Glycinergic interneurons are functionally integrated into the inspiratory network of mouse medullary slices

Neuronal activity in the respiratory network is functionally dependent on inhibitory synaptic transmission. Using two-photon excitation microscopy, we analyzed the integration of glycinergic neurons in the isolated inspiratory pre-Bötzinger complex-driven network of the rhythmic slice preparation. Inspiratory (96%) and ‘tonic’ expiratory neurons (4%) were identified via an increase or decrease, respectively, of the cytosolic free calcium concentration during the inspiratory-related respiratory burst. Furthermore, in BAC-transgenic mice expressing EGFP under the control of the GlyT2-promoter, 50% of calcium-imaged inspiratory neurons were glycinergic. Inspiratory bursting of glycinergic neurons in the slice was confirmed by whole-cell recording. We also found glycinergic neurons that receive phasic inhibition from other glycinergic neurons. Our calcium imaging data show that glycinergic neurons comprise a large population of inspiratory neurons in the pre-Bötzinger complex-driven network of the rhythmic slice preparation

Global variation in anastomosis and end colostomy formation following left-sided colorectal resection

Background End colostomy rates following colorectal resection vary across institutions in high-income settings, being influenced by patient, disease, surgeon and system factors. This study aimed to assess global variation in end colostomy rates after left-sided colorectal resection. Methods This study comprised an analysis of GlobalSurg-1 and -2 international, prospective, observational cohort studies (2014, 2016), including consecutive adult patients undergoing elective or emergency left-sided colorectal resection within discrete 2-week windows. Countries were grouped into high-, middle- and low-income tertiles according to the United Nations Human Development Index (HDI). Factors associated with colostomy formation versus primary anastomosis were explored using a multilevel, multivariable logistic regression model. Results In total, 1635 patients from 242 hospitals in 57 countries undergoing left-sided colorectal resection were included: 113 (6·9 per cent) from low-HDI, 254 (15·5 per cent) from middle-HDI and 1268 (77·6 per cent) from high-HDI countries. There was a higher proportion of patients with perforated disease (57·5, 40·9 and 35·4 per cent; P < 0·001) and subsequent use of end colostomy (52·2, 24·8 and 18·9 per cent; P < 0·001) in low- compared with middle- and high-HDI settings. The association with colostomy use in low-HDI settings persisted (odds ratio (OR) 3·20, 95 per cent c.i. 1·35 to 7·57; P = 0·008) after risk adjustment for malignant disease (OR 2·34, 1·65 to 3·32; P < 0·001), emergency surgery (OR 4·08, 2·73 to 6·10; P < 0·001), time to operation at least 48 h (OR 1·99, 1·28 to 3·09; P = 0·002) and disease perforation (OR 4·00, 2·81 to 5·69; P < 0·001). Conclusion Global differences existed in the proportion of patients receiving end stomas after left-sided colorectal resection based on income, which went beyond case mix alone

The peptidergic control circuit for sighing

Sighs are long, deep breaths expressing sadness, relief, or exhaustion. Sighs also occur spontaneously every few minutes to reinflate alveoli, and sighing increases under hypoxia, stress, and certain psychiatric conditions. Here we use molecular, genetic, and pharmacologic approaches to identify a peptidergic sigh control circuit in murine brain. Small neural subpopulations in a key breathing control center (RTN/pFRG) express bombesin-like neuropeptide genes neuromedin B (Nmb) or gastrin releasing peptide (Grp). These project to the preBötzinger Complex (preBötC), the respiratory rhythm generator, which expresses NMB and GRP receptors in overlapping subsets of ~200 neurons. Introducing either neuropeptide into preBötC, or onto preBötC slices, induced sighing, whereas elimination or inhibition of either receptor reduced basal sighing and inhibition of both abolished it. Ablating receptor-expressing neurons eliminated basal and hypoxia-induced sighing, but left breathing otherwise intact initially. We propose these overlapping peptidergic pathways comprise the core of a sigh control circuit that integrates physiological and perhaps emotional input to transform normal breaths into sighs

Prenatal nicotine exposure recruits an excitatory pathway to brainstem parasympathetic cardioinhibitory neurons during hypoxia/hypercapnia in the rat: implications for sudden infant death syndrome.

Maternal cigarette smoking and prenatal nicotine exposure increase the risk for sudden infant death syndrome (SIDS) by 2- to 4-fold, yet despite adverse publicity, nearly one of four pregnant women smoke tobacco. Infants who succumb to SIDS typically experience a severe bradycardia that precedes or is accompanied by centrally mediated life-threatening apneas and gasping. Although the causes of the apnea and bradycardia prevalent in SIDS victims are unknown, it has been hypothesized that these fatal events are exaggerated cardiorespiratory responses to hypoxia or hypercapnia. Changes in heart rate are primarily determined by the activity of cardiac vagal neurons (CVNs) in the brainstem. In this study, we tested whether hypoxia/hypercapnia evokes synaptic pathways to CVNs and whether these cardiorespiratory interactions are altered by pre-natal exposure to nicotine. Spontaneous rhythmic inspiratory-related activity was recorded from the hypoglossal rootlet of 700- to 800-μm medullary sections. CVNs were identified in this preparation by retrograde fluorescent labeling, and excitatory synaptic inputs to CVNs were isolated and studied using patch-clamp electrophysiologic techniques. Hypoxia/hypercapnia did not elicit an increase in excitatory neurotransmission to CVNs in unexposed animals, but in animals that were exposed to nicotine in the prenatal period, hypoxia/hypercapnia recruited an excitatory neurotransmission to CVNs. This study establishes a likely neurochemical mechanism for the exaggerated decrease in heart rate in response to hypoxia/hypercapnia that occurs in SIDS victims. Copyright © 2005 International Pediatric Research Foundation, Inc