Phasic Component Research Articles

Central and peripheral contributions to dynamic changes in nucleus accumbens glucose induced by intravenous cocaine.

The pattern of neural, physiological and behavioral effects induced by cocaine is consistent with metabolic neural activation, yet direct attempts to evaluate central metabolic effects of this drug have produced controversial results. Here, we used enzyme-based glucose sensors coupled with high-speed amperometry in freely moving rats to examine how intravenous cocaine at a behaviorally active dose affects extracellular glucose levels in the nucleus accumbens (NAc), a critical structure within the motivation-reinforcement circuit. In drug-naive rats, cocaine induced a bimodal increase in glucose, with the first, ultra-fast phasic rise appearing during the injection (latency 6–8 s; ~50 μM or ~5% of baseline) followed by a larger, more prolonged tonic elevation (~100 μM or 10% of baseline, peak ~15 min). While the rapid, phasic component of the glucose response remained stable following subsequent cocaine injections, the tonic component progressively decreased. Cocaine-methiodide, cocaine's peripherally acting analog, induced an equally rapid and strong initial glucose rise, indicating cocaine's action on peripheral neural substrates as its cause. However, this analog did not induce increases in either locomotion or tonic glucose, suggesting direct central mediation of these cocaine effects. Under systemic pharmacological blockade of dopamine transmission, both phasic and tonic components of the cocaine-induced glucose response were only slightly reduced, suggesting a significant role of non-dopamine mechanisms in cocaine-induced accumbal glucose influx. Hence, intravenous cocaine induces rapid, strong inflow of glucose into NAc extracellular space by involving both peripheral and central, non-dopamine drug actions, thus preventing a possible deficit resulting from enhanced glucose use by brain cells.

Action Regulation Introducing Stress Management Techniques and High Performance in Soccer

Fifty-two high performing soccer players of South-East Asian contingent were selected by three expert soccer instructors on the basis of their consistent high performance and on the basis of their performance on psychomotor and psychobiological parameters. All of these players were subjected to pre-intervention analyses of Sc orienting reflex indices (phasic components of electrodermal activity) as well as sympathovagal activity based on HRV indices which were assessed simultaneously while the players were engaged in psychomotor reaction ability performances. Structural equations were done to identify the path regression related to performance excellence, which were suggestive of incoherence between the predictors. Short-term intensive self-regulation as well as action-regulation training modules was developed to foster ideomotor orientation in the players, which however was found effective in modification of the intrinsic psychobiological mechanism leading towards excellence in performance in the high-performer soccer players. Thus they were randomly categorised into four groups, comprising of one no-intervention control group (N = 13); experimental group I (N = 13) who received action-regulation training; experimental group II (N = 13), who received training of electromyography (EMG) biofeedback, and experimental group III (N = 13), who received combined training of action - regulation and electromyography (EMG) biofeedback (for 15 min.s/day, for 3 days per week, for 12 weeks). Repeated measure of ANOVA and multiple linear and polynomial regression analyses along with the predictive structural analyses were done to identify relationships between the psychobiological processes, in relation to the cognitive-affective and affective-motivational aspects of sports behaviour, revealed by the projective analyses of emotionality. These models were aptly able to explain the efficacy of the action-regulation intervention techniques, in inducing the cognitive flexibility and emotional resilience required for performance excellence in elite-level soccer players.

Electrodermal activity in bipolar patients during affective elicitation.

Bipolar patients are characterized by a pathological unpredictable behavior, resulting in fluctuations between states of depression and episodes of mania or hypomania. In the current clinical practice, the psychiatric diagnosis is made through clinician-administered rating scales and questionnaires, disregarding the potential contribution provided by physiological signs. The aim of this paper is to investigate how changes in the autonomic nervous system activity can be correlated with clinical mood swings. More specifically, a group of ten bipolar patients underwent an emotional elicitation protocol to investigate the autonomic nervous system dynamics, through the electrodermal activity (EDA), among different mood states. In addition, a control group of ten healthy subjects were recruited and underwent the same protocol. Physiological signals were analyzed by applying the deconvolutive method to reconstruct EDA tonic and phasic components, from which several significant features were extracted to quantify the sympathetic activation. Experimental results performed on both the healthy subjects and the bipolar patients supported the hypothesis of a relationship between autonomic dysfunctions and pathological mood states.

The rate of change of vergence-accommodation conflict affects visual discomfort.

Stereoscopic (S3D) displays create conflicts between the distance to which the eyes must converge and the distance to which the eyes must accommodate. Such conflicts require the viewer to overcome the normal coupling between vergence and accommodation, and this effort appears to cause viewer discomfort. Vergence-accommodation coupling is driven by the phasic components of the underlying control systems, and those components respond to relatively fast changes in vergence and accommodative stimuli. Given the relationship between phasic changes and vergence-accommodation coupling, we examined how the rate of change in the vergence-accommodation conflict affects viewer discomfort. We used a stereoscopic display that allows independent manipulation of the stimuli to vergence and accommodation. We presented stimuli that simulate natural viewing (i.e., vergence and accommodative stimuli changed together) and stimuli that simulate S3D viewing (i.e., vergence stimulus changes but accommodative stimulus remains fixed). The changes occurred at 0.01, 0.05, or 0.25 Hz. The lowest rate is too slow to stimulate the phasic components while the highest rate is well within the phasic range. The results were consistent with our expectation: somewhat greater discomfort was experienced when stimulus distance changed rapidly, particularly in S3D viewing when the vergence stimulus changed but the accommodative stimulus did not. These results may help in the generation of guidelines for the creation and viewing of stereo content with acceptable viewer comfort.

Activity-dependent sensory signal processing in mechanically responsive slowly conducting meningeal afferents.

Activity-dependent processes in slowly conducting afferents have been shown to modulate conduction and receptive properties, but it is not known how the frequency of action potential firing determines the responses of such fibers to mechanical stimulation. We examined the responses of slowly conducting meningeal afferents to mechanical stimuli and the influence of preceding action potential activity. In hemisected rat heads with adhering cranial dura mater, recordings were made from meningeal nerves. Dural receptive fields of mechanically sensitive afferent fibers were stimulated with a custom-made electromechanostimulator. Sinusoidal mechanical stimuli of different stimulus durations and amplitudes were applied to produce either high-frequency (phasic) or low-frequency (tonic) discharges. Most fibers showed slowing of their axonal conduction velocity on electrically evoked activity at ≥2 Hz. In this state, the peak firing frequency of phasic responses to a 250-ms mechanical stimulus was significantly reduced compared with control. In contrast, the frequency of tonic responses induced by mechanical stimuli of >500 ms did not change. In a rare subtype of afferents, which showed conduction velocity speeding during activity, an increase in the phasic responses to mechanical stimuli was observed. Depending on the axonal properties of the afferent fibers, encoding of phasic components of mechanical stimuli is altered according to the immediate firing history. Preceding activity in mechanoreceptors slowing their conduction velocity seems to provide a form of low-pass filtering of action potential discharges predominantly reducing the phasic component. This may improve discrimination between harmless and potentially harmful mechanical stimuli in normal tissue.

Electrodermal activity processing: a convex optimization approach.

This paper reports on a novel model based on convex optimization methods for the analysis of the skin conductance (SC) as response of the electrodermal activity (EDA) to affective stimuli. Starting from previous assessed methodological approaches, this new model proposes a decomposition of SC into tonic and phasic components through the solution of a convex optimization problem. Previous knowledge about the physiology of the EDA is accounted for by means of an appropriate choice of constraints and regularizers. In order to test the effectiveness of the new approach, an experimental session in which 9 healthy subjects were stimulated using affective pictures gathered from the IAPS database was designed and carried out. The experimental session included series of negative-valence high-arousal images and series of neutral images, with an inter-stimulus interval of about 2 seconds for both neutral and high arousal pictures. Next, a statistical analysis was performed on a set of features extracted from the phasic driver and the tonic signal estimated by the model. Results showed that the phasic driver extracted from the model was able to strongly distinguish arousal sessions from neutral ones. Conversely, no significant difference was found for the tonic components. This experimental findings are consistent with the literature and confirm that the phasic component is strictly related to changes in the sympathetic activity of the autonomic nervous system. Although preliminary, these results are very encouraging and future work will progress to further validate the model through specific and controlled experiments.

