NEUROBIOLOGY OF LEARNING AND MEMORY 70, 101–112 (1998) ARTICLE NO. NL983841 Information Processing with Frequency- Dependent Synaptic Connections Henry Markram, Anirudh Gupta, Asher Uziel, Yun Wang, and Misha Tsodyks Department of Neurobiology, The Weizmann Institute for Science, Rehovot, 76100, Israel The efficacy of synaptic transmission between two neurons changes as a function of the history of previous activations of the synaptic connection. This history dependence can be characterized by examining the dependence of transmission on the frequency of stimulation. In this framework synaptic plasticity can also be examined in terms of changes in the frequency dependence of transmission and not merely in terms of synap- tic strength which constitutes only a linear scaling mechanism. Recent work shows that the frequency dependence of transmission determines the content of information transmitted between neurons and that synaptic modifications can change the content of information transmitted. Multipatch-clamp recordings revealed that the frequency dependence of transmission is potentially unique for each synaptic connection made by a single axon and that the class of pre–postsynaptic neuron determines the class of frequency dependence (activity independent), while the unique activity relationship between any two neurons could determine the precise values of the parameters within a specific class (activity dependent). The content of information transmitted between neurons is also formalized to provide synaptic transfer functions which can be used to determine the role of the synaptic connection within a network of neurons. It is proposed that deriving synaptic transfer functions is crucial in order to understand the link between synaptic transmission and information processing within networks of neurons and to understand the link between synaptic plasticity and learning and memory.  1998 Academic Press INTRODUCTION Hebb’s formulation for the cellular substrates of learning and memory ap- pears to have been largely influenced by the seemingly logical need for stimu- lus-driven neural activity patterns to ‘‘reverberate’’ within the nervous system even after the stimulus is over, since this could account for short-term memory (Hebb, 1949; Amit, 1996). The ‘‘growth of the assembly’’ by specific modifica- tions of the efficiency of transmission between selected groups of neurons was then proposed to set up the conditions to reactivate these reverberations which could account for long-term memory storage. What Hebb and his followers did not consider were published data (Feng, 1941; Hutter, 1952; Liley & North, 1953; del Castillo and Katz, 1954; Liley, 1956; Takeuchi, 1958; Hubbard, 1963; This work was supported by grants from the ONR, Minerva, GIF, BSF, and the Wolfson, Grodet- sky, and Levine foundations to H.M. Address requests for reprints and correspondence to Henry Markram, Department of Neurobiol- ogy, The Weizmann Institute for Science, Rehovot, 76100, Israel. Fax: /972-89344131. E-mail: bnmark@weizmann.weizmann.ac.il. 101 1074-7427/98 $25.00 Copyright  1998 by Academic Press All rights of reproduction in any form reserved.