Conjunctive spatial and idiothetic codes are topographically organized in the GABAergic cells of the lateral septum

Abstract

The relevance of the hippocampal spatial code for downstream neuronal populations, in particular its main subcortical output, the lateral septum (LS), is still poorly understood. Here, we addressed this knowledge gap by first clarifying the organization of LS afferents and efferents via retrograde and anterograde trans-synaptic tracing. We found that mouse LS receives inputs from hippocampal subregions CA1, CA3, and subiculum, and in turn projects directly to the lateral hypothalamus (LH), ventral tegmental area (VTA), and medial septum (MS). Next, we functionally characterized the spatial tuning properties of LS GABAergic cells, the principal cells composing the LS, via calcium imaging combined with unbiased analytical methods. We identified a significant number of cells that are modulated by place (38.01%), speed (23.71%), acceleration (27.84%), and head-direction (23.09%), and conjunctions of these properties, with spatial tuning comparable to hippocampal CA1 and CA3 place cells. Bayesian decoding of position on the basis of LS place cells accurately reflected the location of the animal. The distributions of cells exhibiting these properties formed gradients along the anterior-posterior axis of the LS, directly reflecting the organization of hippocampal inputs to the LS. A portion of LS place cells showed stable fields over the course of multiple days, potentially reflecting long-term episodic memory. Together, our findings demonstrate that the LS accurately and robustly represents spatial and idiothetic information and is uniquely positioned to relay this information from the hippocampus to the VTA, LH, and MS, thus occupying a key position within this distributed spatial memory network.

Top-down regulation of motivated behaviors via lateral septum sub-circuits

“…Projections to the contralateral, congruent subnuclei were also detected” [ 46 ]. Consistently, anterograde trans-synaptic delivery of Cre recombinase in mice showed that cLS neurons innervated by dCA3 and dCA1 send long-range projections to the hypothalamus as well as collaterals to rLS [ 48 ]. These collaterals projecting to other LS regions are likely to provide lateral inhibition on antagonistic parallel pathways (see section 6 ).…”

Linking temporal coordination of hippocampal activity to memory function

“…Given that neural computations are highly compositional and increase in complexity and abstraction with every hierarchical level (Hubel and Wiesel, 1962;Moser et al, 2008), hippocampal activities are also relevant in the context of how downstream neurons integrate such signals (Buzsáki and Tingley, 2018). The lateral septum is the most prominent subcortical target of hippocampal projections (Risold and Swanson, 1996; Figure 2A) and contains GABAergic cells that display conjunctive tuning to spatial and selfmotion signals (including speed, acceleration, and head direction) similar to CA1 and CA3 pyramidal neurons (Wirtshafter and Wilson, 2019;Veldt et al, 2021). Additionally, the timing of action potentials of lateral septum neurons is locked to specific theta phases at different positions in space, such that the position of the animal can be accurately decoded by the phase at which lateral septum neurons fire (Tingley and Buzsáki, 2018).…”