Impulse Activity Of Neurons Research Articles

Age-Dependent Influence of Cholecystokinin on the Impulse Activity of Neurons in the Dorsomedial and Venromedial Nuclei of the Hypothalamus in Rats

The aim of the work was to analyze the background and induced by the intravenous administration of the cholecystokinin sulfated octapeptide (CCK), as well as the cholecystokinin antagonist proglumide impulse neuronal electrical activity in the dorsomedial (DMN) and ventromedial (VMN) nuclei of the hypothalamus in young (2–3 months), adults (12 months) and aged (24 months) male rats under urethane anesthesia. The mean frequency of background discharges after the injection of CCK in young rats in the DMN significantly decreased from 1.5 ± 0.4 to 0.2 ± 0.1 impulse/s, in the VMN from 2.0 ± 0.4 to 0.9 ± 0.2 impulse/s. Simultaneous administration of CCK and proglumide did not lead to change of frequencies of neuronal activity in this age group. In adult and aged rats, the mean of the background frequency of discharges of neurons in the DMN and VMN was lower than in young rats and did not change significantly under the influence of CCK and proglumide. In DMN and VMN, the most of the neurons were inhibited by CCK, while in DMN the percentage of neurons inhibited by CCK was higher compared to VMN. The DMN of young animals lacked the CCK-activated neurons that appeared in adult and old animals. Thus, this study confirms the elevation theory of aging, which consists in a decrease in the sensitivity of the hypothalamus to homeostatic signals, in particular, hormones that regulate eating behavior.

Age-Related Effect of Cholecystokinin on Impulse Activity of Neurons in the Rat Hypothalamic Dorsomedial and Ventromedial Nuclei

Age-Related Effect of Cholecystokinin on Impulse Activity of Neurons in the Rat Hypothalamic Dorsomedial and Ventromedial Nuclei

The effects of vibration on the neuronal activity of lateral vestibular nuclei in unilaterally labyrinthectomized rats.

Unilateral labyrinthectomy causes distinct oculomotor and postural disorder syndromes that gradually deteriorate. Simultaneously, compensatory mechanisms for the suppression of pathological disorders were activated. The current study aimed to investigate the characteristics of impulse activity in the ipsilateral and contralateral neurons of the lateral vestibular nucleus of unilaterally labyrinthectomized rats during various periods of vibration exposure. A program analysis of the background impulse activity of theneurons in the right- and left-lateral vestibular nuclei of ratsunder normal condition and after right-sided labyrinthectomy was performed. The animals were subjected to different periods of vibration exposure 2days after surgery (5-, 10-, and 15-day periods). A comparison of the characteristics of the background impulse activity of neurons in both nuclei of intact rats revealed an initial asymmetry in the values of the mean impulse frequency and coefficient of variation of interimpulse intervals. After 5days of vibration exposure, the values of the mean impulse frequency of neurons in both Deiters' nuclei were almost equal in labyrinthectomized rats. The mean impulse frequency of neurons on the uninjured side was higher than that on the injured side on the days following vibration exposure. The characteristics and functional significance of the findings are discussed.

Опыт автоматизации физиологических экспериментов

The article describes experiences accumulated over the past decades by I. P. Pavlov Institute of Physiology RAS. They are related to the development and implementation of automation systems for physiological experiments. The article provides examples of developing hardware tools for measuring signals, converting them into digital form, data entry and accumulation to be used on general-purpose computers as well as systems of mini-computers, micro-computers, personal computers and custom-made problem-oriented hardware modules for automating physiological experiments in the main areas of research conducted at Pavlov Institute of Physiology. The article also focuses on the conceptual development of problem-oriented software, data base management systems, and graphical display of results. In particular, it discusses several cases of the development of hardware and software modules for various physiological experiments: modules used in the system for the assessment of the functional state of human respiratory muscles, the examination of contractile function of blood vessels and nodes of the circulatory and lymphatic systems, for monitoring changes in the frequency of impulse activity of neurons, for organizing a controlled electrical effect on a laboratory animal in behavioral experiments, for measuring the vital parameters of laboratory animals in experiments on the mechanisms of visceral pain.

