Sucrose Ingestion Induces Rapid AMPA Receptor Trafficking

Abstract

The mechanisms by which natural rewards such as sugar affect synaptic transmission and behavior are largely unexplored. Here, we investigate regulation of nucleus accumbens synapses by sucrose intake. Previous studies have shown that AMPA receptor trafficking is a major mechanism for regulating synaptic strength, and that in vitro, trafficking of AMPA receptors containing the GluA1 subunit takes place by a two-step mechanism involving extrasynaptic and then synaptic receptor transport. We report that in rat, repeated daily ingestion of a 25% sucrose solution transiently elevated spontaneous locomotion and potentiated accumbens core synapses through incorporation of Ca2+-permeable AMPA receptors (CPARs), which are GluA1-containing, GluA2-lacking AMPA receptors. Electrophysiological, biochemical and quantitative electron microscopy studies revealed that sucrose training (7 days) induced a stable (>24 hr) intraspinous GluA1 population, and that in these rats a single sucrose stimulus rapidly (5 min) but transiently (<24 hr) elevated GluA1 at extrasynaptic sites. CPARs and dopamine D1 receptors were required in vivo for elevated locomotion after sucrose ingestion. Significantly, a 7-day protocol of daily ingestion of a 3% solution of saccharin, a non-caloric sweetener, induced synaptic GluA1 similarly to 25% sucrose ingestion. These findings identify multi-step GluA1 trafficking, previously described in vitro, as a mechanism for acute regulation of synaptic transmission in vivo by a natural orosensory reward. Trafficking is stimulated by a chemosensory pathway that is not dependent on the caloric value of sucrose.

Incorporation of inwardly rectifying AMPA receptors at silent synapses during hippocampal long-term potentiation

“…Despite the accumulating evidence for a role of GluA2-lacking AMPA receptors in the expression of LTP in several brain regions [18,[25][26][27][28], there is controversy as to the role GluA2-lacking AMPA receptors play in the expression of hippocampal LTP. Two studies failed to find evidence for such a role forGluA2-lacking AMPA receptors [29,30]; however, two other studies do provide evidence for incorporation of GluA2-lacking AMPA receptors in LTP [31,32].…”

“…Since these early studies on the involvement of GluA2-lacking, calcium-permeable AMPA receptors in cerebellar and hippocampal synaptic plasticity, a number of studies have shown that similar mechanisms may underlie plasticity in other brain areas, including primary sensory cortex, ventral tegmental area (VTA), amygdala and hypothalamus [18,[25][26][27][28]. Despite this, considerable controversy remains for hippocampal CA1 LTP on the role of GluA2-lacking AMPA receptors.…”

Persistent neuropathic pain increases synaptic GluA1 subunit levels in core and shell subregions of the nucleus accumbens

“…These unique biophysical properties enable CPARs to play an important role at the synapse, including the induction of long-term potentiation (LTP) or long-term depression (LTD) [16, 27, 35]. By regulating synaptic strength, CPARs modulate a diverse set of behaviors [14, 15, 24, 34, 55, 56]. Our data raises the possibility of CPAR formation in both the core and shell subregions in pain states.…”

“…A number of studies have described GluA1 upregulation in the NAc after repeated or prolonged consumption of natural rewards or cocaine [45, 55]. In these studies, homeostatic plasticity has been posited as a possible mechanism for the increase in GluA1 subunits.…”

“…Dissections of core and shell were performed according to coordinates of the standard rat atlas. The NAc core was dissected using a circular micropunch of approximately 1mm radius centered at the anterior commissure, and areas medial and ventro-lateral to (immediately surrounding) the NAc core were collected as NAc shell under a dissecting microscope [37, 55]. Synaptosome fractions of core and shell were prepared as described previously [29, 46].…”