Neuronal basis of the slow (<1 Hz) oscillation in neurons of the nucleus reticularis thalami in vitro

During deep sleep and anesthesia, the EEG of humans and animals exhibits a distinctive slow (<1 Hz) rhythm. In inhibitory neurons of the nucleus reticularis thalami (NRT), this rhythm is reflected as a slow (<1 Hz) oscillation of the membrane potential comprising stereotypical, recurring "up" and "down" states. Here we show that reducing the leak current through the activation of group I metabotropic glutamate receptors (mGluRs) with either trans-ACPD [(+/–)-1-aminocyclopentane-trans-1,3-dicarboxylic acid] (50–100 µM) or DHPG [(S)-3,5-dihydroxyphenylglycine] (100 µM) instates an intrinsic slow oscillation in NRT neurons in vitro that is qualitatively equivalent to that observed in vivo. A slow oscillation could also be evoked by synaptically activating mGluRs on NRT neurons via the tetanic stimulation of corticothalamic fibers. Through a combination of experiments and computational modeling we show that the up state of the slow oscillation is predominantly generated by the "window" component of the T-type Ca2+ current, with an additional supportive role for a Ca2+-activated nonselective cation current. The slow oscillation is also fundamentally reliant on an Ih current and is extensively shaped by both Ca2+- and Na+-activated K+ currents. In combination with previous work in thalamocortical neurons, this study suggests that the thalamus plays an important and active role in shaping the slow (<1 Hz) rhythm during deep sleep

The properties of reticular thalamic neuron GABAA IPSCs of absence epilepsy rats lead to enhanced network excitability

Both human investigations and studies in animal models have suggested that abnormalities in GABAA receptor function have a potential role in the pathophysiology of absence seizures. Recently we showed that, prior to seizure onset, GABAA IPSCs in thalamic reticular (NRT) neurons of genetic absence epilepsy rats from Strasbourg (GAERS) had a 25% larger amplitude, a 40% faster decay and a 45% smaller paired-pulse depression than those of nonepileptic control (NEC) rats. By means of a novel mathematical description, the properties of both GAERS and NEC GABAergic synapses can be mimicked. These model synapses were then used in an NRT network model in order to investigate their potential impact on the neuronal firing patterns. Compared to NEC, GAERS NRT neurons show an overall increase in excitability and a higher frequency and regularity of firing in response to periodic input signals. Moreover, in response to randomly distributed stimuli, the GAERS but not the NEC model produces resonance between 7 and 9 Hz, the frequency range of spike–wave discharges in GAERS. The implications of these results for the epileptogenesis of absence seizures are discussed

Muscarinic agonists inhibit the ATP-dependent potassium current and suppress the ventricle-Purkinje action potential dispersion

Activation of the parasympathetic nervous system has been reported to have an antiarrhythmic role during ischemia-reperfusion injury by decreasing the arrhythmia triggers. Furthermore, it was reported that the parasympathetic neurotransmitter acetylcholine is able to modulate the ATP-dependent K-current (IK-ATP), a crucial current activated during hypoxia. However, the possible significance of this current modulation in the antiarrhythmic mechanism is not fully clarified.Action potentials were measured using the conventional microelectrode technique from canine left ventricular papillary muscle and free-running Purkinje fibers, under normal and hypoxic conditions. Ionic currents were measured using the whole-cell configuration of the patch clamp method.5 μM acetylcholine did not influence the action potential duration (APD) either in Purkinje fibers or in papillary muscle preparations. In contrast, it significantly lengthened the APD and suppressed the Purkinje-ventricle APD dispersion when it was administered after 5 μM pinacidil application. 3 μM carbachol reduced the pinacidil-activated IK-ATP under voltage-clamp condition. Acetylcholine lengthened the ventricular action potential under simulated ischemia condition.In this study we found that acetylcholine inhibits the IK-ATP and thus suppresses the ventricle-Purkinje APD dispersion. We conclude that parasympathetic tone may reduce the arrhythmogenic substrate exerting a complex antiarrhythmic mechanism during hypoxic conditions