Impulse Activity Of Neurons Research Articles

The Effect of Triterpene Glycosides on Electrical Activity Changes of Identified Mollusk Neurons

The effect of mono- and bisdesmoside triterpene glycosides on the background activity of the grape snail Helix pomatia identified neurons was studied. Monodesmoside glycosides at concentrations of 10-3-10-4 M elicit stable hyperpolarization of neurons by increasing the membrane permeability for K+ ions. At concentrations of 10-5-10-7 M, they briefly change the neuronal impulse activity. The type of monodesmoside triterpene glycoside activity on neurons depends on the structure of the hydrocarbon. The glycoside effect on neuron membranes is related to the hemolytic activity

Enhanced Vulnerability to Cocaine Self-Administration Is Associated with Elevated Impulse Activity of Midbrain Dopamine Neurons

Individual differences in responding to a novel environment predict behavioral and neurochemical responses to psychostimulant drugs. Rats with a high locomotor response to a novel environment (HRs) exhibit enhanced self-administration (SA) behavior, sensitization, and basal or drug-induced dopamine release in the nucleus accumbens compared with rats with a low response to the novel context (LRs). In this study, we determined whether such differences in vulnerability to drug addiction might be related to differences in dopamine (DA) neuron activity. Rats were divided into HRs and LRs according to their response to a novel environment and then tested for acquisition of cocaine SA. HRs rapidly acquired cocaine SA (175 microg/kg per infusion), whereas LRs did not. Differences in cocaine SA were not caused by differences in exploratory behavior or sampling because these behaviors did not differ in HRs and LRs self-administering a saline solution. In a separate experiment, we used extracellular single-unit recordings and found that HRs exhibit higher basal firing rates and bursting activity of DA neurons in the ventral tegmental area and, to a lesser extent, in the substantia nigra pars compacta. The greater activity of midbrain DA cells in HRs was accompanied by reduced sensitivity to the inhibitory effects of a DA D2-class receptor agonist, indicating possible subsensitivity of impulse-regulating DA autoreceptors. These results demonstrate that differences in the basal activity of DA neurons may be critically involved in determining individual vulnerability to drugs of abuse.

Background neuronal activity in thenucleus supraopticus and its modifications under the influence of parathyroid hormone

In experiments on anesthetized cats, we found that i. v. injection of 5.0 U/kg of parathyroid hormone (PTH) results in modifications of the statistical parameters of the neuronal impulse activity in thenucleus supraopticus (SO) of the hypothalamus. Sliding frequency graphs, histograms of interspike intervals, autocorrelograms, and serial correlation coefficients were plotted and calculated before and after PTH injections; their comparison demonstrates that the hormone significantly modulates the temporal organization of spike trains generated by the neurons of this nucleus. We observed that PTH mostly activated SO neurons and diminished the level of spike grouping in their activity. The effect of PTH to a certain level depended on the initial frequency of background activity: an increase in the spiking frequency was typical of primarily dominating “low-frequency” neurons, while “high-frequency” units were mostly inhibited. The possible mechanisms of the observed modifications are discussed.

Striatal Neuronal Activity and Responsiveness to Dopamine and Glutamate after Selective Blockade of D1 and D2 Dopamine Receptors in Freely Moving Rats

Although striatal neurons receive continuous dopamine (DA) input, little information is available on the role of such input in regulating normal striatal functions. To clarify this issue, we assessed how systemic administration of selective D1 and D2 receptor blockers or their combination alters striatal neuronal processing in freely moving rats. Single-unit recording was combined with iontophoresis to monitor basal impulse activity of dorsal and ventral striatal neurons and their responses to glutamate (GLU), a major source of excitatory striatal drive, and DA. SCH-23390 (0.2 mg/kg), a D1 antagonist, strongly elevated basal activity and attenuated neuronal responses to DA compared with control conditions, but GLU-induced excitations were enhanced relative to control as indicated by a reduction in response threshold, an increase in response magnitude, and a more frequent appearance of apparent depolarization inactivation. In contrast, the D2 antagonist eticlopride (0.2 mg/kg) had a weak depressing effect on basal activity and was completely ineffective in blocking the neuronal response to DA. Although eticlopride reduced the magnitude of the GLU response, the response threshold was lower, and depolarization inactivation occurred more often relative to control. The combined administration of these drugs resembled the effects of SCH-23390, but whereas the change in basal activity and the GLU response was weaker, the DA blocking effect was stronger than SCH-23390 alone. Our data support evidence for DA as a modulator of striatal function and suggest that under behaviorally relevant conditions tonically released DA acts mainly via D1 receptors to provide a continuous inhibiting or restraining effect on both basal activity and responsiveness of striatal neurons to GLU-mediated excitatory input.

