Optical Control of Metabotropic Glutamate Receptors

G-protein coupled receptors (GPCRs), the largest family of membrane signaling proteins, respond to neurotransmitters, hormones and small environmental molecules. The neuronal function of many GPCRs has been difficult to resolve because of an inability to gate them with subtype-specificity, spatial precision, speed and reversibility. To address this, we developed an approach for opto-chemical engineering native GPCRs. We applied this to the metabotropic glutamate receptors (mGluRs) to generate light-agonized and light-antagonized “LimGluRs”. The light-agonized “LimGluR2”, on which we focused, is fast, bistable, and supports multiple rounds of on/off switching. Light gates two of the primary neuronal functions of mGluR2: suppression of excitability and inhibition of neurotransmitter release. The light-antagonized “LimGluR2block” can be used to manipulate negative feedback of synaptically released glutamate on transmitter release. We generalize the optical control to two additional family members: mGluR3 and 6. The system works in rodent brain slice and in zebrafish in vivo, where we find that mGluR2 modulates the threshold for escape behavior. These light-gated mGluRs pave the way for determining the roles of mGluRs in synaptic plasticity, memory and disease

A Guide To The Scrolls : Nottingham Studies on the Qumran Discoveries

London128 p.; 19 c

Effect of 3 weeks of detraining on the resting metabolic rate and body composition of trained males

ObjectiveTo examine the hypothesis that detraining decreases the resting metabolic rate (RMR) of long-term exercisers.DesignEight pairs of subjects were matched for age, mass and training volume. They were then randomly allocated to either a control group (continue normal training) or detraining group (stop normal training but continue activities of daily living).SettingExercise Physiology Laboratory, The Flinders University of South Australia.SubjectsSixteen male subjects (age 23.1 +/- 4.7 y (s.d.); mass 73.73 +/- 8.9 kg; VO2max 60.2 +/- 6.3 ml. kg-1.min-1; height 180.3 +/- 5.0 cm; body fat 14.6 +/- 5.4%) were selected from a pool of respondents to our advertisements.InterventionsEach pair of subjects was measured before and after a 3-week experimental period.ResultsTwo (groups) x 3 (2-, 3-and 4-compartment body composition models) ANOVAs were conducted on the difference between the pre- and post-treatment scores for percentage body fat, fat-free mass (FFM) and relative RMR (kJ.kg FFM-1.h-1). No significant between-group differences were identified except for the detraining group's small decrease in FFM (0.7 kg, P = 0.05). The main effects for body composition model were all significant; but the overall differences between the multicompartment models and the 2-compartment one were less than their technical errors of measurement. No significant interaction (P = 0.51) resulted from a 2 x 2 ANOVA on the pre- and post-treatment absolute RMR data for the control (315.2 and 311.9 kJ/h) and detraining groups (325.4 and 325.5 kJ/h).Conclusions3-weeks detraining is not associated with a decrease in RMR (kJ/h, kJ.kg FFM-1.h-1) in trained males; hence, our data do not support a potentiation of the RMR via exercise training. The greater sensitivity of the multicompartment models to detect changes in body composition was of marginal value