Influence of acute treatment with sibutramine on the sympathetic neurotransmission of the young rat vas deferens

The effects of acute treatment with sibutramine on the peripheral sympathetic neurotransmission in vas deferens of young rats were still not evaluated. Therefore, we carried out this study in order to verify the effects of acute sibutramine treatment on the neuronal- and exogenous agonist-induced contractions of the young rat vas deferens. Young 45-day-old male Wistar rats were pretreated with sibutramine 6mg/kg and after 4h the vas deferens was used for experiment. The acute treatment with sibutramine was able to increase the potency (pD2) of noradrenaline and phenylephrine. Moreover, the efficacy (Emax) of noradrenaline was increased while the efficacy of serotonin and nicotine were decreased. The maximum effect induced by a single concentration of tyramine was diminished in the vas deferens from treated group. Moreover, the leftward shift of the noradrenaline curves promoted by uptake blockers (cocaine and corticosterone) and β-adrenoceptor antagonist (propranolol) was reduced in the vas deferens of treated group. The initial phasic and secondary tonic components of the neuronal-evoked contractions of vas deferens from treated group at the frequencies of 2Hz were decreased. Moreover, only the initial phasic component at 5Hz was diminished by the acute treatment with sibutramine. In conclusion, we showed that the acute treatment with sibutramine in young rats was able to affect the peripheral sympathetic nervous system by inhibition of noradrenaline uptake and reduction of the neuronal content of this neurotransmitter, leading to an enhancement of vas deferens sensitivity to noradrenaline.

Low-dose combination of Rho kinase and L-type Ca2+ channel antagonists for selective inhibition of depolarization-induced sustained arterial contraction

L-type Ca2+ channels (LTCCs) are involved in the maintenance of tonic arterial contractions and regulate the RhoA/Rho-associated kinase (ROCK) sensitization cascade. We have tested effects of individual and combined low concentrations of LTCCs and ROCK inhibitors to produce arterial relaxation without the adverse side effects of LTCCs antagonists. We have also studied whether this pharmacological strategy alters Ca2+-dependent electrical properties of isolated arterial and cardiac myocytes as well as cardiac contractility. Rat basilar, human carotid and coronary arterial rings were mounted on a small-vessel myograph to measure isometric tension and cardiac contractility was measured in Langendorff-perfused rat heart. Simultaneous cytosolic Ca2+ concentration and arterial diameter were measured in intact pressurized arteries loaded with Fura-2. Patch-clamp techniques were used to measure electrical properties in isolated cardiac and arterial myocytes. Low concentrations of LTCCs and ROCK inhibitors reduced the tonic component of moderate depolarization-evoked contraction, leaving the phasic component practically unaltered. This selective vasorelaxant effect was more marked when the LTCCs and ROCK inhibitors were applied together. In the concentration range used (nM), Ca2+ currents in arterial myocytes, cardiac action potentials and heart contractility were unaffected by this pharmacological approach. In conclusion, low doses of LTCCs and ROCK inhibitors could be used to selectively relax precontracted arteries in pathologic conditions such as hypertension, and cerebral or coronary spasms with minor side effects on physiological contractile properties of vascular and cardiac myocytes.

Tetra-acetylajugasterone a new constituent of Vitex cienkowskii with vasorelaxant activity

Tetra-acetylajugasterone C (TAAC) was found to be one of the naturally occurring compounds of the Cameroonian medicinal plant Vitex cienkowskii which is responsible for a vasorelaxant activity of an extract of this plant. The evaluation of the underlying mechanisms for the relaxing effect of TAAC was determined using aortic rings of rats and mice. TAAC produced a concentration-dependent relaxation in rat artery rings pre-contracted with 1μM noradrenaline (IC50: 8.40μM) or 60mM KCl (IC50: 36.30μM). The nitric oxide synthase inhibitor l-NAME (100μM) and the soluble guanylate cyclase inhibitor ODQ (10μM) significantly attenuated the vasodilatory effect of TAAC. TAAC also exerted a relaxing effect in aorta of wild-type mice (cGKI+/+; IC50=13.04μM) but a weaker effect in aorta of mice lacking cGMP-dependent protein kinase I (cGKI−/−; IC50=36.12μM). The involvement of calcium channels was studied in rings pre-incubated in calcium-free buffer and primed with 1μM noradrenaline prior to addition of calcium to elicit contraction. TAAC (100μM) completely inhibited the resulting calcium-induced vasoconstriction. The same concentration of TAAC showed a stronger effect on the tonic than on the phasic component of noradrenaline-induced contraction. This study shows that TAAC, a newly detected constituent of Vitex cienkowskii contributes to the relaxing effect of an extract of the plant. The effect is partially mediated by the involvement of the NO/cGMP pathway of the smooth muscle but additionally inhibition of calcium influx into the cell may play a role.

