418 Computational Modeling of Entorhinal Cortex MICHAEL E. HASSELMO, a,d ERIK FRANSEN, b,e CLAYTON DICKSON, c,f AND ANGEL A. ALONSO c,f a Department of Psychology, Boston University, Boston, Massachusetts 02215, USA b Department of Numerical Analysis and Computing Science, Royal Institute of Technology, Stockholm, Sweden c Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada ABSTRACT: Computational modeling provides a means for linking the physio- logical and anatomical characteristics of entorhinal cortex at a cellular level to the functional role of this region in behavior. We have developed detailed sim- ulations of entorhinal cortical neurons and networks, with an emphasis on the role of acetylcholine in entorhinal cortical function. Computational modeling suggests that when acetylcholine levels are high, this sets appropriate dynamics for the storage of stimuli during performance of delayed matching tasks. In particular, acetylcholine activates a calcium-sensitive nonspecific cation cur- rent which provides an intrinsic cellular mechanism which could maintain neu- ronal activity across a delay period. Simulations demonstrate how this phenomena could underlie entorhinal cortex delay activity as described in pre- vious unit recordings. 191,164 Acetylcholine also induces theta rhythm oscilla- tions which may be appropriate for timing of afferent input to be encoded in hippocampus and for extraction of individual stored sequences from multiple stored sequences. Lower levels of acetylcholine may allow sharp wave dynam- ics which can reactivate associations encoded in hippocampus and drive the formation of additional traces in hippocampus and entorhinal cortex during consolidation. INTRODUCTION Experimental data about the parahippocampal region is available on a number of different levels, including detailed anatomical descriptions, 23,24,127 physiological characterization of intrinsic properties using entorhinal slice preparations, 96–98,39 correlations between unit spiking activity and behavior, 191,164 and lesion effects in rats and primates. 117,126 Computational modeling provides a means for bridging across these different levels of experimental analysis, for linking data at a physiolog- ical and anatomical level to the possible functional role of the parahippocampal region. We have been developing detailed compartmental simulations of entorhinal cor- tical neurons based on data obtained from the Alonso laboratory. Initially, we have d Address for correspondence: Dr. Michael E. Hasselmo, Dept. of Psychology, Boston University, 64 Cummington St., Boston, MA 02215. Tel.: (617) 353-1397; fax: (617) 353-1424. e-mail: hasselmo@berg.bu.edu e e-mail: erikf@sans.kth.se f e-mail: mdao@musica.mcgill.ca