ARTICLE IN PRESS BRESR 100400 No of pages 13 4C B RA I N R E SE A R CH RE V IE W S X X 20 0 6 XX X XX X a v a i l a b l e a t w w w s c i e n c e d i r e c t c o m w w w e l s e v i e r c o m l o c a t e b r a i n r e s r e v Review Memory formation by neuronal synchronization Nikolai Axmacher a Florian Mormann a Guillen Fern ndez b Christian E Elger a Juergen Fell a a Department of Epileptology University of Bonn Sigmund Freud Str 25 53105 Bonn Germany F C Donders Centre for Cognitive Neuroimaging P O Box 9101 6500 HB Nijmegen The Netherlands b A R T I C LE I N FO AB S T R A C T Article history Cognitive functions not only depend on the localization of neural activity but also on Accepted 24 January 2006 the precise temporal pattern of activity in neural assemblies Synchronization of action potential discharges provides a link between large scale EEG recordings and cellular plasticity mechanisms Here we focus on the role of neuronal synchronization Keywords in different frequency domains for the subsequent stages of memory formation Declarative memory Recent EEG studies suggest that synchronized neural activity in the gamma Neuronal synchronization frequency range around 30 100 Hz plays a functional role for the formation of Gamma oscillation declarative Hippocampus synchronization between hippocampal and parahippocampal regions may induce Synaptic plasticity LTP in the CA3 region of the hippocampus In order to encode spatial locations or Phase synchronization sequences of multiple items and to guarantee a defined temporal order of memory long term memories in humans On the cellular level gamma processing synchronization in the gamma frequency range has to be accompanied by a stimulus locked phase reset of ongoing theta oscillations Simultaneous gammaand theta dependent plasticity leads to complex learning rules required for realistic declarative memory formation Subsequently consolidation of declarative memories may occur via replay of newly acquired patterns in so called sharp wave ripple complexes predominantly during slow wave sleep These irregular bursts induce longer lasting forms of synaptic plasticity in output regions of the hippocampus and in the neocortex In summary synchronization of neural assemblies in different frequency ranges induces specific forms of cellular plasticity during subsequent stages of memory formation 2006 Elsevier B V All rights reserved Contents 1 2 Introduction Gamma frequency hypothesis 2 1 Hippocampal gamma synchronization timing 2 2 Regional basis of rhinal hippocampal synchronization and spike 0 0 0 Corresponding author Fax 49 228 287 6294 E mail address nikolai axmacher ukb uni bonn de N Axmacher 0165 0173 see front matter 2006 Elsevier B V All rights reserved doi 10 1016 j brainresrev 2006 01 007 0 ARTICLE IN PRESS 2 B RA I N R E SE A RC H R E V IE W S X X 2 0 0 6 XX X XX X 2 3 Rhinal hippocampal gamma synchronization supports LTP in CA3 2 4 Unresolved issues 3 Theta gamma hypothesis 3 1 Theta phase dependent encoding 3 2 Theta activity and LTP 3 3 Theta gamma interaction 4 Memory consolidation by high frequency oscillations 4 1 Memory replay and consolidation 4 2 Memory consolidation via sharp wave ripple complexes 5 Conclusions Acknowledgment References 1 0 0 0 0 0 0 0 0 0 0 0 0 Introduction The basic unit of information processing in the human brain is an action potential Action potentials of individual neurons are not independent from each other but are correlated by synchronized activity in neuronal assemblies Because it has been shown in various systems that the exact spike times and not just the firing rate of individual neurons are a relevant measure of the activation of these neurons Rieke et al 1997 an increasing synchrony reduces the amount of information that the spike times of any individual neuron contains Thus synchronization in itself is unlikely to serve as a neuronal code Instead of representing time coded information on stimulus features it rather appears to support specific processes during neural communication Fries 2005 the behavioral specificity of synchronization phenomena e g in the gamma range between 30 and 100 Hz suggests a functional role of synchronized activity for neural information processing e g Ekstrom et al 2003 Furthermore changes in network oscillations during pathological states e g during epileptic seizures may impair normal brain function The mechanistic role of synchronized activity for information processing in single neurons is far from evident primarily the observation of synchronized activity in a given frequency band signifies just that neural activity is correlated There may be a variety of mechanisms by which a neural network is synchronized in a certain frequency range and each mechanism may have different effects For example theta oscillations 3 8 Hz have been described both during pathological states in the human EEG and during episodes of memory encoding in specific areas of the medial temporal lobe in animals e g Buzs ki 2002 In general an increasing synchrony may strengthen the impact of the synchronously firing neurons onto common target cells if these target cells integrate their inputs over small time scales Fries 2005 Furthermore if the synaptic connections between the synchronously firing neurons are modifiable by spike timingdependent plasticity an increasing synchronicity between these neurons may induce long term potentiation of these synapses As a result the stimulus properties that have activated these neurons are associated with each other to form a new memory In our article we attempt to give a detailed description of this process focusing on synchronous activity in the gamma and theta frequency range Accordingly two main functions have been proposed for the synchronization of gamma oscillations Many observations support the view that gamma synchronization binds participating neurons that represent attended as opposed to background features of a stimulus e g Fries et al 2001 Engel and Singer 2001 Fell et al 2003a According to this view precise synchronization in the gamma frequency range serves widely distributed networks of neurons to effectively activate common target cells Only recently a different though perhaps related function of gamma oscillation has been proposed formation of declarative memories i e long term storage of consciously accessible information into memory Fell et al 2001 Gruber et al 2004 Sederberg et al 2003 More specifically late induced gamma