THE EFFECT OF THROMBIN IN THE SERUM-ADAPTED IONIC ENVIRONMENT ON THE INDUCTION OF EPILEPTIFORM FIRING ACTIVITY OF HIPPOCAMPAL CULTURED NEURONS

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.

Tonic activity in lateral habenula neurons promotes disengagement from reward-seeking behavior

SUMMARYSurvival requires both the ability to persistently pursue goals and the ability to determine when it is time to stop, an adaptive balance of perseverance and disengagement. Neural activity in the lateral habenula (LHb) has been linked to aversion and negative valence, but its role in regulating the balance between reward-seeking and disengaged behavioral states remains unclear. Here, we show that LHb neural activity is tonically elevated during minutes-long disengagements from reward-seeking behavior, whether due to repeated reward omission or following sufficient consumption of reward. Further, we show that LHb inhibition extends ongoing reward-seeking behavioral states but does not prompt re-engagement. We find no evidence for similar tonic activity fluctuations in ventral tegmental area (VTA) dopamine neurons. Our findings implicate the LHb as a key mediator of disengagement from reward-seeking behavior in multiple contexts and argue against the idea that the LHb contributes to decisions solely by signaling aversion.

Preeclampsia is not associated with elevated muscle sympathetic reactivity.

Objective: To determine whether increased chemoreflex tonic activity is associated with augmented muscle sympathetic nervous sys activity (MSNA) in women diagnosed with preeclampsia. Methods: Women with preeclampsia (n=19; 32±5 years old, 31±3 weeks gestation) were matched by age and gestational age with pregnant women (controls, n=38, 32±4 years old, 31±4 weeks gestation; 2:1 ratio). MSNA (n=9 preeclampsia) was assessed during baseline, peripheral chemoreflex de-activation (hyperoxia) and a cold pressor test (CPT). Baroreflex gain, diastolic blood pressure at which there is a 50% likelihood of MSNA occurring (T50) and plasma noradrenaline concentrations were measured. Results: Baseline mean arterial pressure (MAP: 106±11 vs. 87±10 mmHg, p<0.0001), noradrenaline concentrations (498±152 pg/mL vs. 326±147, p=0.001) and T50 (79±7 vs. 71±9 mmHg, p=0.02) were greater in women with preeclampsia compared to controls. However, baseline MSNA (burst incidence [BI]: 41±16 vs. 45±13 bursts/100hb, p=0.4) was not different between groups. Responses to hyperoxia (ΔBI -5±7 vs. -1±8 bursts/100hb, p=0.1; ΔMAP -1±3 vs. -2±3 mmHg, p=0.7) and CPT (ΔBI 15±7 vs. 12±11 bursts/100hb, p=0.6; ΔMAP 10±4 vs. 12±11 mmHg, p=0.6) were not different between groups. Conclusion: Our findings question the assumption that increased MSNA contributes to hypertension in women with preeclampsia. The chemoreflex does not appear to contribute to an increase in MSNA in women with preeclampsia.

Tonic firing mode of midbrain dopamine neurons continuously tracks reward values changing moment-by-moment

Appropriate actions are taken based on the values of future rewards. The phasic activity of midbrain dopamine neurons signals these values. Because reward values often change over time, even on a subsecond-by-subsecond basis, appropriate action selection requires continuous value monitoring. However, the phasic dopamine activity, which is sporadic and has a short duration, likely fails continuous monitoring. Here, we demonstrate a tonic firing mode of dopamine neurons that effectively tracks changing reward values. We recorded dopamine neuron activity in monkeys during a Pavlovian procedure in which the value of a cued reward gradually increased or decreased. Dopamine neurons tonically increased and decreased their activity as the reward value changed. This tonic activity was evoked more strongly by non-burst spikes than burst spikes producing a conventional phasic activity. Our findings suggest that dopamine neurons change their firing mode to effectively signal reward values, which could underlie action selection in changing environments.

Viral bronchiolitis and the detrimental effects of sleep

Infants recovering from bronchiolitis and no longer requiring supplemental oxygen will have brief episodes of oxygen desaturation during sleep when monitored with pulse oximetry. These episodes can be explained by the inhibition of the tonic activity of the inspiratory muscles during rapid eye movement sleep. Pulse oximetry monitoring should be discontinued, and these infants considered for discharge.

TONIC ACTIVITY AND GRAVITATIONAL CONTROL OF THE POSTURAL MUSCLE

The review is an attempt to describe and give a meaning to the accumulated data about the mechanisms controlling the structure and functionality of the postural muscle the almost continuous work of which makes it possible for the humans and animals to exist actively on Earth's surface. A great bulk of these data was obtained, described and systematized by professor I.B. Kozlovskaya and her pupils. A body of the most interesting facts and regularities was documented in other laboratories and research centers, quite often under the influence of ideas suggested by I.B. Kozlovskaya. The concept of the tonic system, that is, an integral physiological apparatus comprising not only slow and fast muscular fibers and small controlling motoneurons but also a complex of the brain (up to and including the striatum and motor cortex) and sensory mechanisms, constitutes the most important parts of her theoretical legacy. The fundamental conclusion of this review is that the gravity-dependent tonic contracting activity of the postural muscle controlled by the nervous system and afferent mechanisms is key to maintaining its structure, signal pathways and mechanic properties crucial for its constant anti-gravity activity.