Excitatory VTA to DH projections provide a valence signal to memory circuits

Abstract

The positive or negative value (valence) of past experiences is normally integrated into neuronal circuits that encode episodic memories and plays an important role in guiding behavior. Here, we show, using mouse behavioral models, that glutamatergic afferents from the ventral tegmental area to the dorsal hippocampus (VTA→DH) signal negative valence to memory circuits, leading to the formation of fear-inducing context memories and to contextspecific reinstatement of fear. To a lesser extent, these projections also contributed to opioidinduced place preference, suggesting a role in signaling positive valence as well, and thus a lack of dedicated polarity. Manipulations of VTA terminal activity were more effective in females and paralleled by sex differences in glutamatergic signaling. By prioritizing retrieval of negative and positive over neutral memories, the VTA→DH circuit can facilitate the selection of adaptive behaviors when current and past experiences are valence congruent.

New boundaries and dissociation of the mouse hippocampus along the dorsal‐ventral axis based on glutamatergic, GABAergic and catecholaminergic receptor densities

“…The dopaminergic projections from the ventral tegmental area and the substantia nigra to the dorsal hippocampus are sparse, while ventral hippocampus is densely innervated (Edelmann & Lessmann, 2018; Gasbarri, Sulli, & Packard, 1997). Further, additional routes for dopamine to effect dorsal hippocampal neurons have been described via release from noradrenergic containing neurons from the locus coeruleus (Han et al, 2020; Kempadoo, Mosharov, Choi, Sulzer, & Kandel, 2016; Takeuchi et al, 2016), the midbrain raphe nuclei and the nucleus accumbens (Edelmann & Lessmann, 2018). In addition, dorsal‐ventral hippocampus gradients have been reported in dopamine receptor gene expression (Gangarossa et al, 2012; Wei et al, 2018), but the functional contribution of these differences is yet not fully clear.…”

Nutrient sensing in the nucleus of the solitary tract mediates non-aversive suppression of feeding via inhibition of AgRP neurons

“…Sections were incubated in 10 mM sodium citrate at 80 °C for 20 min and then washed three times in PBS. Tissue was blocked for 1 h with 5% normal donkey serum or 5% normal goat serum (Abcam) at room temperature and incubated at 4 °C with primary antibodies against c-Fos (1:2000, Synaptic Systems, Cat# 226003; RRID: AB_2231974 ) [ 25 ], dsRed (1:1000, Clontech, Cat# 632392; RRID: AB_2801258 ) [ 26 ], GFP (1:1000, Abcam, Cat# ab13970; RRID: AB_300798 ) [ 27 ], TH (1:200, Cat# 22941; RRID: AB_572268 , Immunostar) [ 28 ], PrRP (1:1000, Abcam, Cat# ab251707), Ha (1:1000, Cell Signaling Technology, Ca# 3724; RRID: AB_1549585 ) [ 29 ] GFRAL (1:200, Thermo Fisher Scientific, Cat# PA5-47769; RRID: AB_2607220 ), and SYP (1:500, Synaptic Systems, Cat# 101 011; RRID: AB_887824 ) [ 30 ]. The sections were then mounted on slides and coverslipped with Prolong Diamond (Thermo Fisher Scientific).…”

Anatomy and Function of Ventral Tegmental Area Glutamate Neurons

“…However, this idea has been challenged due to the scarcity of dopaminergic projections found in the DH ( Kempadoo et al, 2016 ; Takeuchi et al, 2016 ). A recent study shows that VTA glutamate neurons send one-way projections to the DH ( Ntamati and Luscher, 2016 ; Adeniyi et al, 2020 ; Han et al, 2020 ). In addition, these DH-projecting glutamate neurons are TH negative and are mostly located in rostral VTA ( Han et al, 2020 ).…”

“…A recent study shows that VTA glutamate neurons send one-way projections to the DH ( Ntamati and Luscher, 2016 ; Adeniyi et al, 2020 ; Han et al, 2020 ). In addition, these DH-projecting glutamate neurons are TH negative and are mostly located in rostral VTA ( Han et al, 2020 ). Interestingly, postsynaptic currents in the granule cell layer of the dentate gyrus elicited by monosynaptic VTA projections are sensitive to both GABA and AMPA receptor antagonists, suggesting that the upstream VTA neurons co-release GABA and glutamate ( Ntamati and Luscher, 2016 ).…”