Вплив тромбіну у плазматичному іонному середовищі на розвиток епілептиформної активності культивованих нейронів гіпокампа щурів

The mechanisms of epileptiform neuronal activity develop- ment under blood-brain barrier (BBB) dysfunction remains relevant in modern psychoneurology. In the present work we mimic some effects of BBB disruption in the culture of hip- pocampal neurons to examined the effect of serum-adapted ionic environment on the impulse activity of hippocampal neurons and the role of serum protein thrombin in induction of epileptiform neuronal activity. Using the whole-cell patch- clamp method under current-clamp mode we analyzed the spontaneous action potentials (AP) in the single hippocampal neurons. The changing of ionic extracellular neuronal environ- ment to such serum-adapted contributed to the development of epileptiform tonic activity of cultured hippocampal neurons and led to increase the average APs frequency by 65.1 ± 17.9% (n = 5) in neurons with spontaneous firing activity (FA) and to occurrence of tonic electrical activity (1.65 ± 0.4 s-1) in neurons without firing activity. Glutamate NMDA receptors significantly contribute to epileptiform tonic activity formation in neurons with FA, while their role in tonic activity providing in neurons without FA was insignificant. Thrombin (5 U/ml) in the serum-adapted ionic solution significantly enhanced of epileptiform activity in neurons with and without spontaneous FA: APs frequency increased in these neuronal groups by 117.3 ± 25.6% (n = 3) and by 61.8 ± 11.5% (n = 3), respective- ly, compared with that in the serum-adapted ionic solution only. Blockade of thrombin protease activated receptor 1 (PAR-1) by application of SCH 79797 (10 μm) canceled the thrombin’s effect in neurons without spontaneous FA, and significantly reduced such in neurons with FA. Therefore, the change of ionic extracellular neuronal environment to serum-adapted stimulates the occurrence of epileptiform activity in hippo- campal neurons, that is apparently associated with NMDA- receptors activation in neurons with FA. The proepileptiform action of thrombin was mostly mediated by PAR-1 activation. Thrombin-dependent regulation of the hippocampal single neurons firing activity involves the mechanisms different from the modulation of glutamate NMDA receptors in these cells.

Микроэлектрофизиологическое изучение соотношения возбудительных и тормозных синаптических процессов в кортико-нигральной проекции на модели болезни Паркинсона

The impulse activity of single neurons in substantia nigra pars compacta - SNc (242 neurons, n=11) and substantia nigra pars reticulate - SNr (289 neurons, n=12) under high frequency stimulation of primary motor cortex (M1) was analyzed on 23 white male rats in control and rotenone model of Parkinson’s disease (PD). In SNc neurons in PD model there was no stimulation-induced depression, however, the posttetatic potentiation and depression following the tetanic potentiation, were 1.65 and 2.02 times higher than in control. In control SNr neurons the tetanic potentiation followed by the posttetanic potentiation and depression was 2.37 times higher than the tetanic depression, whereas in the PD model both depression and potentiation levels were subnormal. In PD model, both SNc and SNr neurons exhibited significantly higher spike frequency before and during the stimulation in comparison with control. This indicates the presence of the excitotoxicity accompanied by the neurodegenerative damage followed by the apoptosis and the neuronal death. In SNr neurons both depression and potentiation after the stimulation were much more prominent than in SNc neurons, which indicates that the cortical projections on the SNr are more pronounced. Moreover, the SNc neurons demonstrated higher succeptibility to the pathological changes in the poststimulus depression, leading to the more pronounced potentiation in those neurons in comparison with the SNr neurons, which indicates the more prominent involvement of the former in the PD pathogenesis. In the PD model, with no stimulation-induced depression and more prominent potentiation in the SNc neurons, the SNr neurons maintain the depression and show relatively lowered potentiation, which indicates their lower succeptibility to the excitotoxicity, and the excessive excitability of the remaining neurons as a compensation for the dead ones.

