Role In Rhythm Generation Research Articles

Circadian clocks: A cry in the dark?

Cryptochrome proteins are key components of the circadian systems of both Drosophila and mammals. In Drosophila, they appear to be responsible for the entrainment of the circadian clock by the light–dark cycle, while in mammals they perform an important role in rhythm generation itself.

Calcium currents in respiratory neurons of the cat in vivo.

Under in vivo conditions, periodic burst discharges of medullary respiratory neurons of mature cat typically start with a rebound depolarization when inhibition through antagonistic neurons stops. This rebound can be blocked by ionophoretically applied extracellular Cd2+. A similar Cd(2+)-sensitive rebound depolarization is triggered by hyperpolarizing current pulses even in the presence of extracellular tetrodotoxin (TTX) and tetraethylammonium (TEA). In current-clamp mode, the current/voltage (I/V) curves rectify outwardly at positive voltages, and this rectification is blocked by Cd2+. Intracellular injection of the L-type Ca(2+)-channel blocker methoxy-verapamil changes the spontaneous activity patterns of neurons. In those neurons that typically show augmenting patterns, the membrane depolarization is slowed down, while in those neurons that have a declining pattern, voltage changes become augmenting. Voltage-clamp measurements reveal a transient, low-voltage-activated T-type Ca2+ current. The current is deinactivated at -100 mV and almost completely inactivated at -60 mV. Depolarizing voltage commands starting from more positive holding potentials evoke sustained Ca2+ currents that reach a maximum at 0 mV. The sustained L-type Ca2+ currents are completely blocked by extracellular Cd2+. We conclude that low- and high-voltage-activated Ca2+ currents are expressed in all types of respiratory neurons and play an essential role in rhythm generation and pattern formation in adult cats in vivo.

NMDA receptor-mediated oscillatory properties: potential role in rhythm generation in the mammalian spinal cord.

Previous studies have demonstrated that (1) NMDA receptor activation occurs during locomotor network operation in lower and higher vertebrates and (2) NMDA induces active membrane properties that can be expressed as intrinsic voltage fluctuations in cells located in the spinal cord of lower vertebrates, as well as in neurons located in supraspinal regions of the mammalian nervous system. This paper reviews recent data showing that NMDA can induce similar inherent membrane potential behavior in synaptically isolated motoneurons and interneurons in the mammalian (in vitro neonatal rat) spinal cord. These TTX-resistant voltage fluctuations include rhythmic oscillations and plateau potentials, as well as low-frequency long-lasting voltage shifts (LLVSs). 5-HT facilitates the transformation of LLVSs into oscillatory events, and 5-HT receptor antagonists have the reverse effect. In the absence of TTX, locomotor-related rhythmic drive potentials in spinal cord neurons can display nonlinear voltage behavior compatible with NMDA receptor activation, although other voltage-activated conductances are not excluded. Suppression of the nonlinear voltage response associated with NMDA receptor activation, via removal of Mg2+, disrupts locomotor patterns of network activity. The potential role of NMDA receptor activation in the operation of mammalian locomotor networks is discussed in the context of these recent observations.

Oscillating Networks: Control of Burst Duration by Electrically Coupled Neurons.

The pyloric network of the stomatogastric ganglion in crustacea is a central pattern generator that can produce the same basic rhythm over a wide frequency range. Three electrically coupled neurons, the anterior burster (AB) neuron and two pyloric dilator (PD) neurons, act as a pacemaker unit for the pyloric network. The functional characteristics of the pacemaker network are the result of electrical coupling between neurons with quite different intrinsic properties, each contributing a basic feature to the complete circuit. The AB neuron, a conditional oscillator, plays a dominant role in rhythm generation. In the work described here, we manipulate the frequency of the AB neuron both isolated and electrically coupled to the PD neurons. Physiological and modeling studies indicate that the PD neurons play an important role in regulating the duration of the bursts produced by the pacemaker unit.