Time series models to assess spontaneous activity of somatosensory cortex astrocytes
George Mason University, Virginia, EEUU
The complexity of brain functions can only be approached by a multidisciplinary and comparative approach. The availability of genetically manipulated mammals (mice and rats) and of sophisticated electrophysiological techniques, susceptible of being applied in behaving animals during the acquisition of new motor abilities, have largely facilitated this approach. Our group has studied for years the contribution of sensory, motor, premotor, hippocampal, and prefrontal circuits to non-associative, pavlovian, and instrumental learning paradigms. For this, we have recorded activity dependent changes in strength in cortical and subcortical synapses during the respective acquisition process.
Astrocytes present basal intrinsic activity, although whether this activity is purely spontaneous or regulated by means of unobservable astroglial networks is unclear. To elucidate possible joint firing synchronies, we recorded the basal activity of a cohort of more than 850 somatosensory neocortex astrocytes from P11 mouse models throughout a time lapse of 15 minutes. Their firing activity was assessed through changes of somata Ca2+ concentration. Basal activities were recorded on five independent and equally configured experiments. Each experiment included two neocortical layers simultaneously, accounting for three transitions: layers I and II/III, II/III and IV, and IV and V. Recordings from each experiment were smoothed and normalized before data analysis. Each astrocyte Ca2+ signal was then modeled by an autoregressive moving average model. Coefficients from each astrocyte model were used as inputs to an ensemble clustering approach to segment them into groups with similar activity profiles across time. Results showed different degrees of agreement between experiments and layer transitions. A number of clusters clearly show similar activity profiles, although the spatial distribution of those astrocytes revealed no clear pattern. To test the reliability of the data analysis, six extra experiments, two for each layer transition, were performed afterwards. Within these, an injection of ATP was released to the extracellular medium after 150 seconds. Calcium recordings of almost 400 astrocytes show how all the cells responded synchronously after the injection. Moreover, the analytical workflow correctly clustered astrocytes with similar activation patterns together. The conclusion is that, in the absence of a synchronization source, we found no evidence to back up that basal astrocyte activity exhibits related firing profiles in the neocortex.
Host: Carlos Matute