EFFECTS OF MEMANTINE ON EXPERIENCE-DEPENDENT PLACE FIELD EXPANSION IN AGED RATS

S.N. Burke *; A.P. Maurer; N. Insel; Z. Navratilova; B.L. McNaughton; G.L. Wenk; C.A. Barnes

NSMA , Univ Arizona, Tucson, AZ, USA

Neural network models dating back to Hebb's (1949) concept of the 'phase sequence' of cell assemblies have suggested that an associative, temporally asymmetric synaptic plasticity mechanism could serve to encode sequences or episodes of experience. In agreement with theories of sequence learning, hippocampal place fields in CA1 of young rats expand asymmetrically during repeated route following resulting in a shift in the center of mass of place fields in the direction opposite to the rat’s trajectory (Mehta et al., 1997). The magnitude of this place field expansion, however, significantly decreases in aged rats (Shen et al., 1997) and does not occur when young rats are administered the NMDA receptor antagonist CPP (Ekstrom et al., 2001). These data suggest that functional alterations in the NMDA receptors of aged rats could result in neural plasticity and spatial learning deficits. Consistent with this hypothesis are observations that aged rats show deficits in LTP induction and maintenance that may be partially explained by an increase in Ca 2+ conductances. The low affinity NDMA antagonist memantine has been shown to increase the maintenance of LTP (Barnes et al., 1996) and is now in therapeutic use for Alzheimer’s disease. In aged rats memantine may act to reduce the amount of Ca 2+ that enters the neuron during NMDA receptor activation thereby improving plasticity. The current investigation recorded CA1 place cells as aged rats traversed a circular track to examine the effects of memantine on this experience-dependent place field plasticity phenomenon. Aged rats were acutely administered either 10mg/kg or 15mg/kg of memantine intraperitoneally 20 minutes prior to the episode of track-running and the shift in place field center of mass was measured across laps. Preliminary data show that compared to the saline baseline condition, acute administration of memantine lead to at least partial reinstatement of place field expansion plasticity in aged rats.

Support Contributed By: AG012609 & AG010546

Key words: CA1, NMDA receptor, plasticity, Alzheimer’s Disease