Spiking Patterns and Their Functional Implications in the Antennal Lobe of the Tobacco Hornworm Manduca sexta

Bursting as well as tonic firing patterns have been described in various sensory systems. In the olfactory system, spontaneous bursts have been observed in neurons distributed across several synaptic levels, from the periphery, to the olfactory bulb (OB) and to the olfactory cortex. Several in vitro studies indicate that spontaneous firing patterns may be viewed as “fingerprints” of different types of neurons that exhibit distinct functions in the OB. It is still not known, however, if and how neuronal burstiness is correlated with the coding of natural olfactory stimuli. We thus conducted an in vivo study to probe this question in the OB equivalent structure of insects, the antennal lobe (AL) of the tobacco hornworm Manduca sexta. We found that in the moth's AL, both projection (output) neurons (PNs) and local interneurons (LNs) are spontaneously active, but PNs tend to produce spike bursts while LNs fire more regularly. In addition, we found that the burstiness of PNs is correlated with the strength of their responses to odor stimulation – the more bursting the stronger their responses to odors. Moreover, the burstiness of PNs was also positively correlated with the spontaneous firing rate of these neurons, and pharmacological reduction of bursting resulted in a decrease of the neurons' responsiveness. These results suggest that neuronal burstiness reflects a physiological state of these neurons that is directly linked to their response characteristics

Computational Model of the Insect Pheromone Transduction Cascade

A biophysical model of receptor potential generation in the male moth olfactory receptor neuron is presented. It takes into account all pre-effector processes—the translocation of pheromone molecules from air to sensillum lymph, their deactivation and interaction with the receptors, and the G-protein and effector enzyme activation—and focuses on the main post-effector processes. These processes involve the production and degradation of second messengers (IP3 and DAG), the opening and closing of a series of ionic channels (IP3-gated Ca2+ channel, DAG-gated cationic channel, Ca2+-gated Cl− channel, and Ca2+- and voltage-gated K+ channel), and Ca2+ extrusion mechanisms. The whole network is regulated by modulators (protein kinase C and Ca2+-calmodulin) that exert feedback inhibition on the effector and channels. The evolution in time of these linked chemical species and currents and the resulting membrane potentials in response to single pulse stimulation of various intensities were simulated. The unknown parameter values were fitted by comparison to the amplitude and temporal characteristics (rising and falling times) of the experimentally measured receptor potential at various pheromone doses. The model obtained captures the main features of the dose–response curves: the wide dynamic range of six decades with the same amplitudes as the experimental data, the short rising time, and the long falling time. It also reproduces the second messenger kinetics. It suggests that the two main types of depolarizing ionic channels play different roles at low and high pheromone concentrations; the DAG-gated cationic channel plays the major role for depolarization at low concentrations, and the Ca2+-gated Cl− channel plays the major role for depolarization at middle and high concentrations. Several testable predictions are proposed, and future developments are discussed

Fontan-Associated Liver Disease (FALD) in the EUROFontan experience: an insight into European awareness

Fontan-Associated Liver Disease (FALD) is a dramatically emerging problem even if not precisely defined in term of debated diagnosis and surveillance protocols. We analyze FALD prevalence, clinical impact and implications in a European cohort of patients. It's a retrospective observational multicenter study including Fontan patients operated between 1990 and 2022. Anatomical, clinical, surgical and liver-related data were collected, defining FALD as a spectrum of time-related structural-functional liver modifications due to congestive hepatopathy (from mild liver fibrosis to liver cirrhosis and hepatocellular carcinoma) diagnosed through multiparametric evaluations. 14 centers routinely conducted liver assessment after Fontan completion. Out of 2141 patients, 343 (16%) were diagnosed with FALD (M/F = 198/145; median age 18 years, IQR 15-26) with a median follow-up time of 14 years (IQR 9-20) from Fontan surgery. Among these, there were 19 (5.5%) deaths, 5 (26.3%) of whom related to advanced liver disease/cancer. FALD showed no significant association with gender (p = 0.4, adjusted p-value = 0.5), dominant ventricular morphology (p = 0.060, adjusted p-value = 0.086) nor surgery type (p = 0.3, adjusted p-value = 0.4). Significant association emerged between FALD and fenestration absence (p = 22 kPa on transient elastography (p < 0.001, adjusted p-value < 0.001). The analysis demonstrated no significant association between FALD and abnormal liver function tests (p = 0.2), heart transplantation (p = 0.6, adjusted p-value = 0.6), worse survival (p = 0.38). This study shows significant mortality related to FALD, which is also associated to clinical signs of failing Fontan circulation, stressing the pressing need of universally shared diagnostic criteria and surveillance protocols, to prevent and/or early-identify FALD and its more lethal complications.Thoracic Surger