Abstract
Specific classes of GABAergic neurons play specific roles in regulating information processing in the brain. In the hippocampus, two major classes, parvalbumin-expressing (PV+) and somatostatin-expressing (SST+), differentially regulate endogenous firing patterns and target subcellular compartments of principal cells. How these classes regulate the flow of information throughout the hippocampus is poorly understood. We hypothesize that PV+ and SST+ interneurons in the dentate gyrus (DG) and CA3 differentially modulate CA3 patterns of output, thereby altering the influence of CA3 on CA1. We find that while suppressing either interneuron class increases DG and CA3 output, the effects on CA1 were very different. Suppressing PV+ interneurons increases local field potential signatures of coupling from CA3 to CA1 and decreases signatures of coupling from entorhinal cortex to CA1; suppressing SST+ interneurons has the opposite effect. Thus, DG and CA3 PV+ and SST+ interneurons bidirectionally modulate the flow of information through the hippocampal circuit.
Highlights
GABAergic interneurons regulate principal cell input and output and act as hubs for controlling network activity throughout the brain (McKenzie, 2017)
We found that while suppression of either interneuron type led to an increase in dentate gyrus (DG) and CA3 spiking output, suppressing PV+ interneurons increased signatures of CA3 coupling to CA1 and decreased those of entorhinal cortex (EC) coupling to CA1, while suppressing SST+ interneurons decreased signatures of CA3 coupling to CA1 and increased those of EC coupling to CA1
In a second cohort of mice implanted with a four-shank electrode to enable recordings from all hippocampal subregions, we found that suppressing either class increased the extent to which DG and CA3, but not CA1, multiunit activity (MUA) increased during sharp-wave ripple (SWR) (Figure 3B)
Summary
GABAergic interneurons regulate principal cell input and output and act as hubs for controlling network activity throughout the brain (McKenzie, 2017). SST+ interneurons mainly target distal apical dendrites, which receive extrahippocampal excitatory inputs from the EC and medial septum, and gate the influence of those pathways, thereby affecting the magnitude of principal cell spiking (Blasco-Iban ̃ ez and Freund, 1995; Klausberger and Somogyi, 2008; Lovett-Barron et al, 2012; Sik et al, 1995, 1997; Takacs et al, 2012). These cells receive primarily local inputs from pyramidal cells and provide feedback inhibition (Freund and Buzsaki, 1996; Wheeler et al, 2015). Consistent with these patterns of inputs, potentiation of PV+ interneurons attenuates CA3 inputs while potentiation of CA1 SST+ interneurons attenuates EC inputs (Fernandez-Ruiz et al, 2017; Udakis et al, 2020)
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