Time-Frequency characterization of oscillatory calcium signals

Cytosolic calcium signals control a large set of cellular functions. In nerve cells, the role of these intracellular signals is of particular relevance since they can regulate many processes such as synaptic communication, integration of information at the cell body, transcriptional events, neurite growth and formation of neural circuitry. These signals have often complex time courses and information they convey can be coded both in amplitude and frequency. For this reason their quantitative analysis is not easily accomplished and, in particular, it may be difficult to evidence subtle differences in their temporal patterns. In general, spectral analysis is mandatory, but it provides a mean of analysis solely in the space of frequencies. To overcome this limitation we developed new tools based on wavelet analysis in order to extract information on the structure of [Ca2+]i oscillations. In particular we have derived a set of indices by which different [Ca2+]i oscillatory patterns and their change in time can be extracted and quantitatively evaluated. This approach has been validated making use of experimental recordings showing changes in [Ca2+]i oscillatory behavior in chick ciliary ganglion glial cells, stimulated with nicotinic acid adenine dinucleotide phosphate (NAADP), a calcium-releasing agonist. Then we applied this method to the oscillatory response induced in chick ciliary ganglion neurons by basic fibroblast growth factor (bFGF). Moreover we extended this approach including spatial variable inside the analysis, that is we are now able to study [Ca2+]i oscillation in distinct cellular subdomains such as growth cone, neurites and soma. Finally, by means of blockers of TRPC and voltage operated calcium permeable channels, we can provide a characterization in terms of frequency, activity and localization of the different components making up the global signal, coming from each particular channel family.