Nanomolar oxytocin synergizes with weak electrical afferent stimulation to activate the locomotor CPG of the rat spinal cord in vitro.

Synergizing the effect of afferent fibre stimulation with pharmacological interventions is a desirable goal to trigger spinal locomotor activity, especially after injury. Thus, to better understand the mechanisms to optimize this process, we studied the role of the neuropeptide oxytocin (previously shown to stimulate locomotor networks) on network and motoneuron properties using the isolated neonatal rat spinal cord. On motoneurons oxytocin (1 nM-1 \u3bcM) generated sporadic bursts with superimposed firing and dose-dependent depolarization. No desensitization was observed despite repeated applications. Tetrodotoxin completely blocked the effects of oxytocin, demonstrating the network origin of the responses. Recording motoneuron pool activity from lumbar ventral roots showed oxytocin mediated depolarization with synchronous bursts, and depression of reflex responses in a stimulus and peptide-concentration dependent fashion. Disinhibited bursting caused by strychnine and bicuculline was accelerated by oxytocin whose action was blocked by the oxytocin antagonist atosiban. Fictive locomotion appeared when subthreshold concentrations of NMDA plus 5HT were coapplied with oxytocin, an effect prevented after 24 h incubation with the inhibitor of 5HT synthesis, PCPA. When fictive locomotion was fully manifested, oxytocin did not change periodicity, although cycle amplitude became smaller. A novel protocol of electrical stimulation based on noisy waveforms and applied to one dorsal root evoked stereotypic fictive locomotion. Whenever the stimulus intensity was subthreshold, low doses of oxytocin triggered fictive locomotion although oxytocin per se did not affect primary afferent depolarization evoked by dorsal root pulses. Among the several functional targets for the action of oxytocin at lumbar spinal cord level, the present results highlight how small concentrations of this peptide could bring spinal networks to threshold for fictive locomotion in combination with other protocols, and delineate the use of oxytocin to strengthen the efficiency of electrical stimulation to activate locomotor circuits

Functional Changes in Muscle Afferent Neurones in an Osteoarthritis Model: Implications for Impaired Proprioceptive Performance

Impaired proprioceptive performance is a significant clinical issue for many who suffer osteoarthritis (OA) and is a risk factor for falls and other liabilities. This study was designed to evaluate weight-bearing distribution in a rat model of OA and to determine whether changes also occur in muscle afferent neurones.Intracellular recordings were made in functionally identified dorsal root ganglion neurones in acute electrophysiological experiments on the anaesthetized animal following measurements of hind limb weight bearing in the incapacitance test. OA rats but not naïve control rats stood with less weight on the ipsilateral hind leg (P = 0.02). In the acute electrophysiological experiments that followed weight bearing measurements, action potentials (AP) elicited by electrical stimulation of the dorsal roots differed in OA rats, including longer AP duration (P = 0.006), slower rise time (P = 0.001) and slower maximum rising rate (P = 0.03). Depolarizing intracellular current injection elicited more APs in models than in naïve muscle afferent neurones (P = 0.01) indicating greater excitability. Axonal conduction velocity in model animals was slower (P = 0.04).The present study demonstrates changes in hind limb stance accompanied by changes in the functional properties of muscle afferent neurones in this derangement model of OA. This may provide a possible avenue to explore mechanisms underlying the impaired proprioceptive performance and perhaps other sensory disorders in people with OA

The gender specific frequency of risk factor and CHD diagnoses prior to incident MI: A community study

BACKGROUND: CHD is a chronic disease often present years prior to incident AMI. Earlier recognition of CHD may be associated with higher levels of recognition and treatment of CHD risk factors that may delay incident AMI. To assess timing of CHD and CHD risk factor diagnoses prior to incident AMI. METHODS: This is a 10-year population based medical record review study that included all medical care providers in Olmsted County, Minnesota for all women and a sample of men residing in Olmsted County, MN with confirmed incident AMI between 1995 and 2000. RESULTS: All medical care for the 10 years prior to incident AMI was reviewed for 150 women and 148 men (38% sample) in Olmsted County, MN. On average, women were older than men at the time of incident AMI (74.7 versus 65.9 years, p < 0.0001). 30.4% of the men and 52.0% of the women received diagnoses of CHD prior to incident AMI (p = 0.0002). Unrecognized and untreated CHD risk factors were present in both men (45% of men 5 years prior to AMI) and women (22% of women 5 years prior to first AMI), more common in men and those without a diagnosis of CHD prior to incident AMI (p < 0.0001). CONCLUSION: A CHD diagnosis prior to incident AMI is associated with higher rates of recognition and treatment of CHD risk factors suggesting that diagnosing CHD prior to AMI enhances opportunities to lower the risk of future CHD events

