Ongoing network activity often manifests as irregular fluctuations in local field potentials (LFPs), a complex mixture of multicellular synaptic currents of varying locations and extensions. Among other conditions, for synchronously firing presynaptic units to generate sizable postsynaptic LFPs, their axonal territories should overlap. We have taken advantage of anatomical regularity of the rat hippocampus and combined multiple linear recordings and spatial discrimination techniques to separate pathway-specific LFPs with enough spatial resolution to discriminate postsynaptic regions of varying activation, and to investigate their presynaptic origin, chemical nature, and spatial extension. We identified 6 main excitatory and inhibitory LFP generators with different synaptic territories in principal cells and hippocampal subfields matching anatomical pathways. Some recognized pathways did not contribute notably to LFPs. Each showed different septo-temporal spatial modules over which the field potential fluctuations were synchronous. These modules were explained by either the strong overlap of synaptic territories of coactivated afferent neurons (e.g., CA3 clusters for CA1 Schaffer LFPs), or widespread coalescence of postsynaptic territories (granule cell somatic inhibition). We also show evidence that distinct modes of afferent synchronization generate stereotyped spatial patterns of synchronous LFPs in one pathway. Thus, studying spatial coherence of pathway-specific LFPs provides remote access to the dynamics of afferent populations.

Information processing and exchange between brain nuclei are made through spike series sent by individual neurons in highly irregular temporal patterns. Synchronization in cell assemblies, proposed as a network language for internal neural representations, still has little experimental support. We use a novel technique to extract pathway-specific local field potentials (LFPs) in the hippocampus to explore the ongoing temporal structure of a single presynaptic input, the CA3 Schaffer pathway, and its contribution to the spontaneous output of CA1 units in anesthetized rat. We found that Schaffer-specific LFPs are composed of a regular succession of pulse-like excitatory packages initiated by spontaneous clustered firing of CA3 pyramidal cells to which individual units contribute variably. A fraction of these packages readily induce firing of CA1 pyramidal cells and interneurons, the so-called Schaffer-driven spikes, revealing the presynaptic origin in the output code of single CA1 units. The output of 70% of CA1 pyramidal neurons contains up to 10% of such spikes. Our results suggest a hierarchical internal operation of the CA3 region based on sequential oscillatory activation of pyramidal cell assemblies whose activity partly gets in the output code at the next station. We conclude that CA1 output may directly reflect the activity of specific ensembles of CA3 neurons. Thus, the fine temporal structure of pathway-specific LFPs, as an accurate readout of the activity of a presynaptic population, is useful in searching for hidden presynaptic code in irregular spikes series of individual neurons and assemblies.

Local field potentials (LFPs) capture the electrical activity produced by principal cells during integration of converging synaptic inputs from multiple neuronal populations. However, since synaptic currents mix in the extracellular volume, LFPs have complex spatiotemporal structure, making them hard to exploit. Here we propose a biophysical framework to identify and separate LFP-generators. First we use a computational multineuronal model that scales up single cell electrogenesis driven by several synaptic inputs to realistic aggregate LFPs. This approach relies on the fixed but distinct locations of synaptic inputs from different presynaptic populations targeting a laminated brain structure. Thus the LFPs are contributed by several pathway-specific LFP-generators, whose electrical activity is defined by the spatial distribution of synaptic terminals and the time course of synaptic currents initiated in target cells by the corresponding presynaptic population. Then we explore the efficacy of independent component analysis to blindly separate converging sources and reconstruct pathway-specific LFP-generators. This approach can optimally locate synaptic inputs with subcellular accuracy while the reconstructed time course of pathway-specific LFP-generators is reliable in the millisecond scale. We also describe few cases where the non-linear intracellular interaction of strongly overlapping LFP-generators may lead to a significant cross-contamination and the appearance of derivative generators. We show that the approach reliably disentangle ongoing LFPs in the hippocampus into contribution of several LFP-generators. We were able to readout in parallel the pathway-specific presynaptic activity of projection cells in the entorhinal cortex and pyramidal cells in the ipsilateral and contralateral CA3. Thus we provide formal mathematical and experimental support for parallel readout of the activity of converging presynaptic populations in working neuronal circuits from common LFPs.

The activity of mitral and tufted cells, the principal neurons of the olfactory bulb, is modulated by several classes of interneurons. Among them, diverse periglomerular (PG) cell types interact with the apical dendrites of mitral and tufted cells inside glomeruli at the first stage of olfactory processing. We used paired recording in olfactory bulb slices and two-photon targeted patch-clamp recording in vivo to characterize the properties and connections of a genetically identified population of PG cells expressing enhanced yellow fluorescent protein (EYFP) under the control of the Kv3.1 potassium channel promoter. Kv3.1-EYFP ϩ PG cells are axonless and monoglomerular neurons that constitute ϳ30% of all PG cells and include calbindin-expressing neurons. They respond to an olfactory nerve stimulation with a short barrage of excitatory inputs mediated by mitral, tufted, and external tufted cells, and, in turn, they indiscriminately release GABA onto principal neurons. They are activated by even the weakest olfactory nerve input or by the discharge of a single principal neuron in slices and at each respiration cycle in anesthetized mice. They participate in a fast-onset intraglomerular lateral inhibition between principal neurons from the same glomerulus, a circuit that reduces the firing rate and promotes spike timing variability in mitral cells. Recordings in other PG cell subtypes suggest that this pathway predominates in generating glomerular inhibition. Intraglomerular lateral inhibition may play a key role in olfactory processing by reducing the similarity of principal cells discharge in response to the same incoming input.