Copyright © 1997, Elsevier Science Ltd. All rights reserved. 0166 - 2236/97/$17.00 PII: S0166-2236(96)10075-8 TINS Vol. 20, No. 3, 1997 125 T O CARRY OUT any cognitive or motor task, be it memory formation or the execution of a move- ment, action potentials must occur in specific sets of neurons at the right time. To accomplish this, neurons of the CNS continuously evaluate their inputs, arriving in the form of ever-changing combinations of synaptic potentials, to determine if and when an action potential should be initiated. Fundamental to an understanding of this process of synaptic inte- gration is the knowledge of where within a neuron these synaptic inputs sum to initiate a neuron’s main output signal – the action potential. Work in the 1950s suggested that action potential initiation in neurons of the CNS occurs in the axon initial segment (for review, see Ref. 1), the unmyeli- nated region, which forms the beginning of the axon (Fig. 1). As the axon usually originates from the soma of these neurons, this site provides a natural focal point for summation of synaptic inputs from different locations in the dendritic tree. Over the years, how- ever, many studies have suggested that action poten- tials can also be initiated within dendrites 2–16 . This idea has gained appeal in recent years following evi- dence that the dendrites of many neurons in the CNS are electrically active (for review, see Ref. 17). This review summarizes recent findings pertaining to the debate concerning the site of action potential initi- ation in neurons of the mammalian CNS (Ref. 18), and describes how, once initiated, action potentials propagate within the dendritic tree. Axonal or dendritic action potential initiation: what is the difference? Action potentials are regenerative electrical events, usually mediated by voltage-activated Na + channels, which are initiated following depolarization of the membrane potential to a threshold level. During the normal functioning of the CNS this threshold is reached after temporal or spatial summation of synap- tic inputs made largely on to a neuron’s dendritic tree. The ability of a synaptic event to influence action potential initiation (its efficacy) will therefore depend on the location of the activated synapse in relation to the site of action potential initiation, and on how this synaptic event is shaped by the active and passive properties of the dendritic tree. If action potential in- itiation can occur only in the axon, and the dendritic tree behaves passively, the efficacy of each synaptic input will be related to its electrotonic distance from the axon 19 . Conversely, if action potentials can also be initiated in the dendrites, then local interactions in the den- dritic tree (both active and passive) will play a more important role. While such a neuron could have increased computational power, to utilize this would require tight control over the precise timing of acti- vation of synaptic inputs to particular parts of the dendritic tree 20 . In addition, to transfer fully the infor- mation contained within a dendritic action potential to other neurons, dendritic action potentials would need to propagate reliably from their site of initiation to the axon – normally the sole output pathway for action potentials in neurons. This would require dendritic voltage-activated Na + (or Ca 2+ ) channels at densities sufficient to support both the initiation and propagation of dendritic action potentials to the axon. A consequence of such an arrangement would be that once threshold for an action potential is reached somewhere in the neuron no more integration in the neuron would be possible, as this action potential would propagate everywhere, resetting the membrane potential over the entire dendritic tree. Furthermore, the information contained in action potentials initiated in distal parts of the dendritic tree would sometimes G. Stuart et al. – Initiation and spread of action potentials R EVIEW Action potential initiation and backpropagation in neurons of the mammalian CNS Greg Stuart, Nelson Spruston, Bert Sakmann and Michael Häusser Most neurons in the mammalian CNS encode and transmit information via action potentials. Knowledge of where these electrical events are initiated and how they propagate within neurons is therefore fundamental to an understanding of neuronal function.While work from the 1950s suggested that action potentials are initiated in the axon, many subsequent investigations have suggested that action potentials can also be initiated in the dendrites. Recently,experiments using simultaneous patch-pipette recordings from different locations on the same neuron have been used to address this issue directly.These studies show that the site of action potential initiation is in the axon,even when synaptic activation is powerful enough to elicit dendritic electrogenesis. Furthermore, these and other studies also show that following initiation, action potentials actively backpropagate into the dendrites of many neuronal types,providing a retrograde signal of neuronal output to the dendritic tree. Trends Neurosci. (1997) 20, 125–131 Greg Stuart is at the Division of Neuroscience, John Curtin School of Medical Research, Australian National University, Canberra, ACT 0200, Australia. Nelson Spruston is at the Dept of Neurobiology and Physiology, Institute for Neuroscience, Northwestern University, Evanston, IL 60208-3520, USA. Bert Sakmann is at Abteilung Zellphysiologie, Max-Planck- Institut für medizinische Forschung, Jahnstr. 29, 69120 Heidelberg, Germany. Michael Häusser is at the Laboratoire de Neurobiologie, Ecole Normale Supérieure, 46 rue d’Ulm, 75005 Paris, France.