Subacute melamine exposure disrupts task-based hippocampal information flow via inhibiting the subunits 2 and 3 of AMPA glutamate receptors expression

Abstract

Although melamine exposure induces cognitive deficits and dysfunctional neurotransmission in hippocampal Cornus Ammonis (CA) 1 region of rats, it is unclear whether the neural function, such as neural oscillations between hippocampal CA3–CA1 pathway and postsynaptic receptors involves in these effects. The levels of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) subunit glutamate receptor (GluR) 1 and GluR2/3 in CA1 region of melamine-treated rats, which were intragastric treated with 300 mg/kg/day for 4 weeks, were detected. Following systemic or intra-hippocampal CA1 injection with GluR2/3 agonist, spatial learning of melamine-treated rats was assessed in Morris water maze (MWM) task. Local field potentials were recorded in CA3–CA1 pathway before and during behavioral test. General Partial Directed Coherence approach was applied to determine directionality of neural information flow between CA3 and CA1 regions. Results showed that melamine exposure reduced GluR2/3 but not GluR1 level and systemic or intra-hippocampal CA1 injection with GluR2/3 agonist effectively mitigated the learning deficits. Phase synchronization between CA3 and CA1 regions were significantly diminished in delta, theta and alpha oscillations. Coupling directional index and strength of CA3 driving CA1 were marked reduced as well. Intra-hippocampal CA1 infusion with GluR2/3 agonist significantly enhanced the phase locked value and reversed the melamine-induced reduction in the neural information flow (NIF) from CA3 to CA1 region. These findings support that melamine exposure decrease the expression of GluR2/3 subunit involved in weakening directionality index of NIF, and thereby induced spatial learning deficits.