Pharmacological characterization of a rat 5-hydroxytryptamine type(3) receptor subunit (r5-HT(3A(b))) expressed in Xenopus laevis oocytes

1. The present study has utilized the two electrode voltage-clamp technique to examine the pharmacological profile of a splice variant of the rat orthologue of the 5-hydroxytryptamine type 3A subunit (5-HT(3A(b))) heterologously expressed in Xenopus laevis oocytes. 2. At negative holding potentials, bath applied 5-HT (300 nM–10 μM) evoked a transient, concentration-dependent (EC(50)=1.1±0.1 μM), inward current. The response reversed in sign at a holding potential of −2.1±1.6 mV. 3. The response to 5-HT was mimicked by the 5-HT(3) receptor selective agonists 2-methyl-5-HT (EC(50)=4.1±0.2 μM), 1-phenylbiguanide (EC(50)=3.0±0.1 μM), 3-chlorophenylbiguanide (EC(50)=140± 10 nM), 3,5-dichlorophenylbiguanide (EC(50)=14.5±0.4 nM) and 2,5-dichlorophenylbiguanide (EC(50)= 10.2±0.6 nM). With the exception of 2-methyl-5-HT, all of the agonists tested elicited maximal current responses comparable to those produced by a saturating concentration (10 μM) of 5-HT. 4. Responses evoked by 5-HT at EC(50) were blocked by the 5-HT(3) receptor selective antagonist ondansetron (IC(50)=231±22 pM) and by the less selective agents (+)-tubocurarine (IC(50)=31.9± 0.01 nM) and cocaine (IC(50)=2.1±0.2 μM). 5. The data are discussed in the context of results previously obtained with the human and mouse orthologues of the 5-HT(3A) subunit. Overall, the study reinforces the conclusion that species differences detected for native 5-HT(3) receptors extend to, and appear largely explained by, differences in the properties of homo-oligomeric receptors formed from 5-HT(3A) subunit orthologues

Dual origins of functionally distinct O-LM interneurons revealed by differential 5-HT3AR expression

Forebrain circuits rely upon a relatively small but remarkably diverse population of GABAergic interneurons to bind and entrain large principal cell assemblies for network synchronization and rhythmogenesis. Despite the high degree of heterogeneity across cortical interneurons, members of a given subtype typically exhibit homogeneous developmental origins, neuromodulatory response profiles, morphological characteristics, neurochemical signatures, and electrical features. Here we report a surprising divergence amongst hippocampal oriens-lacunosum moleculare (O-LM) projecting interneurons that have hitherto been considered a homogeneous cell population. Combined immunocytochemical, anatomical, and electrophysiological interrogation of Htr3a-GFP and Nkx2-1-cre:RCE mice revealed that O-LM cells parse into caudal ganglionic eminence-derived 5-HT(3A)R-expressing, and medial ganglionic eminence- derived 5-HT(3A)R-lacking subpopulations. These two cohorts differentially participate in network oscillations with 5-HT(3A)R-containing O-LM cell recruitment dictated by serotonergic tone. Thus, members of a seemingly uniform interneuron population can exhibit unique circuit functions and neuromodulatory properties dictated by disparate developmental origins

Dissertatio historica de initiis monarchiae Babyloniorum, quam, cum cons. ampliss. Colleg. Philos. in Reg. Acad. Upsal. sub praesidio ... Jacobi Arrhenii ... publico examini modeste subjicit Petrus Hagberg Gestr. In audit. Gustav. maj. ad d. 25. Maji. Anni MDCCV.

International audienceBackground : The incidence of childhood type 1 diabetes (T1D) incidence is rising in many countries, supposedlybecause of changing environmental factors, which are yet largely unknown. The purpose of the study was tounravel environmental markers associated with T1D. Methods : Cases were children with T1D from the French Isis-Diab cohort. Controls were schoolmates or friends ofthe patients. Parents were asked to fill a 845-item questionnaire investigating the child’s environment before diagnosis.The analysis took into account the matching between cases and controls. A second analysis used propensity scoremethods. Results : We found a negative association of several lifestyle variables, gastroenteritis episodes, dental hygiene, hazelnutcocoa spread consumption, wasp and bee stings with T1D, consumption of vegetables from a farm and death of a petby old age. Conclusions : The found statistical association of new environmental markers with T1D calls for replication in othercohorts and investigation of new environmental areas