Post-tetanic Potentiation and Depression in Hippocampal Neurons in a Rat Model of Alzheimer’s Disease: Effects of Teucrium Polium Extract

The plant Teucrium polium (T.p.) possesses a wide range of pharmacological activities due to the presence, in particular, of different phytochemicals, phenols and flavonoids. We examined the effects of the T.p. extract on impulse activity of hippocampal neurons in rats with a model of Alzheimer’s disease. Adult albino rats were divided into three groups (5 animals in each). The control group C obtained intracerebroventricular (i.c.v.) infusions of saline, animals of group Aβ were i.c.v. infused with amyloid β peptide 25–35, Aβ(25–35), and group Aβ+T.p. was treated by both Aβ(25–35) infusions and introductions of the T.p. extract. In group Aβ, a greater proportion of hippocampal neurons with post-tetanic depression after high-frequency stimulation of the entorhinal cortex, lower values of the frequency of background activity generated by the above neurons, and relatively weaker modifications of spike activity (post-tetanic potentiation and depression) were observed. Daily administrations of the T.p. extract partially but considerably reversed the above-mentioned negative shifts in spike activity of hippocampal neurons caused by Aβ(25–35). We suggest that T.p. extract containing important phytochemicals is capable of ameliorating the memory dysfunction caused by Aβ(25–35) via blocking amyloid deposition and a positive influence on the functions of hippocampal neurons.

SENSITIVITY OF RAT BRAIN SENSORIMOTOR CORTEX NEURONS TO MEDIATORS IN HEMORRHAGIC STROKE

The problem of post-stress disorders of cerebral circulation, the most severe of which is cerebral hemorrhage, or hemorrhagic stroke, is extremely urgent. Concerning the survival rate, previous studies have shown that in the same type of conflict situations, individuals resistant and predisposed to emotional stressful influences are clearly distinguished. However, the neural mechanisms providing neuromediatory regulation of responses to stressful effects are still little studied. The analysis of neurochemical sensitivity to acetylcholine and norepinephrine of the sensorimotor cortex neurons of rats having different activity according to behavior parameters, i.e., resistance to emotional stress influences before and after experimental hemorrhagic stroke (EHS) was carried out. The recovery process after an EHS due to neural activity in prognostically stable (VA) and predisposed (NA) to stressful situation rats has individual characteristics. Acute stress influence before EHS development changes the nature of neurons activity of the sensorimotor cortex in VA and NA rats on the third and seventh day after EHS. EHS leads to specific changes in the sensitivity of neurons to acetylcholine and norepinephrine in VA and NA rats. Acetylcholine microionophoresis causes activation of the neuron impulse activity in VA and NA rats, and these changes are the same after EHS. Acute stress influence before EHS development does not change nature of neuron responses to norepinephrine microionophoresis in VA animals. On the contrary, in NA rats loss of neuron sensitivity to norepinephrine during EHS development against stress was noted. It is possible that acute stress influence before EHS development can change brain noradrenergic system activity in NA rats, which are prognostically predisposed to stress influences. The data obtained stress the plasticity of the central nervous structure in development of response to stressful influences. (The ethics commission approval protocol number is 18-15 from 13th of Marth 2018.)

Dopamine Release Dynamics in the Tuberoinfundibular Dopamine System.

