Reward behaviour is regulated by the strength of hippocampus–nucleus accumbens synapses

LeGates, Tara A.; Kvarta, Mark D.; Tooley, Jessica; Francis, T. Chase; Lobo, Mary Kay; Creed, Meaghan C.; Thompson, Scott M.

doi:10.1038/s41586-018-0740-8

Cited by 204 publications

(194 citation statements)

References 22 publications

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“…Interestingly, preclinical lesion and inactivation studies indicate that the more anterior and dorsal areas of the hippocampus have the largest role in spatial orienting and learning behaviors, while the posterior and ventral areas of the hippocampus, though still contributory to spatial navigation, appear to also participate in other realms of behavior (Bannerman et al 2004;Fanselow & Dong 2010;Kanoski & Grill 2015;Pennartz et al 2011;Strange et al 2014). Nevertheless, it has been shown that increased activity of the ventral hippocampus promotes conditioned place preference for social reward (LeGates et al 2018) while inactivation diminishes context-mediated drug Lasseter et al 2010;Rogers & See 2007;Sun & Rebec 2003) and alcohol reinstatement . Thus, the ventral hippocampus processes salient contextual information.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of the Ventral Hippocampus Increases Alcohol Drinking

Griffin¹,

Rinker

Woodward

et al. 2019

Preprint

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The function of the ventral hippocampus (vHC) supports many behaviors, including those related to reward seeking behaviors and drug addiction. We used a mouse model of alcohol dependence and relapse to investigate the role of the vHC in alcohol (ethanol) drinking. One experiment used a chemogenetic approach to inhibit vHC function while ethanol dependent and non-dependent mice had access to ethanol. Interestingly, the non-dependent mice expressing an inhibitory DREADD in the VHC showed a significant increase in ethanol drinking (~30%) after hM4Di DREADD activation with clozapine-n-oxide (CNO; 3 mg/kg, ip.) compared to vehicle. On the other hand, ethanol dependent mice, which were already drinking significantly more ethanol than non-dependent mice, only had a slight, non-significant increase in drinking after CNO challenge. In a separate group of dependent and non-dependent mice, GCaMP6f calcium-dependent activity was recorded in the vHC while mice were actively drinking ethanol. These data showed that once mice were rendered ethanol dependent and were drinking more ethanol than the non-dependent mice, calcium signaling in the ventral hippocampus decreased (~45%) in the ethanol dependent mice compared to the non-dependent mice. Together, these findings suggest that ethanol dependence reduces activity of the ventral hippocampus and that reduced function of this brain region contributes to increased ethanol drinking.

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Section: Introductionmentioning

confidence: 99%

Inhibition of the Ventral Hippocampus Increases Alcohol Drinking

Griffin¹,

Rinker

Woodward

et al. 2019

Preprint

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“…Further, studies have demonstrated distinct electrophysiological properties in MSN subtypes that correspond to morphological properties (Ade, Janssen, Ortinski, & Vicini, 2008;Cepeda et al, 2008;Chan et al, 2012;Chuhma, Tanaka, Hen, & Rayport, 2011;Gertler, Chan, & Surmeier, 2008;Kreitzer & Malenka, 2007;Ma et al, 2013;Pascoli et al, 2014;Willett et al, 2018). These differential properties, including their projection circuitry through the brain, can often give rise to differential action, motivational, and emotional behavioral outcomes (Creed, Ntamati, Chandra, Lobo, & Luscher, 2016;Ferguson et al, 2011;Francis et al, 2015;Heinsbroek et al, 2017;Hikida, Kimura, Wada, Funabiki, & Nakanishi, 2010;Kravitz et al, 2010;Kravitz, Tye, & Kreitzer, 2012;LeBlanc et al, 2018;LeGates et al, 2018;Lobo et al, 2010;Massaly et al, 2019;Rothwell et al, 2014). These differential properties, including their projection circuitry through the brain, can often give rise to differential action, motivational, and emotional behavioral outcomes (Creed, Ntamati, Chandra, Lobo, & Luscher, 2016;Ferguson et al, 2011;Francis et al, 2015;Heinsbroek et al, 2017;Hikida, Kimura, Wada, Funabiki, & Nakanishi, 2010;Kravitz et al, 2010;Kravitz, Tye, & Kreitzer, 2012;LeBlanc et al, 2018;LeGates et al, 2018;Lobo et al, 2010;Massaly et al, 2019;Rothwell et al, 2014).…”

mentioning

confidence: 99%

“…These properties are altered in MSN subtypes in diseased states including neurodegeneration, addiction, stress-induced affective behavior, pain, and repetitive behaviors (Chen et al, 2017;Fieblinger et al, 2014;Francis et al, 2015Francis et al, , 2017Galvan, Andre, Wang, Cepeda, & Levine, 2012;Graziane et al, 2016;Hearing et al, 2016;Heinsbroek et al, 2017;Kim, Park, Lee, Park, & Kim, 2011;LeGates et al, 2018;Lim, Huang, Grueter, Rothwell, & Malenka, 2012;Massaly et al, 2019;Ren et al, 2016;Rothwell et al, 2014;Schwartz et al, 2014;Terrier, Luscher, & Pascoli, 2016). These differential properties, including their projection circuitry through the brain, can often give rise to differential action, motivational, and emotional behavioral outcomes (Creed, Ntamati, Chandra, Lobo, & Luscher, 2016;Ferguson et al, 2011;Francis et al, 2015;Heinsbroek et al, 2017;Hikida, Kimura, Wada, Funabiki, & Nakanishi, 2010;Kravitz et al, 2010;Kravitz, Tye, & Kreitzer, 2012;LeBlanc et al, 2018;LeGates et al, 2018;Lobo et al, 2010;Massaly et al, 2019;Rothwell et al, 2014). Additionally, in some of these pathological states, mitochondrial properties are disrupted in MSNs Hollis et al, 2015;Larrieu et al, 2017).…”

