Differentielle Modulation spannungsabhängiger Ca2+-Leitfähigkeiten in identifizierten Motoneuronen eines definierten neuronalen Netzwerks
Zusammenfassung der Projektergebnisse
In neurons, Ca2+ regulates a multitude of cellular functions, and many aspects of information processing in single neurons are dependent on highly localized calcium domains. Besides being a charge carrier, which contributes directly to the membrane potential, calcium serves as a second messenger that controls a variety of cellular processes including synaptic release, membrane excitability, enzyme activation and activity-dependent gene activation. Selective activation of these functions is achieved through the spatial and temporal distribution of the calcium signals. The spatio-temporal Ca2+ dynamics are determined by several cellular parameters, including: the calcium influx, the geometry of the cell, the location of the calcium source, the calcium buffering, the calcium extrusion and the locally changing diffusion coefficients. Our long term goal is to better understand how intracellular Ca2+ dynamics contribute to neuronal function. Here, using combined electrophysiological and optical recordings we analyzed two aspects of neuron-type specific, cellular mechanisms and parameters that determine the spatio-temporal Ca2+ dynamics. 1) In identified neurons of the lobster pyloric network, which has very successfully served as a model to study general principles of rhythmic motor pattern generation and cellular mechanisms of neuromodulation, we showed that dopamine (DA) modifies voltage-activated Ca2+ accumulation in synaptic varicosities of identified neurons in ways that are consistent with DA’s effects on synaptic transmission: DA elevates Ca2+ accumulation in LP and PY varicosities, and reduces Ca2+ accumulation in PD varicosities. However, in all three neuron types, we also found varicosities that were unaffected by DA. In the PY neurons, we found that DA can simultaneously increase and decrease voltage-evoked Ca2+ accumulation at different varicosities, even within the same neuron. These results suggest that regulation of Ca2+ entry is a common mechanism to regulate synaptic strength in the pyloric network. However, voltage-evoked local Ca2+ accumulation can be differentially modulated to control Ca2+-dependent processes in functionally separate compartments of a single neuron. 2) Using patch-clamp recordings and fast optical imaging in combination with the ‘added buffer approach’, we analyzed the Ca2+ handling properties of different identified neuron types in the insect olfactory system. With its many functional and structural similarities to the vertebrate olfactory system, the insect olfactory system served as an excellent model to investigate general mechanisms of olfactory information processing. Our focus was on two types of local interneurons (LNs) with significant differences in intrinsic electrophysiological properties: (1) spiking LNs that generate ‘normal’ Na+ driven action potentials and (2) nonspiking LNs that do not express voltage-activated Na+ channels. We found that the distinct electrophysiological properties from different types of central olfactory interneurons are strongly correlated with their cell specific calcium handling properties: non-spiking LNs, in which Ca2+ is the only cation that enters the cell to contribute to membrane depolarization, had the highest endogenous Ca2+ binding ratio and Ca2+ extrusion rate.
Projektbezogene Publikationen (Auswahl)
- Heterogeneous effects of dopamine on highly localized, voltage-induced Ca2+ accumulation in identified motoneurons. J Neurophysiol 98: 2910-2917, 2007
loppenburg P, Zipfel WR, Webb WW, and Harris-Warrick RM
- Differences of Ca2+ handling properties in identified central olfactory neurons of the antennal lobe. Cell Calcium 46: 87-98, 2009
Pippow A, Husch A, Pouzat C, and Kloppenburg P
- Quantitative estimation of calcium dynamics from ratiometric measurements: a direct, nonratioing method. J Neurophysiol 103: 1130-1144, 2010
Joucla S, Pippow A, Kloppenburg P, and Pouzat C