The relationship between neuronal impulse activity and neurotransmitter release remains elusive. This issue is especially poorly understood in the neuroendocrine system, with its particular demands on periodically voluminous release of neurohormones at the interface of axon terminals and vasculature. A shortage of techniques with sufficient temporal resolution has hindered real-time monitoring of the secretion of the peptides that dominate among the neurohormones. The lactotropic axis provides an important exception in neurochemical identity, however, as pituitary prolactin secretion is primarily under monoaminergic control, via tuberoinfundibular dopamine (TIDA) neurons projecting to the median eminence (ME). Here, we combined electrical or optogenetic stimulation and fast-scan cyclic voltammetry to address dopamine release dynamics in the male mouse TIDA system. Imposing different discharge frequencies during brief (3 s) stimulation of TIDA terminals in the ME revealed that dopamine output is maximal at 10 Hz, which was found to parallel the TIDA neuron action potential frequency distribution during phasic discharge. Over more sustained stimulation periods (150 s), maximal output occurred at 5 Hz, similar to the average action potential firing frequency of tonically active TIDA neurons. Application of the dopamine transporter blocker, methylphenidate, significantly increased dopamine levels in the ME, supporting a functional role of the transporter at the neurons' terminals. Lastly, TIDA neuron stimulation at the cell body yielded perisomatic release of dopamine, which may contribute to an ultrafast negative feedback mechanism to constrain TIDA electrical activity. Together, these data shed light on how spiking patterns in the neuroendocrine system translate to vesicular release toward the pituitary and identify how dopamine dynamics are controlled in the TIDA system at different cellular compartments.SIGNIFICANCE STATEMENT A central question in neuroscience is the complex relationship between neuronal discharge activity and transmitter release. By combining optogenetic stimulation and voltammetry, we address this issue in dopamine neurons of the neuroendocrine system, which faces particular spatiotemporal demands on exocytotic release; large amounts of neurohormone need to be secreted into the portal capillaries with precise timing to adapt to physiological requirements. Our data show that release is maximal around the neurons' default firing frequency. We further provide support for functional dopamine transport at the neurovascular terminals, shedding light on a long-standing controversy about the existence of neuroendocrine transmitter reuptake. Finally, we show that dopamine release occurs also at the somatodendritic level, providing a substrate for an ultrashort autoregulatory feedback loop.

Regulation of Action Potential Frequency and Amplitude by T-type Ca2+ Channel During Spontaneous Synchronous Activity of Hippocampal Neurons

In this paper, the changes in the frequency and amplitude of action potentials (AP) were investigated depending on the depolarization caused by the Ca2+ channels activity during the spontaneous synchronous activity (SSA) of hippocampal neurons in culture. It is known that the pacemaker neuronal electrical activity can be both tonic and bursting. Using the image analysis to measure [Са2+]i and patch-clamp to register the membrane potential we show that depolarization caused by the GABA(A) receptor inhibitor results in a pattern of SSA in which tonic APs frequency of 2−3 Hz are generated by a neuron without any changes in cytosolic free Ca2+ concentration, ([Ca2+]i). The tonic mode is interrupted by bursts activity, which is accompanied by slow depolarization and calcium pulses. The inhibitor of T-type calcium channels, ML218, suppresses this process. The frequency and amplitude of the AP are regulated by slow depolarization pulses as follows: on the depolarization front, the APs frequency increases. At the same time, the amplitude decreases due to Na+ channels inactivation. The higher is the depolarization rate, the higher is the APs frequency. If slow depolarization amplitude exceeds Na+ channels reactivation potential, the neuronal impulse activity stops. As the [Ca2+]i increases and Ca2+-dependent K+ channels are activated, depolarization amplitude decreases slowly, and Na+ channels are reactivated, which leads to a gradual increase in the amplitude of APs against the background of depolarization decrease. The frequency of APs on the backside of depolarization pulse slows down to 3–4 Hz due to the occurrence of the faster Ca2+-potential oscillations (micro bursts of AP). Under these conditions, only one AP can be generated due to rapid depolarization at the leading edge. After that, APs generation is suppressed due to Na+ channel inactivation. The frequency of APs in this case coincides with the Ca2+ channel activation frequency (3−4 Hz). The burst firing is terminated due to [Ca2+]i increase, Ca2+-dependent K+ channels activation, and voltage-gated Ca2+ channels (VGCC) inactivation. As a result, the membrane is hyperpolarized even more (10 mV lower than the critical potential), that suppress AP generation, activate HCN-like channels and reactivate Na+ and VGCC. The activity of HCN-like channels increases, the membrane slowly depolarizes and reaches the threshold potential. The generation of tonic APs begins, and then, the Ca2+ channels opens, and Ca2+ potential and Ca2+ signal induced again. Thus, the Ca2+-channels, is determining the pulse of slow depolarization, control the frequency and the amplitude of APs during SSA, regulating the activation and inactivation conditions of Na+ channels. The T-type channels inhibitors reduce the duration of burst firing and Ca2+ impulse in neurons in vitro, stimulating their survival during hyperexcitation and ischemia. Thus, reducing the Ca2+ pulse duration caused by the inhibitors of T-type Ca2+-channels, can be one of the reasons for the known neuroprotective effect of these compounds. Keywords: spontaneous synchronous activity of neurons, calcium signal, T-type calcium channels, voltage-gated calcium channels, action potential, genesis of bursting activity, action potential bursts, depolarization shift, critical potential