Selection of actions in the basal ganglia–thalamocortical circuits: review and model

The paper reviews the 20-year experience of recording impulse activity of neurons in the basal ganglia–thalamocortical circuits. These recordings were made from patients with Parkinson's disease who failed to respond to conventional medical treatment and who had undergone stereotaxic neurosurgery. When taken together, the results show that: (1) the basal ganglia–thalamocortical circuits become active only when a stimulus is attended or when a movement is voluntarily implemented, i.e. they are involved in the process of selection of an appropriate sensory stimulus for advanced processing and in the process of selection of an appropriate motor action for achieving a certain goal; (2) neuronal circuits responsible for assessment actions and for motor acts are segregated; (3) inhibitory opponent neuronal mechanisms are implemented for initiating and suppressing inappropriate actions; and (4) preparation to make different assessment actions (attentional set) is associated with different preparatory activities. To explain these findings a hypothesis of action programming has been formulated. According to it, the whole of human behavior is divided into separate sensory–motor–cognitive actions, while the brain in turn is divided into separate systems playing different roles in the organization of actions. The system for action selection that includes the basal ganglia–thalamic circuits plays a critical role in initiation of, preparation for, and suppression of these actions. The neuronal mechanisms for the system for action selection including mapping of actions, `winner takes all' operations in the striatum, disinhibition and inhibition processes in the thalamus are suggested and discussed.

Differential actions of dizocilpine (MK-801) on the mesolimbic and mesocortical dopamine systems: role of neuronal activity

The significance of impulse activity in the dopamine neurons of the ventral tegmental area for the dopamine release evoked by systemic administration of the psychotomimetic drug dizocilpine (MK-801) was investigated. Dual probe microdialysis was utilized in freely moving rats implanted with one probe in the ventral tegmental area and a second ipsilateral probe in either the nucleus accumbens or the medial prefrontal cortex. Dialysates were analyzed with high-performance liquid chromatography with electrochemical detection for dopamine. The ventral tegmental area was perfused with the sodium channel blocker tetrodotoxin (1 μM) or vehicle (perfusion solution). A total of 2 h after the onset of tetrodotoxin perfusion of the ventral tegmental area, MK-801 (0.1 mg/kg) was injected subcutaneously. Tetrodotoxin perfusion of the ventral tegmental area significantly reduced dialysate levels of dopamine both in the nucleus accumbens and the medial prefrontal cortex to approximately 30% of baseline. When given alone, MK-801 caused a significant, i.e. 50%, increase in extracellular dopamine levels in the nucleus accumbens, and an even larger increase in the medial prefrontal cortex, i.e. 150%. Tetrodotoxin perfusion of the ventral tegmental area completely blocked the systemic MK-801 induced increase in extracellular concentrations of dopamine in the nucleus accumbens. However, the MK-801-evoked increase in dopamine levels in the medial prefrontal cortex was not significantly affected. Thus, the present results allow the conclusion that basal dopamine output in mesolimbic and mesocortical dopamine nerve terminal regions is predominantly dependent on nerve impulses generated in the ventral tegmental area. Moreover, also the MK-801 evoked dopamine release in the mesolimbic projection is almost entirely dependent on the impulse activity of the dopamine neurons, in agreement with our previous results. However, the MK-801 evoked dopamine release in the mesocortical projection is, in contrast, largely independent of the nerve impulse activity in the dopamine cells. The dysfunctions of mesolimbic and mesocortical dopamine neurons induced by systemic administration of non-competitive NMDA receptor antagonists may have direct bearing on the neurobiology of psychotic states, in particular as regards the generation of emotional and cognitive impairments.

Cross-excitation in dorsal root ganglia does not depend on close cell-to-cell apposition.

