferent activity in the regulation of brain temperature

The role of nasal heat exchange in the control of brain temperature has been studied in cats, pigs, ducks and rabbits during acute experiments under general anaesthesia. Nasal air flow at physiological rates caused hypothalamic temperature to fall at beween 0.2 and 0.5°C/min in cats, pigs and ducks, which all have arterial rete systems that can cool blood flowing to the brain, but not in rabbits, which lack an arterial rete. Bilateral stimulation of cervical sympathetic trunks reduced or abolished the brain cooling effect of nasal air flow in cats, pigs and ducks. After a period of airflow during which brain cooling was reduced by sympathetic stimulation, the end of stimulation was sometimes followed by marked and rapid brain cooling, indicating re-perfusion through ischaemic cooled tissues. Cervical sympathetic stimulation caused a reduction in resistance to nasal airflow in all species studied, by inducing vasoconstriction and shrinkage of the nasal mucosa. In species with well-developed arterial retia, the effect of cervical sympathetic stimulation in regulating nasal cooling of the brain is probably mediated by controlling blood flow through the nasal mucosa. Although this vascular control also occurs in rabbits, they cannot selectively cool the brain and sympathetic stimulation has no effect on rabbit brain temperature.     

The role of the pontis oralis in the generation of RSA activity in the hippocampus of the guinea pig

The relationship between field activity in the nucleus pontis oralis (PnO) and the hippocampus was examined in the guinea pig. Rhythmical slow activity (RSA or theta activity) could be recorded from both the pontis oralis and the hippocampus. RSA recorded in the pontis oralis was of the same principal frequency as that found in the hippocampus, but had a much lower amplitude. Behavioral correlates of PnO RSA were the same as the behavioral correlates of hippocampal RSA. The effects of atropine sulfate on RSA were the same at each site. Stimulation of the PnO produced RSA in the hippocampus. Lesions of the PnO had no effect on RSA recorded from the hippocampus or on the behavioral correlates of this RSA. Lesions of the medial septum abolished RSA in both sites. Cross-correlations between field activity recorded from both the hippocampus and PnO showed the same time lag before and after septal lesions. These results indicate that while the PnO is not instrumental in the production of hippocampal RSA, an intact septum is necessary for the production of RSA in both sites. They also indicate that there is a common projection to these sites which does not pass through the medial septum.     

Consciousness as the highest integrative function of brain]

This study has attempted to show that consciousness (sense) can develop only in the living systems during natural evolution based on self-organization. While modelling the systems experimentally, it is impossible to reproduce consciousness phenomena. This fact points to the global differences in the principles of management of living systems as compared to the artificial ones. Due to the existence of various forms of consciousness (from the simplest forms, such as sensing, perception, and feeling to the most complicated ones, such as motivation and desire), the living organisms are capable to interpret the complex neurodynamics of the brain into a simple and functionally significant integral form for them. Owing to consciousness, the behavior of living systems at the highest level of evolution (a human being) becomes an indeterminate behavior with the clearly expressed position of will freedom; it is also important that through consciousness an individual can influence different physiological mechanisms of living organisms.     

Propagation velocity of epileptiform activity in the hippocampus

Summary The propagation of epileptiform burst activity was investigated in the CA1 area of the in-vitro hippocampal slice preparation of the guinea pig. This activity was provoked by 0.1 mM 4-aminopyridine in the bathing medium and was recorded in the pyramidal layer with an array of eight electrodes. The delay between the first population spike of a burst recorded with different electrodes was calculated using the cross-correlation function. The propagation velocity was estimated from the delays and the electrode intervals. It was found that the velocity of spontaneous and evoked epileptiform bursts varies between 0.15 and 5 m/s and is not confined to the range of conduction velocities of the fibre systems in CA1 (0.3–0.55 and 1.0–1.8 m/s). Different velocities can be present in different parts of the CA1 area and the initiation of spontaneous bursts is not confined to the CA2–3 areas, but can also occur in CA1. Burst activity also propagated in a low calcium-high magnesium medium. Different mechanisms of propagation are discussed and it is argued that the propagation velocity due to ephaptic interaction may vary largely. It is concluded that epileptiform activity can be propagated not only by synaptic connections at or near the pyramidal layer, but also by way of electrical field effects of population spikes.     