Cortical spreading depression in migraine-time to reconsider?

New evidence concerning the pathophysiology of migraine has come from the results of therapeutic transcranial magnetic stimulation (tTMS). The instantaneous responses to single pulses applied during the aura or headache phase, together with a number of other observations, make it unlikely that cortical spreading depression is involved in migraine. tTMS is considered to act by abolishing abnormal impulse activity in cortical pyramidal neurons and a suggestion is made as to how this activity could arise.

USING THE SERIAL RAMP RECORDINGS FOR RAPID TESTING OF THE GENERATING ABILITY OF IMPULSE ACTIVITY OF ISOLATED HIPPOCAMPAL NEURONS

In this study we investigated changes of impulse activity of hippocampal neurons of the hippocampus by using ramp recordings. We have described the usage of serial ramp recordings of neuronal electrical activity for rapid testing of the generating ability of isolated hippocampal neurons. An analysis of the data has shown that the proposed protocol of serial ramp recordings allows to define additional characteristics of the neuronal impulse activity: (i) the thresholds for initiation of generation and suppression of the generation, (ii) the shape and amplitude of relationship between the interpulse intervals and neuronal depolarizations. The suggested stimulation protocols and related analysis are tools that can be effectively used to justify influence of chemicals or other experimental factors on the impulse activity of neurons.

Individual differences and vulnerability to drug addiction: a focus on the endocannabinoid system.

Vulnerability to drug addiction depends upon the interactions between the biological makeup of the individual, the environment, and age. These interactions are complex and difficult to tease apart. Since dopamine is involved in the rewarding effects of drugs of abuse, it is postulated that innate differences in mesocorticolimbic pathway can influence the response to drug exposure. In particular, higher and lower expression of dopamine D2 receptors in the ventral striatum (i.e. a marker of dopamine function) has been considered a putative protective and a risk factor, respectively, that can influence one's susceptibility to continued drug abuse as well as the transition to addiction. This phenomenon, which is phylogenetically preserved, appears to be a compensatory change to increased impulse activity of midbrain dopamine neurons. Hence, dopamine neuronal excitability plays a fundamental role in the diverse stages of the drug addiction cycle. In this review, a framework for the evidence that modulation of dopamine neuronal activity plays in the context of vulnerability to drug addiction will be presented. Furthermore, since endogenous cannabinoids serve as retrograde messengers to shape afferent neuronal activity in a short- and long-lasting fashion, their role in individual differences and vulnerability to drug addiction will be discussed.

A subpopulation of neurochemically-identified ventral tegmental area dopamine neurons is excited by intravenous cocaine.

Systemic administration of cocaine is thought to decrease the firing rates of ventral tegmental area (VTA) dopamine (DA) neurons. However, this view is based on categorizations of recorded neurons as DA neurons using preselected electrophysiological characteristics lacking neurochemical confirmation. Without applying cellular preselection, we recorded the impulse activity of VTA neurons in response to cocaine administration in anesthetized adult rats. The phenotype of recorded neurons was determined by their juxtacellular labeling and immunohistochemical detection of tyrosine hydroxylase (TH), a DA marker. We found that intravenous cocaine altered firing rates in the majority of recorded VTA neurons. Within the cocaine-responsive neurons, half of the population was excited and the other half was inhibited. Both populations had similar discharge rates and firing regularities, and most neurons did not exhibit changes in burst firing. Inhibited neurons were more abundant in the posterior VTA, whereas excited neurons were distributed evenly throughout the VTA. Cocaine-excited neurons were more likely to be excited by footshock. Within the subpopulation of TH-positive neurons, 36% were excited by cocaine and 64% were inhibited. Within the subpopulation of TH-negative neurons, 44% were excited and 28% were inhibited. Contrary to the prevailing view that all DA neurons are inhibited by cocaine, we found a subset of confirmed VTA DA neurons that is excited by systemic administration of cocaine. We provide evidence indicating that DA neurons are heterogeneous in their response to cocaine and that VTA non-DA neurons play an active role in processing systemic cocaine.