About 90% of neurons in dorsal root ganglia (DRGs) of rats 2-5 weeks of age are depolarized and excited by impulse activity in neighboring neurons that share the same DRG. Synaptic contacts are extremely rare in DRGs, but instances of close membrane apposition between pairs of neuronal somata are not uncommon, especially in prenatal rats. Close membrane apposition could permit electrotonic interactions among neighboring DRG neurons. We carried out an ultrastructural examination of DRGs taken from rats 2-5 weeks of age and found that by this age < 2% of cells remain in close apposition with neighbors. The remainder are separated by one or two layers of satellite glial cytoplasm. It is, therefore, unlikely that close apposition between adjacent neurons contributes significantly to functional cross-excitation in the DRG.

Effects of β-endorphin on cardiac afferent systems

Studies performed on cats have shown that the antifibrillatory effect of β-endorphin under acute myocardial ischemia is mediated by afferent pathways of the vagus nerves and sympathetic components of arrhythmogenesis. This effect is associated with the ability of β-endorphin to change the impulse activity of cardiovascular and integrative neurons of the nodose ganglion.

Effect of anaesthesia on the impulse activity of thermoregulation centre neurons

Effect of anaesthesia on the impulse activity of thermoregulation centre neurons

Computer Simulations of Neuronal Signal Transduction: The Role of Nonlinear Dynamics and Noise

Nonlinear ionic interactions at the nerve cell membrane can account for oscillating membrane potentials and the generation of periodic neuronal impulse activity. In combination with noise, external modulation of the endogenous oscillations allows for continuous transitions between a variety of impulse patterns. Such "noisy oscillators" afford, thereby, an important mechanism of neuronal encoding as is demonstrated here with experimental data from peripheral cold receptors and corresponding computer simulations.

Interaction between dopamine and glutamate in the sensorimotor cortex during conditioned placing reaction

Changes in impulse activity of sensorimotor cortex neurons associated with interaction of glutamate and dopamine during conditioned placing reaction were investigated in experiments on cats. Application of either glutamate or levodopa as a dopamine precursor increased background and evoked impulse activity in many of sensorimotor cortex neurons. It occurred occasionally that an increased impulse activity of cortical neurons produced by joint application of glutamate and levodopa could be much more intense than that produced by one of these substances. Amphetamine acted on cortical neurons in a similar way as levodopa. Haloperidol, a non-selective blocker of dopamine 1 and dopamine 2 receptors, increased or did not change background and evoked impulse activity in some cortical neurons. In contrast to application of glutamate alone, simultaneous application of glutamate and haloperidol to the neocortex depressed neuronal responses connected with conditioned movement. Thus, glutamate cannot exert its potentiating effect on evoked neuronal activity due to the depressing action of haloperidol. This means that glutamate potentiation is realized to a great extent through molecular mechanisms common for glutamate and dopamine, possibly through G-proteins which are common for glutamate metabotropic and dopamine receptors.

Potent excitatory influence of prefrontal cortex activity on noradrenergic locus coeruleus neurons

An influence of the prefrontal cortex on noradrenergic locus coeruleus neurons would have profound implications for the function of the locus coeruleus system. Although the medial prefrontal cortex does not substantially innervate the core of the nucleus locus coeruleus, evidence indicates that the medial prefrontal cortex projects to regions containing locus coeruleus dendrites; indirect medial prefrontal cortex-locus coeruleus projections are also possible. Here, we examined influences of prefrontal cortex activity on locus coeruleus firing rates by activating or inactivating the medial prefrontal cortex while recording impulse activity of locus coeruleus neurons extracellularly in anaesthetized rats. Most of our electrical stimulation experiments were conducted in rats which underwent lesions of the ascending dorsal bundle of noradrenergic fibres from the locus coeruleus to eliminate locus coeruleus projections to the prefrontal cortex, because antidromic activation of locus coeruleus from the prefrontal cortex affects even non-driven locus coeruleus neurons through collaterals. Single pulse stimulation (1 mA, 0.3-0.5 ms) of the dorsomedial (frontal region 2) or prelimbic region of the medial prefrontal cortex synaptically activated 13/16 (81%) or 16/56 (29%) locus coeruleus neurons, respectively. Train stimulation (20 Hz for 0.5 s) synaptically activated greater percentages of locus coeruleus cells, 11/12 cells (92%) for the dorsomedial prefrontal cortex, and 41150 cells (82%) for the prelimbic cortex. No inhibitory responses in the locus coeruleus were obtained with dorsomedial prefrontal stimulation, and weak inhibition was found in 16% of locus coeruleus cells with prelimbic stimulation. Electrical stimulation of more lateral frontal cortex (Frl area) had no effects on locus coeruleus activity. Chemical stimulation of the dorsomedial prefrontal cortex with l-glutamate (10 or 100 mM) or d, l-homocysteic acid (10 mM) phasically activated 15/26 (55%) locus coeruleus cells, and 15/68 cells (22%) with prelimbic stimulation; such activation was sometimes followed by long-lasting oscillatory activity. No locus coeruleus cells exhibited purely inhibitory responses with chemical stimulation of any prefrontal cortex site. Inactivation of the dorsomedial or prelimbic region of the prefrontal cortex with lidocaine microinjection (2%, 180 or 300 nl) reduced locus coeruleus firing rates in 6/10 (60%) or 7/19 (37%) locus coeruleus cells, respectively. In no case did lidocaine in any prefrontal cortex site activate a locus coeruleus neuron. These results indicate that the medial prefrontal cortex provides a potent excitatory influence on locus coeruleus neurons. The fact that inactivation of the medial prefrontal cortex suppressed locus coeruleus firing indicates that the medial prefrontal cortex also provides a resting tonic excitatory influence on locus coeruleus activity.

