Serotonin and GI Disorders: An Update on Clinical and Experimental Studies

The gastrointestinal (GI) tract is the largest producer of serotonin (5-hydroxytryptamine (5-HT)) in the body, and as such it is intimately connected with GI function and physiology. 5-HT produced by enterochromaffin (EC) cells is an important enteric mucosal signaling molecule and has been implicated in a number of GI diseases, including inflammatory bowel disease and functional disorders such as irritable bowel syndrome. This review will focus on what is known of basic 5-HT physiology and also on the emerging evidence for its novel role in activation of immune response and inflammation in the gut. Utilizing pubmed.gov, search terms such as “5-HT,” “EC cell,” and “colitis,” as well as pertinent reviews, were used to develop a brief overview of EC cell biology and the association between 5-HT and various GI disorders. It is the aim of this review to provide the readers with an update on EC cell biology and current understanding on the role of 5-HT in GI disorders specifically in inflammatory conditions

Transition between Functional Regimes in an Integrate-And-Fire Network Model of the Thalamus

The thalamus is a key brain element in the processing of sensory information. During the sleep and awake states, this brain area is characterized by the presence of two distinct dynamical regimes: in the sleep state activity is dominated by spindle oscillations (7 − 15 Hz) weakly affected by external stimuli, while in the awake state the activity is primarily driven by external stimuli. Here we develop a simple and computationally efficient model of the thalamus that exhibits two dynamical regimes with different information-processing capabilities, and study the transition between them. The network model includes glutamatergic thalamocortical (TC) relay neurons and GABAergic reticular (RE) neurons described by adaptive integrate-and-fire models in which spikes are induced by either depolarization or hyperpolarization rebound. We found a range of connectivity conditions under which the thalamic network composed by these neurons displays the two aforementioned dynamical regimes. Our results show that TC-RE loops generate spindle-like oscillations and that a minimum level of clustering (i.e. local connectivity density) in the RE-RE connections is necessary for the coexistence of the two regimes. We also observe that the transition between the two regimes occurs when the external excitatory input on TC neurons (mimicking sensory stimulation) is large enough to cause a significant fraction of them to switch from hyperpolarization-rebound-driven firing to depolarization-driven firing. Overall, our model gives a novel and clear description of the role that the two types of neurons and their connectivity play in the dynamical regimes observed in the thalamus, and in the transition between them. These results pave the way for the development of efficient models of the transmission of sensory information from periphery to cortex.This work was supported by the European Commission under ITN project NETT (FP7 contract 289146), by the Spanish Ministry of Economy and Competitiveness and FEDER (project FIS2015-66503-C3-1-P1), and by the Generalitat de Catalunya (project 2014SGR0947). A.M. was supported by the NEBIAS European project (EUFP7-ICT-611687), by the PRIN/ HandBot Italian project (CUP: B81J12002680008; prot.: 20102YF2RY), and by the Italian Ministry of Foreign Affairs and International Cooperation, Directorate General for Country Promotion (Economy, Culture and Science) Unit for Scientific and Technological Cooperation, via the Italy-Sweden bilateral research project on "Brain network mechanisms for integration of natural tactile input patterns". J.G.O. also acknowledges support from the ICREA Academia programme and from the "Maria de Maeztu" Programme for Units of Excellence in R&D (Spanish Ministry of Economy and Competitiveness, MDM-2014-0370). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript