Spatial heterogeneity enhances and modulates excitability in a mathematical model of the myometrium

The muscular layer of the uterus (myometrium) undergoes profound changes in global excitability prior to parturition. Here, a mathematical model of the myocyte network is developed to investigate the hypothesis that spatial heterogeneity is essential to the transition from local to global excitation which the myometrium undergoes just prior to birth. Each myometrial smooth muscle cell is represented by an element with FitzHugh–Nagumo dynamics. The cells are coupled through resistors that represent gap junctions. Spatial heterogeneity is introduced by means of stochastic variation in coupling strengths, with parameters derived from physiological data. Numerical simulations indicate that even modest increases in the heterogeneity of the system can amplify the ability of locally applied stimuli to elicit global excitation. Moreover, in networks driven by a pacemaker cell, global oscillations of excitation are impeded in fully connected and strongly coupled networks. The ability of a locally stimulated cell or pacemaker cell to excite the network is shown to be strongly dependent on the local spatial correlation structure of the couplings. In summary, spatial heterogeneity is a key factor in enhancing and modulating global excitability

miR-786 Regulation of a Fatty-Acid Elongase Contributes to Rhythmic Calcium-Wave Initiation in \u3cem\u3eC. elegans\u3c/em\u3e

Background: Rhythmic behaviors are ubiquitous phenomena in animals. In C. elegans, defecation is an ultradian rhythmic behavior: every ∼50 s a calcium wave initiating in the posterior intestinal cells triggers the defecation motor program that comprises three sequential muscle contractions. Oscillatory calcium signaling is central to the periodicity of defecation. The posteriormost intestinal cells function as the pacemaker for this rhythmic behavior, although it is unclear how the supremacy of these cells for calcium-wave initiation is controlled. Results: We describe how the loss of the mir-240/786 microRNA cluster, which results in arrhythmic defecation, causes ectopic intestinal calcium-wave initiation. mir-240/786 expression in the intestine is restricted to the posterior cells that function as the defecation pacemaker. Genetic data indicate that mir-240/786 functions upstream of the inositol 1,4,5-trisphosphate (IP3) receptor. Through rescue analysis, it was determined that miR-786 functions to regulate defecation. Furthermore, we identified elo-2, a fatty-acid elongase with a known role in defecation cycling, as a direct target for miR-786. We propose that the regulation of palmitate levels through repression of elo-2 activity is the likely mechanistic link to defecation. Conclusions: Together, these data indicate that miR-786 confers pacemaker status on posterior intestinal cells for the control of calcium-wave initiation through the regulation of elo-2 and, subsequently, palmitate levels. We propose that a difference in fatty-acid composition in the posterior intestinal cells may alter the activities of membrane proteins, such as IP3-receptor or TRPM channels, that control pacemaker activity in the C. elegans intestine

Direct evidence for local oscillatory current sources and intracortical phase gradients in turtle visual cortex

Visual stimuli induce oscillations in the membrane potential of neurons in cortices of several species. In turtle, these oscillations take the form of linear and circular traveling waves. Such waves may be a consequence of a pacemaker that emits periodic pulses of excitation that propagate across a network of excitable neuro-nal tissue or may result from continuous and possibly reconfigu-rable phase shifts along a network with multiple weakly coupled neuronal oscillators. As a means to resolve the origin of wave propagation in turtle visual cortex, we performed simultaneous measurements of the local field potential at a series of depths throughout this cortex. Measurements along a single radial pen-etration revealed the presence of broadband current sources, with a center frequency near 20 Hz ( g band), that were activated by visual stimulation. The spectral coherence between sources at two well-separated loci along a rostral– caudal axis revealed the pres-ence of systematic timing differences between localized cortical oscillators. These multiple oscillating current sources and their timing differences in a tangential plane are interpreted as the neuronal activity that underlies the wave motion revealed in previous imaging studies. The present data provide direct evidence for the inference from imaging of bidirectional wave motion that the stimulus-induced electrical waves in turtle visual cortex corre-spond to phase shifts in a network of coupled neuronal oscillators