Ischemia-induced changes in the electrical activity of the hippocampus

Summary Consequences of transient (15–20 min) ischemia on the neuronal activity of the dentate gyrus and hippocampal CA 1 region were investigated in chronically implanted Sprague-Dawley rats. Forebrain ischemia was produced by occlusion of the carotids for 15 or 20 min, following cauterization of the vertebral arteries. Following the release of the carotids, both spontaneous and evoked activity showed a steady but partial recovery, reaching a maximum 12 to 24 h after the ischemic insult. From this plateau, both the power of rhythmic slow activity recorded during walking and the power of slow delta activity obtained during alert immobility decreased monotonically, with large changes occuring between postischemic days 2 and 4. The changes in spontaneous activity were accompanied by a decrease and eventual disappearance of the Schaffer collateral evoked responses in CA 1. Perforant path volleys were less efficient in activating the granule cells following ischemia compared to baseline levels. This decreased responsiveness was paralleled by a relative impairment of paired pulse depression. Neurophysiological signs of spontaneous or evoked neuronal hyperexcitability were not observed at any time point during the 8 postischemic days. Neuronal damage in the CA 1 region varied from moderate to complete loss of pyramidal cells. In addition, degenerating neurons were also observed in the hilus of the dentate gyrus. These findings do not support the overwork version of the excitoxic hypothesis of delayed neuronal damage and indicate that the cause of ischemic cell death should be sought in factors other than neuronal hyperactivity.     

Low-calcium epileptiform activity in the hippocampus in vivo

It has been clearly established that nonsynaptic interactions are sufficient for generating epileptiform activity in brain slices. However, it is not known whether this type of epilepsy model can be generated in vivo. In this paper we investigate low-calcium nonsynaptic epileptiform activity in an intact hippocampus. The calcium chelator EGTA was used to lower [Ca2+]o in the hippocampus of urethane anesthetized rats. Spontaneous and evoked field potentials in CA1 pyramidal stratum and in CA1 stratum radiatum were recorded using four-channel silicon recording probes. Three different types of epileptic activity were observed while synaptic transmission was gradually blocked by a decline in hippocampal [Ca2+]o. A short latency burst, named early-burst, occurred during the early period of EGTA application. Periodic slow-waves and a long latency high-frequency burst, named late-burst, were seen after synaptic transmission was mostly blocked. Therefore these activities appear to be associated with nonsynaptic mechanisms. Moreover, the slow-waves were similar in appearance to the depolarization potential shifts in vitro with low calcium. In addition, excitatory postsynaptic amino acid antagonists could not eliminate the development of slow-waves and late-bursts. The slow-waves and late-bursts were morphologically similar to electrographic seizure activity seen in patients with temporal lobe epilepsy. These results clearly show that epileptic activity can be generated in vivo in the absence of synaptic transmission. This type of low-calcium nonsynaptic epilepsy model in an intact hippocampus could play an important role in revealing additional mechanisms of epilepsy disorders and in developing novel anti-convulsant drugs.     

Melatonin modulates cytoskeletal organization in the rat brain hippocampus

Melatonin concentration in plasma reaches high levels during the night and synchronizes body rhythms with the photoperiod. Previous evidence obtained in cultured cells suggests that melatonin synchronizes cytoskeletal re-arrangements at nocturnal plasma concentration. In this study, we determined the amount of microtubules and microfilaments in the rat hippocampus as an index of cytoskeletal organization in rats submitted to a photoperiodic regime. Additionally, these parameters were determined in control rats, sham rats, pinealectomized rats, and rats that were pinealectomized and treated with melatonin for 1 week. The results showed an increase in both the amount of microfilaments in the hippocampus of rats sacrificed in the dark phase, and in melatonin levels. In addition, a decrease in both microfilament and microtubule amounts occurred in pinealectomized rats. In contrast, melatonin treatment partially reestablished actin and tubulin proportions organized in microfilaments and microtubules, respectively. The results indicate that actin organization in microfilaments was associated with both the photoperiod and with melatonin levels. Together, the data support that cytoskeletal organization is regulated rhythmically by melatonin in synchrony with the photoperiod.     