Time-dependent expression of hypertonic effects on bullfrog taste nerve responses to salts and bitter substances

We previously showed that the hypertonicity of taste stimulating solutions modified tonic responses, the quasi-steady state component following the transient (phasic) component of each integrated taste nerve response. Here we show that the hypertonicity opens tight junctions surrounding taste receptor cells in a time-dependent manner and modifies whole taste nerve responses in bullfrogs. We increased the tonicity of stimulating solutions with non-taste substances such as urea or ethylene glycol. The hypertonicity enhanced phasic responses to NaCl>0.2M, and suppressed those to NaCl<0.1M, 1mM CaCl2, and 1mM bitter substances (quinine, denatonium and strychnine). The hypertonicity also enhanced the phasic responses to a variety of 0.5M salts such as LiCl and KCl. The enhancing effect was increased by increasing the difference between the ionic mobilities of the cations and anions in the salt. A preincubation time >20s in the presence of 1M non-taste substances was needed to elicit both the enhancing and suppressing effects. Lucifer Yellow CH, a paracellular marker dye, diffused into bullfrog taste receptor organs in 30s in the presence of hypertonicity. These results agreed with our proposed mechanism of hypertonic effects that considered the diffusion potential across open tight junctions.

Activity-Dependent Potentiation of an Asynchronous Component of GABA-ergic Synaptic Currents in Cultured Hippocampal Neurons

After stimulation of GABA-ergic synaptic connections in a culture of hippocampal neurons by a series of depolarizing current pulses (5-45 sec-1, 5-20 stimuli), an inhibitory postsynaptic current (IPSC) consisting of a phasic component and an asynchronous component develops in the postsynaptic neuron. In experiments with simultaneous recording from two synapticaly connected neurons, we found that 2-min-long depolarization of the presynaptic cell to +40 mV also led to the development of the asynchronous IPSC component (аIPSC) induced by a single action potential (AP) in the presynaptic neuron. In this case, the decay time of IPSC was, on average, three times greater than in the first case. Analogous potentiation of аIPSC was observed in a part of the synaptic connections after their longlasting (15 min) stimulation by series of depolarizing current pulses (45 sec-1, 20 stimuli, betweenseries intervals 23 sec). Such potentiation of аIPSC was preserved for a long time (from 3 to 17 min). Simultaneously with potentiation of аIPSC, we observed potentiation of plateau-like inward current through the membrane of the presynaptic neuron in some synaptic connections. The charge transferred by this current through the membrane of the presynaptic cell correlated significantly with the decay time of evoked IPSC in the postsynaptic neuron (mean correlation coefficient 0.83±0.10). This fact can be considered an indication that the above-mentioned inward current mediates potentiation of the above IPSC. The obtained data allow us to hypothesize that the above-described form of plasticity can regulate the efficacy of GABA-ergic synaptic transmission in the hippocampus in the physiological modes of synaptic activity.

