EFFECTS OF AN OBESOGENIC DIET ON EXCITATORY SYNAPTIC PLASTICITY IN THE NUCLEUS ACCUMBENS

Obesity is a public health issue worldwide, driven in part by the consumption of calorie-dense, palatable foods. In obesity-prone rats, a history of eating a ‘junk-food’ (JF) diet increases calcium-permeable AMPA receptor (CP-AMPAR) transmission in NAc medium spiny neurons (MSNs), and blockade of NAc CP-AMPARs is sufficient to reduce food-seeking. However, it is unclear whether NAc CP-AMPAR enhancements result in increased responsivity to excitatory drive (as CP-AMPARs are not uniformly added to all synapses), and/or alterations in subsequent NAc plasticity. Therefore, here adult male obesity-prone rats were given access to JF of chow and then whole-cell patch clamping was used to measure the effects of JF on membrane depolarization in response to increasing electrical stimulation of the slice and the expression of long-term potentiation (LTP) or long-term depression (LTD). LTP and LTD were elicited by pairing action potentials (APs) with excitatory post-synaptic potentials (eEPSPs). We found that JF enhanced MSN responsivity to excitatory drive, with larger changes in eEPSP amplitude across current injection and a reduction in stimulus intensity needed to trigger an action potential in JF vs chow groups. In addition, blockade of CP-AMPARs produced larger reductions in eEPSP amplitude in JF vs chow groups, consistent with a role for CP-AMPARs in JF-induced enhancements in responsivity to excitatory inputs. Initial plasticity results suggest that JF may also enhance LTP induction compared to controls. These findings indicate that JF-induced enhancements in NAc CP-AMPARs potentiate subsequent NAc plasticity in ways that may promote food-seeking and ultimately eating.