Changes of impulse activity of cortical neurons in young SHR

Changes of impulse activity of cortical neurons in young SHR

Effect of Weak Extremely Low Frequency Magnetic Field on Isolated Crayfish Stretch Receptor Neuron: Nonlinear Dependence on Field Amplitude and Frequency

Responses of single mechanoreceptor crayfish neurons to weak extremely low frequency magnetic fields were studied over a wide range of frequencies from 0.001 to 100 Hz, and magnetic fields from 1 to 400 fiT. Observed shifts of neuron impulse activity were weak and variable. They were usually characterized by a slow increase or decrease of spike frequency developing during tens of minutes with markedly variable latencies. Frequency and amplitude “action spectra” were complex, nonlinear, and included several bands (frequency and amplitude “windows”). Neuron response probabilities (if response type and field amplitudes were excluded from consideration) were maximal at 0.001, 0.3, 3, and 60 Hz. They were also maximal at 5, 20, 50, and 300 jaT if field frequencies were not taken into account. Minimal neuron response probabilities were observed at 0.03, 0.8-2, 11-15, and 100 Hz and 1, 10, 30, and 100 /iT, respectively.

Neurophysiological correlates of improvements in cognitive characteristics in monkeys during modification of NMDA-ergic structures of the prefrontal cortex

The effects of modification of NMDA-ergic structures by microdialysis perfusion in the prefrontal cortex (field 8) with NMDA glutamate (2 mM) on visual recognition and short-term memory (STM) were studied in rhesus macaques, using methods based on the deferred differentiation of stimuli of different colors. Impulse activity of neurons in the prefrontal and visual cortex was measured during these experiments, both before and after administration of NMDA. NMDA increased (2-fold) the duration of short-term retention of information and significantly reduced the latent period of the motor response at all delay periods, and also produced significant changes in neuron activity in the prefrontal cortex: depending on the stage of behavior, activity decreased in 60-75% of neurons and increased in 8-26%. NMDA produced significant increases in the cross-correlation coefficients between the responses of neurons in the visual and prefrontal cortex. The results showed that glutaminergic structures in the prefrontal cortex are involved in processes of visual recognition and STM in monkeys. The effect of NMDA, which synchronized cortical neuronal processes, improved the short-term understanding of visual information.

SPONTANEOUS SIGNALLING IN SMALL CENTRAL NEURONS: MECHANISMS AND ROLES OF SPIKE-AMPLITUDE AND SPIKE-INTERVAL FLUCTUATIONS

Spontaneous brain activity is essential for normal brain function. We are studying spontaneous activity in hippocampus at several complexity levels: at the microscopic level by analyzing the role of ion channels, at the mesoscopic level by analyzing the neuronal impulse activity, and at the macroscopic level by computational studies of mean electric fields of cortical network models. We have focused on the role of a subset of hippocampal neurons in the rat--neurons of small size (diameter < 10 microns). The analysis of spontaneous impulse trains in these neurons, both isolated and in slices, show (i) that impulses vary in amplitude, the magnitude depending on the input signal, suggesting that the amplitude variability may play a role in the information processing of the brain, and (ii) that single ion channel events can trigger neuronal impulses, suggesting that these neurons can function as cellular random generators. The possible role of random generators are investigated by simulating spontaneous activity in a cortical network model, based on a simplified description of the architecture of the CA1 area of hippocampus. The simulations show that such random generators can induce synchronous oscillations in cortical networks. These findings highlight the role of microfluctuations for the global macroactivity of the brain, and stress the importance of the study of channel kinetics for brain physiology.