Corroborative Psychobiological Indices Explaining Young Adolescent Emotionality

Purpose of this present study was to identify the intricate nature of disruptive emotionality observed in young adolescent athletes of Malaysia. Twenty six male young competitive athletes volunteered as participants, who were subjected to evaluation of self report indices of subjective experiences of transient mood states; inner psychobiological status (autonomic orienting response habituation) and projective analyses of emotionality (in the form of evaluation indices of resilience, constriction rigidity). Findings indicated corroborative relationships between differential psychobiological and mood states measures in predicting inner core emotionality. Dispositional emotional characteristics such as - excitability, resilience and constriction as well as tonic and phasic components of skin conductance activity were found aptly predicted by differential extents of transient facilitative, inhibitive, positive as well as negative mood state measures and faster orienting latency, which have provided us with a framework of corroborative emotional make –up. Attempts were made to identify the deep-rooted affective motivational and perceptual-cognitive as well as cognitive-emotional aspects related to perceived sense of competence as well as the subjective feelings of apprehension of loosing observed in the young athletes. Corroborative psychophysiological markers for innate psychological make-up was attempted to be established. Multiple linear and polynomial regression analyses were done which however suggested differential possibilities of direct, inverse and supportive relationships between decomposition of autonomic orienting activity components related to cognitive-affective and affective- motivational aspects of sports behaviour.

Frequency dependence of excitation–contraction of multicellular smooth muscle preparations: the relevance to bipolar electrosurgery

BackgroundBipolar electrosurgical tissue welding uses forceps-like electrodes for grasping the tissues and delivering high-frequency electric current (HFEC) to produce local heat, desiccation, and protein denaturation, resulting in the fusion of the contacting tissues. Although in this technique no electric current is flowing through the whole body to cause electric injury, depending on the frequency of applied energy, it may produce local excitation of intramural nerves, which can propagate beyond the surgical site potentially causing harmful effects. Materials and methodsThe effects of varying frequency of HFEC on tissue excitability in bipolar electrosurgical modality were studied in vitro using electric field stimulation (EFS) method on multicellular smooth muscle strips of rat vas deferens. Contractile response to 5-s-long sine wave EFS train was taken as the measure of excitation of intramural nerves. ResultsEFS-induced contraction consisted of phasic and tonic components. The amplitude of both components decreased with increasing frequency, with tonic component disappearing at about 10 kHz and phasic component at about 50 kHz. Because components of EFS-induced contraction depend on different neurotransmitters, this indicates that various neurotransmitter systems are characterized by distinct frequency dependence, but above 50 kHz they all become inactivated. Bipolar electrosurgical sealing of porcine gut showed no difference in the structure of seal area at HFEC of 67 and 533 kHz. ConclusionsEFS frequency of 50 kHz represents the upper limit for excitation. HFEC above 50 kHz is safe to use for bipolar electrosurgical tissue welding without concerns of excitation propagating beyond the surgical site.

Human hypoglossal motor unit activities in exercise

The genioglossus (GG) muscle is considered the principal protruder muscle of the tongue that dilates and stiffens the pharyngeal airway. We recorded whole muscle and single motor unit (MU) activities in healthy adults performing progressive intensity exercise on a cycle ergometer. Tungsten microelectrodes were inserted percutaneously into the GG of 11 subjects (20-40 years) to record electromyographic (EMG) activities and pulmonary ventilation (VI) at rest and at workload increments up to 300 W. Increases in respiratory drive were associated with increases in VI, mean inspiratory flow (Vt/Ti) and tonic and phasic components of the GG EMG activity. In contrast, individual MUs typically showed expiration-related decreases in firing as exercise intensity increased. We suggest the decrease in MU activity may occur secondary to afferent feedback from lungs/chest wall and that compensation for more negative inspiratory airway pressures generated during heavy exercise occurs primarily via recruitment of previously silent MUs.

Short-Latency Afferent Inhibition Modulation during Finger Movement

When somatosensory input via electrical stimulation of a peripheral nerve precedes a transcranial magnetic stimulation (TMS) pulse over the primary motor cortex (M1) the corticospinal output is substantially reduced, a phenomenon known as short-latency afferent inhibition (SAI). The present study investigated SAI during rest and during pre-movement, phasic and tonic components of movement. Participants were required to perform an index finger flexion reaction time task in response to an auditory cue. In a series of experiments, SAI was evoked from the mixed, median nerve at the wrist or the cutaneous, digital nerve stimulation of the index finger. To assess the spinal versus cortical origin of movement-related modulation of SAI, F-wave amplitudes were measured during rest and the three movement components. Results indicated that SAI was reduced during all movement components compared to rest, an effect that occurred for both nerves stimulated. Pre-movement SAI reduction was primarily attributed to reduced cortical inhibition, while increased spinal excitability additionally contributed to reduced SAI during tonic and phasic components of movement. SAI was differentially modulated across movement components with mixed but not cutaneous nerve stimulation. These findings reveal that SAI is reduced during movement and this reduction begins as early as the preparation to move. Further, these data suggest that the degree of SAI reduction during movement may be specific to the volume and/or composition of afferent input carried by each nerve.

