FIGURE 6.

Feed-forward computation of the field potentials (FPs) to explore the origin and volume conduction of theta in a hippocampus/habenula multicellular model of compartmental neurons. (A) Each model structure included only the cell types whose partially axialized morphologies make them candidates to generate significant extracellular currents (see section “Materials and Methods”). CA1 pyramidal cell (PC) were arranged in palisade, while habenular neurons were scattered over the tissue, although each class maintained the same orientation. The compartments in red mark the sites where inhibitory synaptic currents were injected at theta frequency on each cell type. (B) Model neurons were tuned with V-dependent channels to reproduce the reported firing behavior upon depolarizing current pulses (left column). Habenular neurons fire rebound spikes at the end of hyperpolarizing pulses (green arrow). The right column shows the responses to synaptic theta inputs. Note that the different firing modes shown are not relevant for FP production as the synaptic currents are user guided. FH, FV, Vert: fusiform horizontal, fusiform vertical, and vertical neurons (see section “Materials and Methods”). (C) Enlargement of an epoch [marked by ovals in (B)] showing the somatic membrane potential (V_m) for an PC and a FV cell during theta synaptic input. The theta-modulated V_m is about eight times larger in FV cells because of the smaller size and closer location of inputs to the soma. (D) Macroscopic model of the CA1 and LHb structures. The CA1 was built as five blocks of PC units arranged to jointly reproduce the entire septotemporal extent of the CA1 (>300,000 U). Only the position of the st. pyramidale is represented by the green blocks. The red line marks the sites in which computed FPs were selected to mimic an experimental linear recording and to build the V-profiles shown in (E). A, D, L: anterior, lateral, dorsal. (E) V-profiles during theta activity generated by distal inputs to CA1 PCs alone (purple) or in combination with some habenular cell types. Three different subcellular distributions of inputs to FV neurons are represented, from +100 μm basal to –200 apical (FV1), from +50 basal to –250 apical (FV2), and from −50 to −400 apical (FV3), and the soma was always free of synaptic input. The CA1 theta V-profile peaked in the st. lac-mol. (V_CA1) and decayed smoothly in ventral sites (i.e., volume conduction), traversing the LHb with high amplitude and the same polarity. In most conditions, LHb neurons produced theta potentials (white arrow, measured as V_LHb) that were negligible compared to volume-conducted – theta from the hippocampus. (F,G) The computed tridimensional voltage produced by the CA1 and/or LHb neurons at an instant of a theta wave marked by the vertical dash in the inset is represented as serial sagittal sections of the brain. Blue/yellow-red colors indicate negative and positive potentials (note that the zones with ± polarity reverse along the theta wave, which in turn is an artificial outcome of AC filtering).