Neurobiology of the integrative activity of the brain: Some properties of long-term posttetanic heterosynaptic depression in the motor cortex of the cat

It has been demonstrated that long-term posttetanic heterosynaptic depression (LTHD), manifested in the form of a prolonged decrease in the probability of monosynaptic responses of the cell to stimulation of that afferent pathway which was not activated during conditioning tetanization of another input, takes place in the neocortex, as it does in the hippocampus. LTHD is characterized by such properties as its long-term character, cooperativity, and nonspecificity of input. LTHD in the nonconditioned input and long-term posttetanic potentiation or long-term posttetanic homosynaptic depression in the conditioned input may develop both in parallel or independantly of one another. It is hypothesized on the basis of the results obtained that LTHD (as is the case with LTP and LTD) is a calcium-dependant phenomenon, and that the achievement of a specific level of depolarization of the membrane in the region of the disposition of the inactive synapses is required for its occurrence. “Contrasting,” i.e., a relative increase in the efficiency of transmission in the activating synapse, may be effected through LTHD; LTHD may be one of the mechanisms underlying forgetting. Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti imeni I. P. Pavlova, Vol. 43, No. 6, pp. 1177–1185, November–December, 1993.     

Epileptiform activity in the hippocampus produced by tetraethylammonium

1. The epileptiform discharges in the CA3 region of the rat hippocampal slice produced by bath application of the potassium channel blocker tetraethylammonium (TEA) were investigated. The effects of a convulsant (5 mM) and subconvulsant (0.5 mM) concentration of TEA on the mossy fiber-evoked synaptic currents were studied by the use of voltage-clamp techniques to determine whether TEA, like 4-aminopyridine (4-AP), another potassium channel blocker and convulsant, increased both inhibitory and excitatory components of the synaptic response. 2. At extracellular potassium concentrations of 2.5 mM, TEA (5 mM) was found to produce spontaneously occurring epileptiform discharges that could be recorded extracellularly. The intracellular correlate of the epileptiform discharge, the paroxysmal depolarizing shift (PDS), could be reversed in polarity by depolarizing the membrane and was associated with a large increase in membrane conductance. These results suggest that a synaptically mediated potential underlies the generation of the epileptiform discharge. 3. The reversal potential for the PDS was dependent on the time, relative to the extracellularly recorded field discharge, at which the measurement was made. In current clamp the mean reversal potential of the PDS measured at the midpoint of the extracellular discharge was -3.3 +/- 2.9 (SE) mV (n = 9). The reversal potential of the PDS was considerably more negative when measured either before or after the midpoint of the extracellular discharge, suggesting the presence of an inhibitory synaptic component. In voltage clamp similar results were obtained and a large conductance change was found to be associated with the PDS. These results suggest that the synaptic conductance associated with the PDS has both inhibitory and excitatory components. 4. TEA increased significantly the mossy fiber-evoked, early-inhibitory conductance. A convulsant concentration (5 mM) increased the conductance measured 15 ms after the stimulus from 39.7 +/- 8.7 to 87.2 +/- 8.0 nS (n = 6). The reversal potential associated with the conductance depolarized from -68.3 +/- 3.4 to -58.3 +/- 4.0 mV after 5 mM TEA. A subconvulsant concentration of TEA (0.5 mM) also increased the conductance of the mossy fiber-evoked response at 15 ms after the stimulus from 49.5 +/- 3.1 to 63.1 +/- 6.1 nS (n = 4) without an associated shift in reversal potential. 5. The late-inhibitory component of the mossy fiber-evoked response, when present, was increased by 5 mM TEA and unchanged by 0.5 mM TEA. 6. The excitatory mossy fiber-evoked synaptic current was studied in the presence of picrotoxin and was found to be increased and prolonged by 5 mM TEA.(ABSTRACT TRUNCATED AT 400 WORDS)