Fourier Transform Analysis of Rabbit Detrusor Autonomous Contractions Reveals Length Dependent Increases in Tone and Slow Wave Development at Long Lengths

Bladder wall muscle (detrusor) develops low amplitude rhythmic contractions. Low amplitude rhythmic contraction activity is increased in detrusor from patients with overactive bladder. In this in vitro study we used fast Fourier transforms to assess the length dependence of low amplitude rhythmic contraction components. Rabbit detrusor strips were placed in a muscle bath between 2 clips to adjust length and record isometric tension. Tissues stretched from 70% to 130% of a reference muscle length at 10% increments were allowed to develop low amplitude rhythmic contractions at each length for 20 minutes. Low amplitude rhythmic contraction data were analyzed using fast Fourier transforms and represented by a frequency rather than a time spectrum. Based on fast Fourier transform analysis summarized by signal peaks within specific frequency ranges, rabbit low amplitude rhythmic contraction waveforms were divided into 1 tonic and 2 phasic components, defined as A0 + A1F1 + A2F2, where A0 is a length dependent basal tonic component that increases linearly, A1F1 is a slow wave with a length dependent specific amplitude (A1) and a length independent constant frequency (F1) of approximately 11.2 Hz, and A2F2 is a fast wave with a length dependent amplitude (A2) and frequency (F2) of approximately 0.03 Hz. Fast Fourier transform analysis revealed that rabbit low amplitude rhythmic contractions consist of a basal tonic component plus 2 phasic components. The amplitude of all 3 components was length dependent. The frequency of the fast component was not length dependent and the slow component was absent at short muscle lengths, developing only at muscle lengths beyond that producing a maximum active contraction.

Synaptic Ribbons Influence the Size and Frequency of Miniature-like Evoked Postsynaptic Currents

Nonspiking cells of several sensory systems respond to stimuli with graded changes in neurotransmitter release and possess specialized synaptic ribbons. Here, we show that manipulations to synaptic ribbons caused dramatic effects on mEPSC-like (mlEPSC) amplitude and frequency. Damage to rod-bipolar cell ribbons using fluorophore-assisted light inactivation resulted in the immediate reduction of mlEPSC amplitude and frequency, whereas the first evoked response after damage remained largely intact. The reduction in amplitude could not be recovered by increasing release frequency after ribbon damage. In parallel experiments, we looked at mlEPSCs from cones of hibernating ground squirrels, which exhibit dramatically smaller ribbons than awake animals. Fewer and smaller mlEPSCs were observed postsynaptic to cones from hibernating animals, although depolarized cones were able to generate larger mlEPSCs. Our results indicate that ribbon size may influence mlEPSC frequency and support a role for ribbons in coordinating multivesicular release.

Monoterpene α-thujone exerts a differential inhibitory action on GABAA receptors implicated in phasic and tonic GABAergic inhibition

A monoterpene ketone, α-thujone originally attracted attention as a major natural ingredient of absinthe and was suspected to cause adverse effects such as hallucinations and seizures in persons excessively consuming this beverage. Although subsequent studies ruled out any major role of α-thujone in the “absynthism”, it was found that at high doses it may induce epileptic activity pointing to an interaction with GABAergic inhibition. Indeed, subsequent studies, including those from this laboratory, showed that α-thujone inhibits GABAergic currents. However, GABAA receptors are extremely heterogeneous and in the present study we have investigated the effect of α-thujone on different recombinant GABAA receptors (α1β2γ2L, α1β2, α1β2δ and α4β2δ) relevant to phasic or tonic forms of inhibition. We report that α-thujone inhibits all considered receptor types by a qualitatively similar mechanism but the strongest effect is observed for α1β2δ receptors, suggesting that tonic currents might be more sensitive to α-thujone than the phasic ones. Moreover, we demonstrate that tonic currents, mimicked by response to a submicromollar GABA concentration (0.3μM) in cultured neurons, showed a substantially larger sensitivity to α-thujone than responses elicited by higher [GABA] (more similar to phasic currents) or Inhibitory Postsynaptic Currents in the same preparation. Importantly, the extent of tonic current inhibition by α-thujone was as strong as in the case of currents mediated by α1β2δ receptors. Altogether, these data provide evidence that different GABAA receptor subtypes show distinct sensitivities to α-thujone and suggest that this compound may differentially affect tonic and phasic components of GABAergic inhibition.

