Disruption of the direct perforant path input to the CA1 subregion of the dorsal hippocampus interferes with spatial working memory and novelty detection

Subregional analyses of the hippocampus suggest CA1-dependent memory processes rely heavily upon interactions between the CA1 subregion and entorhinal cortex. There is evidence that the direct perforant path (pp) projection to CA1 is selectively modulated by dopamine while having little to no effect on the Schaffer collateral (SC) projection to CA1. The current study takes advantage of this pharmacological dissociation to demonstrate that local infusion of the non-selective dopamine agonist, apomorphine (10, 15 mu g), into the CA1 subregion of awake animals produces impairments in working memory at intermediate (5 min), but not short-term (10 s) delays within a delayed non-match-to-place task on a radial arm maze. Sustained impairments were also found in a novel context with similar object-space relationships. Infusion of apomorphine into CA1 is also shown here to produce deficits in spatial, but not non-spatial novelty detection within an object exploration paradigm. In contrast, apomorphine produces no behavioral deficits when infused into the CA3 subregion or overlying cortex. These behavioral studies are supported by previous electrophysiological data that demonstrate local infusion of the same doses of apomorphine significantly modifies evoked responses in the distal dendrites of CA1 following angular bundle stimulation, but produces no significant effects in the proximal dendritic layer following stimulation of the SC. These results support a modulatory role for dopamine in EC-CA1, but not CA3-CA1 circuitry, and suggest the possibility of a fundamental role for EC-CA1 synaptic transmission in terms of detection of spatial novelty, and intermediate-term, but not short-term spatial working memory or object-novelty detection. (C) 2008 Elsevier B.V. All rights reserved.