Effects of NMDA receptor blockade in the developing rat somatosensory cortex on the expression of the glia-derived extracellular matrix glycoprotein tenascin-C.

The patterning of synaptic connections during development is thought to be influenced by the correlation of neuronal impulse activity. N-methyl-D-aspartate (NMDA) receptors have been implicated in the reorganization of thalamocortical afferents in the visual system. The topographic mapping of the periphery of sensory systems onto the somatosensory cortex in the whisker-barrel field of rodents has served as another important paradigm in the study of extrinsic influences on synaptic rearrangements. In a search for the molecular cues that may contribute to synaptic plasticity, we have investigated the distribution of the glia-derived extracellular matrix glycoprotein tenascin-C, which is highly expressed during the formation of the barrel field map around birth and delineates the boundaries between barrel fields after segregation of afferent inputs. Here we show that systemic and local application of NMDA receptor antagonists at postnatal day 2 inhibited the down-regulation of tenascin mRNA and protein by postnatal day 6 and prevented the appearance of tenascin-positive barrel field boundaries. Furthermore, barrels were not distinguishable by Nissl staining, and segregation of thalamocortical afferents as monitored by anterograde Dil tracing and acetylcholinesterase histochemistry was not complete. These observations indicate that expression of tenascin-C and segregation of afferent inputs are modified by NMDA receptor-dependent neuronal activity.

Effects of ibogaine, and cocaine and morphine after ibogaine, on ventral tegmental dopamine neurons

Ibogaine, an indole containing alkaloid, has been shown to reduce the rate of injection of morphine and cocaine in self-administration protocols. Since morphine- and cocaine-induced modulation of dopamine release is impulse dependent and essential for their reinforcing effects, disruption of dopamine neuronal activity by ibogaine could explain its purported ‘antiaddictive’ properties. Therefore, the present study was designed to determine: (1) the acute effects of ibogaine on the activity of VTA dopamine neurons, and (2) whether ibogaine pretreatment causes a persistent modification of the dopamine neuronal response to morphine and cocaine. Extracellular recordings in anesthetized animals found that intravenous ibogaine markedly excited VTA dopamine neuronal firing. However, ibogaine pretreatment (6–8 hr and 19 hr before) failed to alter either the spontaneous activity of VTA neurons, or the response of these dopamine neurons to morphine or cocaine. Thus, ibogaine's excitatory effect on VTA neurons is not longlasting nor does it persistently alter cocaine- or morphine-induced changes in dopamine neuron impulse activity. Therefore, other mechanisms must be explored to account for the proposed antiaddictive properties of ibogaine.

Dynamics of the impulse activity of neurons of the neocortex of monkeys in a visual recognition task after brief oxygen deprivation.

Dynamics of the impulse activity of neurons of the neocortex of monkeys in a visual recognition task after brief oxygen deprivation.

Dynamics of the impulse activity of neurons of the neocortex of monkeys in a visual recognition task after brief oxygen deprivation.

A model of brief oxygen supply disruption was created in monkeys trained to a delayed visual spatial choice. A substantial reorganization of the impulse activity of neurons of the visual and prefrontal cerebral cortex, accompanied by disturbances in behavioral reactions, was observed during brief hypoxia (2.5 min); the motor reaction was not restored for several hours in the monkeys during a delayed visual spatial choice. The reorganization of the activity consisted in the appearance of successive phases of hyperactivation and inhibition. The frequency of the impulse activity in the phase of hyperactivation was higher in prefrontal cortex neurons. Successive phases of inhibition and hyperactivation were also identified in the posthypoxic period of restoration in the structure of the activity. The duration of the posthypoxic inhibition and the ratio of the frequencies of posthypoxic hyperactivation to the baseline frequency in the reactions of prefrontal cortex neurons was substantially greater than in the neurons of the visual cortex.