Phasic Mesolimbic Dopamine Release Tracks Reward Seeking During Expression of Pavlovian-to-Instrumental Transfer

Recent theories addressing mesolimbic dopamine's role in reward processing emphasize two apparently distinct functions, one in reinforcement learning (i.e., prediction error) and another in incentive motivation (i.e., the invigoration of reward seeking elicited by reward-paired cues). Here, we evaluate the latter. Using fast-scan cyclic voltammetry, we monitored, in real time, dopamine release in the nucleus accumbens core of rats (n = 9) during a Pavlovian-to-instrumental transfer task in which the effects of a reward-predictive cue on an independently trained instrumental action were assessed. Voltammetric data were parsed into slow and phasic components to determine whether these forms of dopamine signaling were differentially related to task performance. We found that a reward-paired cue, which increased reward-seeking actions, induced an increase in phasic mesolimbic dopamine release and produced slower elevations in extracellular dopamine. Interestingly, phasic dopamine release was temporally related to and positively correlated with lever-press activity generally, while slow dopamine changes were not significantly related to such activity. Importantly, the propensity of the reward-paired cue to increase lever pressing was predicted by the amplitude of phasic dopamine release events, indicating a possible mechanism through which cues initiate reward-seeking actions. These data suggest that those phasic mesolimbic dopamine release events thought to signal reward prediction error may also be related to the incentive motivational impact of reward-paired cues on reward-seeking actions.

Зміни експресії гена c-fos в ядрах мигдалеподібного тіла та частоти серцевих скорочень при реалізації їжодобувних стереотипних рухів у щурів

The distribution of Fos-immunoreactive (Fos-ir) and NADPH Diaphorase reactive (NADPH-dr-) neurons in the different subnuclei of amygdala and insular cortex (on the level -2,12 to -3,14 mm from bregma), and the associated changes of heart rate (HR) in intact, food-deprivated and executed food-procuring movements of rats were studied. In comparison with other groups of animals, the mean number of the Fos-ir neurons in the central nucleus of amygdala (Ce) and the insular cortex (GI/DI) at all studied levels was significantly greater in the executed food-procuring movements in rats. The main focus of localization of the Fos-ir neurons was found in lateral part of the Ce (58.5 +/- 1.9 units in 40-microm-thick section) at the level -2.56 mm. The mean number of Fos-ir neurons was significantly greater also in the lateral and capsular parts of the Ce. The mean number of Fos-ir neurons in the GI/DI was 165.5 +/- 3.2 cells in section. The number and density of NADPH-d reactive neurons was not significantly different in the brain structures of all animal groups studied. The double stained neurons (Fos-ir + NADPH-dr) were registered in medial, basolateral, anterior cortical amygdaloid nuclei and substantia innominata (SI) in rats after realization food-procuring movements. It was found that realization of food-procuring movements by the forelimb during repeated sessions was accompanied with the gradual decline of mean values of the HR (from 5% to 12% of control level) with subsequent renewal of them to the initial values (tonic component). The analysis of dynamics of the HR changes during realization of separate purposeful motion has shown the transient period of the HR suppression (500 ms), which coincided with the terminal phase of grasping of food pellet (phasic component). We suggest that the revealed focuses of localization of Fos-ir neurons in the lateral and medial subregions of amigdaloid Ce and also GI/DI, and SI testified that these structures of brain are involved in generation of the goal-directed motions. Direct projections of these subnuclei (and hypothalamus) to the cardiovascular centers of the medulla determine the associated regulation of the cardiovascular system function in the period of realization of the goal-directed motions in animals.