Time characteristics of impulse activity of neurons with the V-shaped frequency receptive fields in the house mouse (Mus musculus) auditory midbrain

Time characteristics of impulse activity of neurons with the V-shaped frequency receptive fields in the house mouse (Mus musculus) auditory midbrain

Correlation between brain stem aminergic neuronal activity and EEG patterns in a wakeful cat

There was carried out a correlation analysis for the frequency of the background impulse activity of the brain stem monoaminergic neurons and the spectral power of electroencephalogram frequency components in a wakeful cat. The frequency of the background impulse activity in the studied neurons was found to be reliably (p < 0.05) correlated with all basic electroencephalogram rhythms. Among the statistically significant correlations, there were most often observed the positive ones between the background impulse activity of the ventral tegmentum dopaminergic neurons and the locus coeruleus noradrenergic neurons, on the one hand, and the power spectral density of alpha-rhythm, on the other hand (40.3% and 48.0% respectively). Besides, 47.7% of the raphe nuclei serotoninergic neurons under study showed positive correlation between their impulse activity and the spectral power density of beta-rhythm. The results obtained let us assume the possibility of taking specific EEG patterns as markers of activity for the basic cerebral monoaminergic systems.

Adaptation of differential sensitivity of auditory system neurons to amplitude modulation after abrupt change of signal level

Impulse activity of neurons of brainstem auditory nuclei (medulla dorsal nucleus and midbrain torus semicircularis) of the grass frog (Rana temporaria) was recorded under action of long amplitude-modulated tonal signals. After adaptation of neuronal response to acting stimulus (30–60 s after its onset), we performed a sharp change (by 20–40 dB) of the mean signal level with preservation of unchanged frequency and depth of modulation. We also recorded a change of density impulsation and of degree of its synchronization with the modulation period as well as the phase of maximum reaction at the modulation period and phase of the response every 2 or 4 s. In the adapted state, the sharp change of the mean level had been provided, while maintaining frequency and depth unchanged. During the adaptation to long signals with small modulation indexes the firing rate continuously decreased, but synchronization with envelope usually increased considerably. A sharp rise in the mean level resulted in an increase of firing rate, which could be accompanied either by a continuation of synchronization growth (the effect is more typical of the dorsal nucleus) or by a sharp fall in synchrony with its subsequent slow recovery (the effect is more typical of the torus semicircularis). Nature of the changes following the change of the intensity of the reaction could depend on the signal parameters (initial level, magnitude of the jump, frequency and depth of modulation). The connection between the observed physiological data and the psychophysics of differential intensity coding is discussed.

Prenatal Stress Exposure Increases the Excitation of Dopamine Neurons in the Ventral Tegmental Area and Alters Their Reponses to Psychostimulants

Prenatal stress exposure (PSE) is known to increase addiction risk. Dopamine (DA) neurons in the ventral tegmental area (VTA) play an important role in addiction. In order to understand the cellular mechanisms underlying PSE-induced increase in addiction risk, we examined the effects of PSE on the electrical impulse activity of VTA DA neurons using the in vivo extracellular single-unit recording technique. Amphetamine self-administration was also conducted to confirm increased addiction risk after PSE. The PSE was carried out by restraining pregnant dams from GD 11 to 20. Adult male offspring (3-6 months old) were used in the experiments. Animals with PSE showed enhanced amphetamine self-administration compared with controls when amphetamine dose was reduced after acquisition. The number of spontaneously active VTA DA neurons was also reduced in PSE rats. The reduction was reversed by acute apomorphine that normally inhibits the impulse activity of DA neurons. The reversal effect suggests that PSE-induced reduction in the number of spontaneously active VTA DA neurons is caused by overexcitation to the extent of depolarization block. Furthermore, the reduced number of spontaneously active VTA DA neurons was also reversed by acute psychostimulants (eg, amphetamine; cocaine), which in control rats inhibited the activity of VTA DA neurons. The reversal effect on VTA DA neuron in PSE animals represents an actual increase in the impulse activity. This effect might contribute to increased responding to psychostimulants and mediate increased addiction risk after PSE.

