Neurocomputing 44–46 (2002) 13–18 www.elsevier.com/locate/neucom Sensitivity to interstimulus interval due to calcium interactions in the Purkinje cell spines Jeanette Hellgren Kotaleski ∗ , Kim T. Blackwell George Mason University, Krasnow Institute, MS 2A1, Fairfax, VA 22030-4444, USA Abstract Pairing specic LTD (PSD) is produced by paired parallel ber (PF) and climbing ber (CF) stimulation and requires Ca 2+ elevation. CF or PF activation cause Ca 2+ increase through voltage dependent channels and IP3 induced Ca 2+ release, respectively. We developed a model of Ca 2+ dynamics in Purkinje cell spines to investigate why paired PF–CF activation is necessary for PSD. Simulations show a supralinear increase of the Ca 2+ signal if the CF input occurs in a restricted time interval following the PF input. Ca 2+ buers signicantly contribute to this phenomenon. This mechanism may be involved in the requirement of temporal specicity in classical conditioning. c  2002 Published by Elsevier Science B.V. Keywords: Classical conditioning; Purkinje cells; IP3 induced Ca 2+ release; Ca 2+ buers; LTD 1. Introduction In classical conditioning, memory storage depends on the order as well as the timing of the conditioned and unconditioned stimuli. A commonly used experimental paradigm is conditioning of the rabbit nictitating membrane response [3]. A tone is used as the conditioned stimulus and an air pu to the eyes as the unconditioned stimulus. The cerebellum, which is crucial to memory storage, receives information about the tone from parallel bres (PF) and receives information about the airpu from climbing bres (CF). Both PF and CF stimulation lead to Ca 2+ increases in the Purkinje cell spines and dendrites, the former through inositol trisphosphate (IP3) induced Ca 2+ release (IICR) while CF activation causes dendritic Ca 2+ spikes. * Corresponding author. Tel.: +1-703-993-4381; fax: +1-703-993-4325. E-mail addresses: jhallgre@mind.krasnow.gmu.edu (J. Hellgren Kotaleski), avrama@gmu.edu (K.T. Blackwell). 0925-2312/02/$-see front matter c  2002 Published by Elsevier Science B.V. PII:S0925-2312(02)00361-2