Control of Parallel Hippocampal Output Pathways by Amygdalar Long-Range Inhibition

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.

Internal state dependent control of feeding behaviour via hippocampal ghrelin signalling

“…We hypothesised that this dramatic decrease in activity may be due to plasticity of inhibitory connectivity. To test this, we injected mice with two colours of retrobeads -one in NAc and one in LH (AlSubaie et al, 2021;Sanchez-Bellot and MacAskill, 2021;Wee and MacAskill, 2020). This allowed us, two weeks later, to inject either PBS or ghrelin i.p and after 20 minutes prepare acute slices where we could visualise and record from NAc and LH-projecting vS neurons in acute slices from the same mice (Figure 5A).…”

“…It is becoming increasingly understood that the hippocampus not only encodes the relationships between distinct cues in the environment (Eichenbaum, 2017;Rudy and Sutherland, 1995), but also the value of outcomes (Knudsen and Wallis, 2021;Lee et al, 2012). For example, the hippocampal-to-NAc projection has been proposed to be important for the learning of value associations in physical and abstract dimensions (AlSubaie et al, 2021;Duncan et al, 2018;Ito et al, 2008;LeGates et al, 2018;Trouche et al, 2019), and to relay these signals to ventral striatum (Pennartz et al, 2011). This ability is proposed to allow the utilisation of past experience to anticipate the outcome of upcoming behaviour.…”

“…However, while it is clear that motivational state affects hippocampal processing, and that hippocampal dysfunction impairs hunger dependent behaviour, how hippocampal circuitry directly influences internal state dependent feeding behaviour, and the cellular and circuit mechanisms underlying this ability remain unknown. This is compounded by the fact that vS is composed of multiple, non-overlapping and functionally distinct parallel projections to distinct downstream areas (AlSubaie et al, 2021;Cembrowski and Spruston, 2019;Sanchez-Bellot and MacAskill, 2021;Soltesz and Losonczy, 2018;Wee and MacAskill, 2020). For example, neurons in vS that project to the nucleus accumbens (NAc) have been shown to preferentially represent and control motivation and value (AlSubaie et al, 2021;Britt et al, 2012;LeGates et al, 2018;Trouche et al, 2019).…”

“…This is compounded by the fact that vS is composed of multiple, non-overlapping and functionally distinct parallel projections to distinct downstream areas (AlSubaie et al, 2021;Cembrowski and Spruston, 2019;Sanchez-Bellot and MacAskill, 2021;Soltesz and Losonczy, 2018;Wee and MacAskill, 2020). For example, neurons in vS that project to the nucleus accumbens (NAc) have been shown to preferentially represent and control motivation and value (AlSubaie et al, 2021;Britt et al, 2012;LeGates et al, 2018;Trouche et al, 2019). Similarly, a separate population of neurons projecting to the lateral hypothalamus (LH) have been shown to be recruited during salient environments and during learning of food associations (Hsu et al, 2015;Jimenez et al, 2018;Mohammad et al, 2021).…”

“…Both of these populations of neurons are therefore well placed to control anticipatory feeding related behaviour (Hsu et al, 2015;Reed et al, 2018;Yang et al, 2020). While this makes vH ideally placed to powerfully control motivational and hunger-related behaviour, each population has distinct influence on ongoing behaviour (AlSubaie et al, 2021;Britt et al, 2012;Hsu et al, 2015;Jimenez et al, 2018;LeGates et al, 2018;Mohammad et al, 2021;Trouche et al, 2019). Thus, how these populations are uniquely used during feeding behaviour, and how they are influenced by hunger and peripheral ghrelin, remains unknown.…”