DISTINCT MECHANISMS OF CB1 AND GABAB RECEPTOR PRESYNAPTIC MODULATION OF STRIATAL INDIRECT PATHWAY PROJECTIONS TO MOUSE GLOBUS PALLIDUS
Presynaptic modulation is a fundamental process regulating synaptic transmission. Striatal indirect pathway projections originate from A2A-expressing spiny projection neurons (iSPNs), targeting the globus pallidus external segment (GPe) and control the firing of the tonically active GPe neurons via GABA release. It is unclear if and how the presynaptic G-protein-coupled receptors (GPCRs), GABAB and CB1 receptors modulate iSPN-GPe projections. Here we used an optogenetic platform to study presynaptic Ca2+ and GABAergic transmission at iSPN projections, using a genetic strategy to express the calcium sensor GCaMP6f or the excitatory channelrhodopsin (hChR2) on iSPNs. We found that P/Q-type calcium channels are the primary voltage-gated Ca2+ channel (VGCC) subtype controlling presynaptic calcium and GABA release at iSPN-GPe projections. N-type and L-type VGCCs also contribute to GABA release at iSPN-GPe synapses. GABAB receptor activation resulted in a reversible inhibition of presynaptic Ca2+ transients (PreCaTs) and an inhibition of GABAergic transmission at iSPN-GPe synapses. CB1 receptor activation did not inhibit PreCaTs but inhibited GABAergic transmission at iSPN-GPe projections. CB1 effects on GABAergic transmission persisted in experiments where NaV and KV1 were blocked, indicating a VGCC- and KV1-independent presynaptic mechanism of action of CB1 receptors. Taken together, presynaptic modulation of iSPN-GPe projections by CB1 and GABAB receptors is mediated by distinct mechanisms.
DEVELOPMENT OF EIGHT WIRELESS AUTOMATED CAGES SYSTEM WITH TWO LICK-O-METERS EACH FOR RODENTS.
Drinking behavior has been used in basic research to study metabolism, motivation, decision-making and different aspects of health problems, such as anhedonia and alcohol use disorders. In the majority of studies, liquid intake is measured by weighing the bottles before and after the experiment. This method does not tell much about the drinking microstructure, e.g., licking bouts and periods of preference for each liquid, which could be valuable to understand drinking behavior. To improve the data acquisition of drinking microstructure, companies have developed lick-o-meters devices that acquire timestamps when animals approach or drink from a specific sipper. Nevertheless, commercially available devices have elevated costs. Here, we present a low-cost alternative for a lick-o-meter system that allows wireless data acquisition of licking from eight cages with two sippers each. We run a three-phase validation protocol to ensure 1) proper choice of the sensor to detect licks; 2) adaptation of the device to a wireless transmission and realistic in silico tests; and 3) in vivo tests to correlate the amount of licks measured by the prototype and the bottle weight. The capacitive sensor presented appropriate recall and precision for our device. After adaptation to wireless transmission, the in silico validation demonstrated low reading and transmission errors for the device even when tested in extreme simultaneous licking conditions. Finally, a positive correlation between volume consumption and lick’s count in the in vivo test was observed, showing that the prototype can be used for in vivo studies interested in rodent drinking microstructure.
FOOD COMPOSITION CAN INFLUENCE HOW MUCH ALCOHOL YOUR ANIMAL MODEL DRINKS: A MINI-REVIEW ABOUT THE ROLE OF ISOFLAVONES
Standard laboratory diets have similar concentrations of proteins, carbohydrates and fat, but the concentration of some micronutrients can vary considerably. For example, the concentration of isoflavones can vary between 20 mg and 600 mg per gram of diet. Exposure to different concentrations of isoflavones interacts with alcohol intake, thereby influencing the results of alcohol research. In this mini-review, we describe correlations between isoflavone concentrations and alcohol intake based on data from previously published work. Although the administration of low doses of isoflavones can decrease alcohol intake in rats, there is a positive correlation between the isoflavone content in diets and alcohol intake in mice. This interaction seems to depend on the dose, route of administration, and time of exposure to isoflavones and may be related to specific neurobiological mechanisms. The literature also indicates that isoflavones can interact with some of alcohol's molecular targets and with neural pathways crucial to the alcohol reward process. Given these findings, more attention should be given to the different types of laboratory diets used in alcohol studies to allow better comparison and replication of animal research.