Fluctuations in successive waves of oscillatory neighborhood field potentials (LFPs) reflect the ongoing processing of neuron populations. but not GABA blockers abolished Schaffer LFPs when applied to the active but not passive subcellular domains of pyramidal cells. The known chemical nature of the oscillatory LFP allowed an empirical offset of the temporal component of Schaffer LFPs, such that following reconstruction they yield only sinks or sources at the appropriate sites. In terms of number and polarity, some waves increased and others decreased proportional to the concomitant inputs in native multisynaptic LFPs. Interestingly, the processing also retrieved the initiation time for each wave, which can be used to discriminate afferent from postsynaptic cells in standard spike-phase correlations. The applicability of this approach to other pathways and structures is usually discussed. Introduction Local field potentials (LFPs) are raised by populace synaptic currents and typically display irregular behavior interspersed with epochs of prominent oscillatory activity that are concentrated in narrow frequency bands [1]. Computationally, LFP-oscillations can be viewed as temporal windows to precisely control the timing of converging pathways. They may also have a role in the formation of neuron assemblies [2]. Notably, significant fluctuations in the amplitude, duration and spatial localization of successive LFP-waves are observed that reflect the rich internal dynamics of the afferent and target populations [3,4,5,6,7]. Timp3 In the monolayered hippocampus, the bulk of currents is usually generated by a single target populace [7,8,9,10], but there may be more in the cortex [11]. Reading amplitude fluctuations in LFP-waves requires an understanding of the number and nature of the synaptic pathway/s from which Ecdysone tyrosianse inhibitor they originate (i.e., single or multiple, excitatory or inhibitory). Classical ambiguities regarding the localization and synaptic nature of the current sources underlying LFPs impede a straightforward interpretation of these fluctuations [12]. Also, phase associations between LFP-wave Ecdysone tyrosianse inhibitor and spike trains, which are widely used in the literature to establish cause-effect relationships rarely allow one to determine whether the firing unit is usually pre- or postsynaptic to LFPs. Although the theoretical bases of LFP generation are well established [13,14,15,16,17,18,19], this topic is usually rarely explored directly due to the significant troubles in resolving the inverse problem of identifying the neuronal current sources from LFPs with subcellular precision. Indeed, the number of co-activated afferent populations at a given instant is usually unknown [7]. Moreover, most modern amplifiers reject the DC component of LFPs and as a result, defining the polarity of Ecdysone tyrosianse inhibitor the AC-coupled Ecdysone tyrosianse inhibitor LFP-oscillations is usually precluded by the lack of a baseline, which in turn frustrates the determination of the excitatory or inhibitory nature of the underlying synaptic currents. As a consequence, one cannot set a time reference for the initiation of each LFP-cycle, which is necessary to establish the phase of the ongoing fluctuations. In laminated brain structures with stratified inputs, such as the cortex and hippocampus, the polarity of underlying transmembrane currents can theoretically be estimated from the spatial gradients of the extracellular field potential [13] through current source-density (CSD) analysis [20,21]. CSD maps are free of volume-conducted currents from remote cell generators. Therefore, this analysis identifies membrane domains that produce a net flow of inward or outward currents (sinks and sources, respectively), which can then be matched to anatomical data to determine whether a given domain is usually associated with synaptic sites or with passive counterparts. While this approach is usually valid for customary evoked potentials during exogenous activation Ecdysone tyrosianse inhibitor of individual major pathways [11,20,22,23,24,25], it cannot be applied to ongoing LFPs. The CSD of oscillatory LFPs usually exhibits a temporal succession of sinks and sources in both the active and passive domains [5,26,27,28,29,30,31,32]. This provides no information as to the polarity.