Control of parallel hippocampal output pathways by amygdalar long-range inhibition.

Rawan Alsubaie,Daniel Regester,Ryan Ws Wee,Andrew F Macaskill,Jessica Passlack,Karyna Mishchanchuk,Anne Ritoux

doi:10.7554/elife.74758

Abstract

Projections from the basal amygdala (BA) to the ventral hippocampus (vH) are proposed to provide information about the rewarding or threatening nature of learned associations to support appropriate goal-directed and anxiety-like behaviour. Such behaviour occurs via the differential activity of multiple, parallel populations of pyramidal neurons in vH that project to distinct downstream targets, but the nature of BA input and how it connects with these populations is unclear. Using channelrhodopsin-2-assisted circuit mapping in mice, we show that BA input to vH consists of both excitatory and inhibitory projections. Excitatory input specifically targets BA- and nucleus accumbens-projecting vH neurons and avoids prefrontal cortex-projecting vH neurons, while inhibitory input preferentially targets BA-projecting neurons. Through this specific connectivity, BA inhibitory projections gate place-value associations by controlling the activity of nucleus accumbens-projecting vH neurons. Our results define a parallel excitatory and inhibitory projection from BA to vH that can support goal-directed behaviour.

Highlights

The hippocampus is key for episodic memory, learning and spatial navigation, as well as motivation, affect and anxiety (Gray and McNaughton, 2003; O’Keefe and Nadel, 1978; Strange et al, 2014; Wikenheiser and Schoenbaum, 2016)
We found that neurons sending input to ventral hippocampus (vH) were widely dispersed throughout the entire basal amygdala (BA), including in basolateral amygdala (BLA), basomedial amygdala (BMA), and medial amygdala (MEA), as well as in more cortical amygdala areas (Figure 1B-D, McDonald and Mott, 2016; Strange et al, 2014)
We 378 show that this novel projection exists in concert with a parallel excitatory projection, and that the presence of its inhibitory influence can dramatically shift vH output in response to BA activity

Summary

INTRODUCTION

The hippocampus is key for episodic memory, learning and spatial navigation, as well as motivation, affect and anxiety (Gray and McNaughton, 2003; O’Keefe and Nadel, 1978; Strange et al, 2014; Wikenheiser and Schoenbaum, 2016). VHPFC activity is proposed to support the resolution of approach avoidance conflict, and contribute to spatial working memory (Padilla Coreano et al, 2016; Sanchez-Bellot and MacAskill, 2021; Spellman et al, 2015), while vHBA activity is proposed to support contextual learning (Jimenez et al, 2018) It remains unclear how the activity of these distinct populations in vH is differentially controlled to promote these functions. Using a simple network model constrained by our electrophysiology recordings, we predicted that the ability of BA input to drive motivation- and value-promoting vH projections to NAc was dependent on the coactivation of both excitatory and inhibitory input from BA We confirmed these predictions using in vivo optogenetics and genetically targeted pharmacology to show that long range inhibition is required for the generation of spatial place preference. Together our results outline a novel inhibitory projection from amygdala to ventral hippocampus that defines the activity of vH output neurons, and is able to control hippocampal output to promote the formation of spatial place 83 preference

RESULTS

DISCUSSION

540 METHODS

Histology for experiments in Figure 6G-K