Diversity of LFPs Activated in Different Target Regions by a Common CA3 Input

Abstract

Identifying the pathways contributing to local field potential (LFP) events and oscillations is essential to determine whether synchronous interregional patterns indicate functional connectivity. Here, we studied experimentally and numerically how different target structures receiving input from a common population shape their LFPs. We focused on the bilateral CA3 that sends gamma-paced excitatory packages to the bilateral CA1, the lateral septum, and itself (recurrent input). The CA3-specific contribution was isolated from multisite LFPs in target regions using spatial discrimination techniques. We found strong modulation of LFPs by target-specific features, including the morphology and population arrangement of cells, the timing of CA3 inputs, volume conduction from nearby targets, and co-activated inhibition. Jointly they greatly affect the LFP amplitude, profile, and frequency characteristics. For instance, ipsilateral (Schaffer) LFPs occluded contralateral ones, and septal LFPs arise mostly from remote sources while local contribution from CA3 input was minor. In the CA3 itself, gamma waves have dual origin from local networks: in-phase excitatory and nearly antiphase inhibitory. Also, waves may have different duration and varying phase in different targets. These results indicate that to explore the cellular basis of LFPs and the functional connectivity between structures, besides identifying the origin population/s, target modifiers should be considered.

Local Field Potentials: Myths and Misunderstandings

“…Besides, it is important to keep in mind that the proportion of local and remote contributions at any site cannot be ascertained from a single recording point. Indeed, in many brain structures most of the FP activity actually comes from remote sites since the local generators are weak (Martín-Vázquez et al, 2016). This is critical in studies of functional connectivity for which single-site recordings are strongly discouraged.…”

“…It is therefore absolutely necessary to disentangle the temporal fluctuations produced by each of the contributing pathways in order to establish a quantitative relationship with the activity of a single afferent population. So far, the only approaches providing acceptable separation that maintains complete temporal resolution of the mixing sources are the spatial discrimination techniques (Makarova et al, 2011; Fernández-Ruiz and Herreras, 2013; Martín-Vázquez et al, 2013, 2016; Benito et al, 2014, 2016; Głąbska et al, 2014; Schomburg et al, 2014). …”

“…In addition, concurrent (phase-coupled) gamma sources in the CA1 and CA3 pyramidal cells modify each other's features in function of the orientation of the respective dipoles. For example, Schaffer gamma LFPs in the CA1 increase in magnitude, and change their spatial profile and site of reversal (Martín-Vázquez et al, 2016). So far, such interactions have been studied only in the hippocampus, but they can be expected for any other structure.…”

“…Indeed, none of these observations rule out cases where interneurons set the clock for excitatory neurons to build LFP oscillations in their targets, such as was found for those mediated by the Schaffer or the lateral and medial Perforant Pathways in the CA1 and Dentate Gyrus (Fernández-Ruiz et al, 2012; Benito et al, 2014; Schomburg et al, 2014). In these cases, the origin of oscillatory LFPs is in excitatory neurons of the CA3 and entorhinal cortex, respectively, or through the excitatory recurrent pathway in the CA3 itself (Martín-Vázquez et al, 2016). These excitatory gamma oscillations are phase locked with others of truly GABAergic origin in the same region with which they blend in native LFPs (ibid.…”

“…On account of structure, strong synaptic inputs may contribute negligibly to LFPs while others that have a reduced impact on targeted units set up large LFPs. For instance the functionally chief excitatory input from the ipsilateral CA3 to the CA1 produces LFPs 5–10 times smaller than theta oscillations, and the important contralateral input is nearly completely occluded in LFPs (Martín-Vázquez et al, 2016). Meanwhile, powerful basket cell somatic inhibition that governs cell output in the CA1 produces minimal LFPs (Benito et al, 2014).…”