Atomoxetine modulates spontaneous and sensory-evoked discharge of locus coeruleus noradrenergic neurons

Atomoxetine (ATM) is a potent norepinephrine (NE) uptake inhibitor and increases both NE and dopamine synaptic levels in prefrontal cortex, where it is thought to exert its beneficial effects on attention and impulsivity. At the behavioral level, ATM has been shown to cause improvements on the measures of executive functions, such as response inhibition, working memory and attentional set shifting across different species. However, the exact mechanism of action for ATM's effects on cognition is still not clear. One possible target for the cognitive enhancing effects of ATM is the noradrenergic locus coeruleus (LC), the only source of NE to key forebrain areas such as cerebral cortex and hippocampus. Although it is known that ATM increases NE availability overall by blocking reuptake of NE, the effects of this agent on impulse activity of LC neurons have not been reported. Here, the effect of ATM (0.1–1 mg/kg, ip) on NE-LC neurons was investigated by recording extracellular activity of LC neurons in isoflurane-anesthetized rats. ATM caused a significant decrease of the tonic activity of LC single-units, although leaving intact the sensory-evoked excitatory component of LC phasic response. Moreover, the magnitude of the inhibitory component of LC response to paw stimulation was increased after 1 mg/kg of ATM and its duration was prolonged at 0.3 mg/kg. Together, these effects of ATM produced an increase in the phasic-to-tonic ratio of LC phasic response to sensory stimulation. ATM also modulated the average sensory-evoked local field potential (LFP) and spike-field coherence in LC depending on the dose tested. The lower dose (0.1 mg/kg) significantly decreased early positive and negative components of the sensory-evoked LFP response. Higher doses (0.3–1 mg/kg) initially increased and then decreased the amplitude of components of the evoked fields, whereas the spike-field coherence was enhanced by 1 mg/kg ATM across frequency bands. Finally, coherence between LC fields and EEG signals was generally increased by 1 mg/kg ATM, whereas 0.1 and 0.3 mg/kg respectively decreased and increased coherence values in specific frequency bands. Taken together these results suggest that ATM effects on LC neuronal activity are dose-dependent, with different doses affecting different aspects of LC firing. This modulation of activity of LC-NE neurons may play a role in the cognitive effects of ATM.This article is part of a Special Issue entitled ‘Cognitive Enhancers’.

Effect of stimulation of β adrenoreceptors on conditioned reflex-related spike activity of neurons of the cat somatosensory cortex

Using extracellular recording of impulse activity of pyramidal neurons of the cat somatosensory cortex generated in the course of realization of an operant conditioned reflex, we examined effects of microiontophoretic applications of an agonist of β2 adrenoreceptors, metaproterenol, and of an antagonist of β adrenoreceptors, propranolol, on the frequency of this impulsation. Applications of propranolol induced intensification of both background and reflex-related spiking. The effect of metaproterenol was manifested as moderate intensification of background discharges, a noticeable increase in the frequency of evoked impulsation, and an increase in the latency of impulse reactions. It is supposed that noradrenergic projections to the neocortex intensify neuronal activity via activation of β2 adrenoreceptors and suppress this activity via influencing mostly β1 adrenoreceptors. Such effects of synaptically active agents should probably be taken into account in the treatment of neurological diseases, namely epilepsy, neurodegenerative disorders, psychoemotional shifts, etc., which are accompanied by emotional and cognitive disorders.