A novel GPR55-mediated satiety signal in the oval Bed Nucleus of the Stria Terminalis

Abstract

Nestled within feeding circuits, the oval (ov) region of the Bed Nucleus of the Stria Terminalis (BNST) may be critical for monitoring energy balance through changes in synaptic strength. Here we report that bidirectional plasticity at ovBNST GABA synapses was tightly linked to the caloric state of male rats, seesawing between long-term potentiation (iLTP, fed) and depression (iLTD, food restricted). L-α-lysophosphatidylinositol (LPI) acting on GPR55 receptors and 2-arachidonoylglycerol (2-AG) through CB1R were respectively responsible for fed (iLTP) and food restricted (iLTD) states. Thus, we have characterized a potential gating mechanism within the ovBNST that may signal metabolic state within the rat brain feeding circuitry.

Amylin as a Future Obesity Treatment

“…1). 17,18 Chronically elevated doses of amylin fail to induce hypophagia in rats with lesions in the AP. 19 Similarly, when the amylin receptor antagonist AC 187 is infused directly into the AP of rats, food intake is increased.…”

Exo- and Endo-cannabinoids in Depressive and Suicidal Behaviors

“…Using reverse transcription polymerase chain reaction, CB2 receptor mRNA expression was found in cerebellum, cortex and brainstem of the rat brain (26). GPR55 is expressed in multiple brain regions, including PFC (prefrontal cortex), amygdala and striatum (27)(28)(29)(30), and is shown to dimerize with CB1 receptors in the striatum (31). Recent studies demonstrate that lysophosphotidyl inositol (LPI) and NAGly palmitoylethanolamide (PEA) elicit biological responses through GPR55 (18,19,32,33) suggesting that these two lipids are endogenous ligands for GPR55.…”

The Bed Nucleus of the Stria Terminalis, Homeostatic Satiety, and Compulsions: What Can We Learn From Polydipsia?

“…Indeed, we recently identified a neural mechanism within the ovBNST that may represent the homeostatic emotion of hunger-satiety (Figure 2; Hawken et al, 2019). In order to establish compulsive drinking through the SIP protocol, animals must first be hungry, a drive-state typically induced through food restriction (Figure 1).…”

“…In sated (fed ad libitum ) male rats, low-frequency stimulation of ovBNST GABAergic synapses produces increases in inhibitory postsynaptic currents and promotes long-term potentiation (iLTP) in the majority of neurons recorded. Following acute food-restriction (24 h), however, GABAergic plasticity toggles to long-term depression (iLTD) via endocannabinoid dependent mechanisms (Figure 2; Hawken et al, 2019). In this framework, the novel endocannabinoid receptor GPR55 and its ligand, LPI, mediate a hunger-satiety signal (iLTP) while the classic endocannabinoid CB1 receptors and their ligand, 2-AG, promote a hunger-state (iLTD).…”

“…Oval bed nucleus of the stria terminalis (ovBNST) inhibitory plasticity is satiety-state independent in SIP. Adapted with permission from Hawken et al (2019) and Gardner Gregory (2018). Plasticity at ovBNST GABAergic synapses is caloric-state dependent exhibiting bi-directional plasticity.…”