Slide 1

Introduction The Temporoammonic (TA) projection from entorhinal cortex (EC) layer III to the s. l-m. layer of the CA1 subregion is the direct source of specific sensory information from converging cortical inputs to the hippocampus, supplying approximately 1/3 of the EC projections (in the rat) (Amaral, Ishizuka, & Claiborne, 1990). The CA1 subregion also receives afferent input from the CA3 subregion originating from layer II of EC and projecting via the trisynaptic loop to the dentate gyrus (DG) and CA3 subregions and on through the Schaffer collaterals (Sc). CA1 has previously been implicated in retrieval and mismatch/novelty detection operations for intermediate to long-term memory of spatial information (Lee & Kesner, 2003, 2004; Lee et al., 2005). Lesions of the trisynaptic circuitry and/or the Sc input to CA1 do not produce deficits in spatial selectivity of place cell activity, hence implicating the TA pathway in place cell representation in CA1 (Brun, Otnaess, Molden, Steffenach, & Witter, 2002; Brun, Leutgeb, Wu, Schwarcz, Witter, Moser & Moser, 2003; Vinogradova, 1984). It has been shown in vitro that dopamine applied to the hippocampal slice can selectively inhibit the TA pathway and modulate CA1 function (Otmakhova & Lisman, 1999). We propose that the 1) TA pathway to the CA1 region of the hippocampus is functionally important in CA1-specific memory tasks and 2) The TA pathway is modulated by the non-selective dopamine agonist, apomorphine. This series of experiments tested rats on two different CA1-sensitive tasks, specifically contextual fear conditioning, and a spatial/object novelty task. In order to reliably demonstrate that the deficits observed behaviorally can be attributed to the disruption of the direct TA pathway, a series of electrophysiological experiments were carried out in vivo. Conclusions The results indicate that apomorphine (10, 15 or 21 ug) infused into the CA1 region of the hippocampus a) disrupts detection of spatial novelty and b) retrieval of contextual fear similarly to CA1 lesions. Neither apomorphine nor CA1 lesions appeared to produce deficits in locomotor activity, detection of novel objects in a familiar spatial configuration, or retrieval of cue-associated fear To the extent that the pharmacological manipulations used in this series of experiments selectively disrupts the TA pathway, the results generally indicate that the TA pathway plays an important modulatory role in many forms of CA1- dependent mnemonic processing and has raised the possibility of a more fundamental role for entorhinal cortex (EC)CA1 synaptic transmission. Using in vivo electrophysiology, apomorphine (10, 15 ug) produced what appear to be significant changes in fEPSP as recorded in the CA1 distal dendrites after TA stimulation, while it appears to have no effect on fEPSP in the proximal dendritic layer of CA1 after Sc stimulation In Vivo Electrophysiology Spatial/Object Novelty Task Fear Conditioning Schaffer Collateral Stimulation Perforant Path Stimulation AN ELECTROPHYSIOLOGICAL AND BEHAVIORAL CHARACTERIZATION OF THE TEMPOROAMMONIC PATHWAY: DISRUPTION PRODUCES DEFICITS IN RETRIEVAL AND SPATIAL MISMATCH D.R. Vago, and R.P. Kesner. Dept. of Psychology, University of Utah, SLC, UT 84112 647.5 TA pathway 6 min Novel Object Intro D AB E C E AB D CE F B D C Session 24Session 7Session 56Session 1 3 min 6 min Familiarization 6 min Habituation 6 min Novel Spatial change 3 min Histology Control CA1 cannula CA1 lesion Baseline Post Apo (15 ug) 20 min 0.5 mv 5 ms