Neuroarchitecture of Aminergic Systems in the Larval Ventral Ganglion of Drosophila melanogaster

Biogenic amines are important signaling molecules in the central nervous system of both vertebrates and invertebrates. In the fruit fly Drosophila melanogaster, biogenic amines take part in the regulation of various vital physiological processes such as feeding, learning/memory, locomotion, sexual behavior, and sleep/arousal. Consequently, several morphological studies have analyzed the distribution of aminergic neurons in the CNS. Previous descriptions, however, did not determine the exact spatial location of aminergic neurite arborizations within the neuropil. The release sites and pre-/postsynaptic compartments of aminergic neurons also remained largely unidentified. We here used gal4-driven marker gene expression and immunocytochemistry to map presumed serotonergic (5-HT), dopaminergic, and tyraminergic/octopaminergic neurons in the thoracic and abdominal neuromeres of the Drosophila larval ventral ganglion relying on Fasciclin2-immunoreactive tracts as three-dimensional landmarks. With tyrosine hydroxylase- (TH) or tyrosine decarboxylase 2 (TDC2)-specific gal4-drivers, we also analyzed the distribution of ectopically expressed neuronal compartment markers in presumptive dopaminergic TH and tyraminergic/octopaminergic TDC2 neurons, respectively. Our results suggest that thoracic and abdominal 5-HT and TH neurons are exclusively interneurons whereas most TDC2 neurons are efferent. 5-HT and TH neurons are ideally positioned to integrate sensory information and to modulate neuronal transmission within the ventral ganglion, while most TDC2 neurons appear to act peripherally. In contrast to 5-HT neurons, TH and TDC2 neurons each comprise morphologically different neuron subsets with separated in- and output compartments in specific neuropil regions. The three-dimensional mapping of aminergic neurons now facilitates the identification of neuronal network contacts and co-localized signaling molecules, as exemplified for DOPA decarboxylase-synthesizing neurons that co-express crustacean cardioactive peptide and myoinhibiting peptides

Human neuronal excitation/inhibition balance explains and predicts neurostimulation induced learning benefits

Previous research has highlighted the role of the excitation/inhibition (E/I) ratio for typical and atypical development, mental health, cognition, and learning. Other research has highlighted the benefits of high-frequency transcranial random noise stimulation (tRNS)—an excitatory form of neurostimulation—on learning. We examined the E/I as a potential mechanism and studied whether tRNS effect on learning depends on E/I as measured by the aperiodic exponent as its putative marker. In addition to manipulating E/I using tRNS, we also manipulated the level of learning (learning/overlearning) that has been shown to influence E/I. Participants (n = 102) received either sham stimulation or 20-minute tRNS over the dorsolateral prefrontal cortex (DLPFC) during a mathematical learning task. We showed that tRNS increased E/I, as reflected by the aperiodic exponent, and that lower E/I predicted greater benefit from tRNS specifically for the learning task. In contrast to previous magnetic resonance spectroscopy (MRS)-based E/I studies, we found no effect of the level of learning on E/I. A further analysis using a different data set suggest that both measures of E/I (EEG versus MRS) may reflect, at least partly, different biological mechanisms. Our results highlight the role of E/I as a marker for neurostimulation efficacy and learning. This mechanistic understanding provides better opportunities for augmented learning and personalized interventions

AQUAMAN: a web-based decision support system for irrigation scheduling in peanuts

Peanut (Arachis hypogaea L.) is an economically important legume crop in irrigated production areas of northern Australia. Although the potential pod yield of the crop in these areas is about 8 t ha, most growers generally obtain around 5 t ha, partly due to poor irrigation management. Better information and tools that are easy to use, accurate, and cost-effective are therefore needed to help local peanut growers improve irrigation management. This paper introduces a new web-based decision support system called AQUAMAN that was developed to assist Australian peanut growers schedule irrigations. It simulates the timing and depth of future irrigations by combining procedures from the food and agriculture organization (FAO) guidelines for irrigation scheduling (FAO-56) with those of the agricultural production systems simulator (APSIM) modeling framework. Here, we present a description of AQUAMAN and results of a series of activities (i. e., extension activities, case studies, and a survey) that were conducted to assess its level of acceptance among Australian peanut growers, obtain feedback for future improvements, and evaluate its performance. Application of the tool for scheduling irrigations of commercial peanut farms since its release in 2004-2005 has shown good acceptance by local peanuts growers and potential for significantly improving yield. Limited comparison with the farmer practice of matching the pan evaporation demand during rain-free periods in 2006-2007 and 2008-2009 suggested that AQUAMAN enabled irrigation water savings of up to 50% and the realization of enhanced water and irrigation use efficiencies