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confidence: 99%

Differential mitochondrial morphology in ventral striatal projection neuron subtypes

Chandra

Calarco

Lobo

2019

J of Neuroscience Research

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The two striatal projection neuron subtypes (medium spiny neurons‐ MSNs), those enriched in dopamine receptor 1 versus 2 (D1‐MSNs and D2‐MSNs), display dichotomous properties at the level of the transcriptome, projections, morphology, and electrophysiology. Recent work illustrates dichotomous mitochondrial length in NAc MSN subtype dendrites after cocaine self‐administration, with a shift toward smaller mitochondria, due to enhanced fission, occurring in D1‐MSN dendrites and a shift toward larger mitochondria in D2‐MSN dendrites. However, to date there has been no comparison of mitochondrial morphological properties between MSN subtypes. In this study, we examine mitochondrial morphology in NAc D1‐MSNs versus D2‐MSNs. We observe an increase in the frequency of smaller length mitochondria in D2‐MSN dendrites relative to D1‐MSN dendrites, while D1‐MSN dendrites display an increase in larger length mitochondria. The differences in mitochondrial length occur in both NAc core and shell, although to a greater extent in NAc core. Finally, we demonstrate that the mitochondrial fusion molecule, Opa1, is differentially expressed in NAc MSN subtypes, with D1‐MSNs displaying higher expression of Opa1 ribosome‐associated mRNA. The difference in Opa1 levels may account for the bias toward enhanced smaller mitochondria in D2‐MSNs and enhanced larger mitochondria in D1‐MSNs. Collectively, our study demonstrates differential mitochondrial size and a potential molecular mediator of these mitochondrial differences in NAc MSN subtypes.

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“…4d). Given 27 the strong anatomical projections from the vH to limbic brain areas involved in reward 28 processing 5,6,[8][9][10][11] , we expected that vSWRs would show a similar or greater level of reward 29 modulation. Instead, vSWRs maintained a similar rate on rewarded and error trials and were not 30 enhanced during early novelty (Fig.…”

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confidence: 99%

“…3, NREM sleep periods were defined by exclusion of REM sleep as 1 defined previously 37 . Specifically, REM periods were detected as times when the ratio of Hilbert 2 amplitudes of theta (5)(6)(7)(8)(9)(10)(11) to delta (1)(2)(3)(4), referenced to cerebellar ground, exceeded a per-3 animal threshold of 1.4-1.7 for at least 10 s. 4…”

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confidence: 99%

Dorsal and ventral hippocampus engage opposing networks in the nucleus accumbens

Sosa

Joo

Frank

2019

Preprint

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2Memories of positive experiences require the brain to link places, events, and reward outcomes. 3Neural processing underlying the association of spatial experiences with reward is thought to 4 depend on interactions between the hippocampus and the nucleus accumbens (NAc) 1-9 . 5Hippocampal projections to the NAc arise from both the ventral hippocampus (vH) and the 6 dorsal hippocampus (dH) 6-12 , and studies using optogenetic interventions have demonstrated that 7 either vH 5,6 or dH 7 input to the NAc can support behaviors dependent on spatial-reward 8 associations. It remains unclear, however, whether dH, vH, or both coordinate memory 9processing of spatial-reward information in the hippocampal-NAc circuit under normal 10 conditions. Times of memory reactivation within and outside the hippocampus are marked by 11 hippocampal sharp-wave ripples (SWRs) [13][14][15][16][17][18][19] , discrete events which facilitate investigation of 12 inter-regional information processing. It is unknown whether dH and vH SWRs act in concert or 13 separately to engage NAc neuronal networks, and whether either dH or vH SWRs are 14 preferentially linked to spatial-reward representations. Here we show that dH and vH SWRs 15 occur asynchronously in the awake state and that NAc spatial-reward representations are 16 selectively activated during dH SWRs. We performed simultaneous extracellular recordings in 17 the dH, vH, and NAc of rats learning and performing an appetitive spatial task and during 18 sleep. We found that individual NAc neurons activated during SWRs from one subdivision of 19 the hippocampus were typically suppressed or unmodulated during SWRs from the other. NAc 20 neurons activated during dH versus vH SWRs showed markedly different task-related firing 21 patterns. Only dH SWR-activated neurons were tuned to similarities across spatial paths and past 22 reward, indicating a specialization for the dH-NAc, but not vH-NAc, network in linking reward 23 to discrete spatial paths. These temporally and anatomically separable hippocampal-NAc 24 interactions suggest that dH and vH coordinate opposing channels of mnemonic processing in 25 the NAc. 26

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Reward behaviour is regulated by the strength of hippocampus–nucleus accumbens synapses

Cited by 204 publications

References 22 publications

Inhibition of the Ventral Hippocampus Increases Alcohol Drinking

Inhibition of the Ventral Hippocampus Increases Alcohol Drinking

Differential mitochondrial morphology in ventral striatal projection neuron subtypes

Dorsal and ventral hippocampus engage opposing networks in the nucleus accumbens

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