Dopamine ramps encode discounted future value on a moment-by-moment basis
…(VTA) and at the axon terminals in the nucleus accumbens (NAc), specifically in the me
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…(VTA) and at the axon terminals in the nucleus accumbens (NAc), specifically in the me
Adinazolam (ADZ) is one of the benzodiazepine-type new psychoactive substances (NPSs) with anxiolytic, anticonvulsant, and antidepressant effects. Although it is previously reported that high dose of ADZ administration impaired psychomotor performance and memory, abuse potential and drug dependence of ADZ have not been fully investigated. In this study, we evaluated whether ADZ has abuse potential, and lead in drug dependence and withdrawal symptoms when ADZ treatment was abruptly stopped. ADZ (0.01, 0.03, and 0.1 mg/kg/inf) increased intravenous self-administration in Sprague Dawley rats, sug
…also indicate aVMAT2 expression in the nucleus accumbens (NAcc)., As SUD engages common neural pathways involved in natural reward processing i
…Interestingly, Bmal1 expression in the nucleus accumbens, a striatal subregion known for its role in mediating reward processes, inhibits alcohol consumption in both males and females, thus indicating that other striatal sub
The advent of dLight, a class of genetically encoded dopamine sensor, has significantlyadvanced our ability to monitor real-time dopamine dynamics in living animals. The success ofdLight1.3b with its superior dynamic ranges has prompted the development of subsequentiterations of this sensor to broaden the applicability of in vivo dopamine monitoring, particularlyin brain regions characterized by sparse dopaminergic signaling. In this study, we present asystematic and extensive in vivo characterization of novel dLight variants (dLight3.6 &dLight3.8) in comparison to the dLight1.3b parents s
Nucleus Accumbens (Nacb) dopamine (DA) regulates behavioral activation and effort-related decision-making in motivated behaviors. DA depletion has been shown to induce anergia and fatigue in effort-based decision tasks. The Cerebral Dopamine Neurotrophic Factor (CDNF) promotes the survival and function of dopaminergic neurons, and it is used to restore midbrain dopaminergic neurons in animal models of Parkinson’s disease. However, little is known about the role of CDNF in Nacb and if this neurotrophic factor can be affected by factors such as sex or age, behavioral manipulations or drugs that
…area (VTA) that innervate the nucleus accumbens (NAcc) and the prefrontal cortex (PFC) are critical for the creation of reward associations, including social reward. We have previously identified functional dopaminergic alterat
The laterodorsal tegmentum (LDT) is a brainstem nucleus that sends direct projections to the nucleus accumbens (NAc), a key brain region involved in reward and motivation. We have previously shown that LDT-NAc inputs are crucial for reward value, triggering preference and shifting value of natural rewards. However, if and how these specific projections mediate the rewarding properties of drugs of abuse remains elusive. Importantly, ex-vivo studies showed that cocaine exposure triggers neuroplasticity changes in the LDT and in the NAc, suggesting that LDT-NAc circuitry may be an important targe
…central markers of inflammation in the nucleus accumbens (NAc), a region implicated in regulation of mood, motivation and locomotor activity. Forty-eight Wistar rats (24 male; 24 female) were separated into groups exposed to combinations of CUSD/non-CUSD and corticosterone (2
…on VTA DA subpopulations targeting nucleus accumbens (NAc) and amygdala (AMg) nuclei. NAc-projecting DA neurons are activated by nicotine and their optogenetic activation is reinforcin
…glycine receptors (GlyR) in the nucleus Accumbens (nAc) and treatment with GlyR agonists raise basal DA, attenuate alcohol-induced DA release in the nAc and reduce alcohol intake in rats. Combined treatment with varenicline+bupropion produces additive effects on nAc DA output and abolishes the alcohol deprivation effect (ADE) in rats, predictive of clinical efficacy. This study examines whether the gly
The hippocampus is thought to form the brain substrate of a cognitive map. While the spatial component of this map involves hippocampal ‘place’ cells, non-spatial features may require coupling with other brain areas. This could involve ‘hippocampal sequences’, endogenous activations of successive place cells representing entire trajectories at a highly accelerated rate. These sequences are paced by theta or ripple oscillations, and could participate in learning and memory, as well as goal-directed decision making. However, the association between hippocampal sequences and reward- and goal-rela
The traditional method in the development of drugs for neurodegenerative diseases, such as Alzheimer's or Parkinson's disease, necessitates the use of various animal models to assess complex behavioral changes. This process is not only time-consuming but also prone to misjudgments due to interspecies behavioral differences. In contrast, neural activity data gathered by head-mounted microscopy platforms represent integrated information that is relatively straightforward to interpret and exhibits low variability between species. This makes it an excellent resource for the development of correspo
…The nucleus accumbens (NAc), integral to the brain's reward circuitry, plays a crucial role in the initiation and continuation of maladaptive behaviors intrinsic to CUD. Leveraging advancements in neuroproteomics, we undertook an in-depth proteomic analysis of the NAc in a mouse model that spans membran
…ventral tegmental area (VTA) and the nucleus accumbens (NAc) is crucial in regulating memory, emotion, motivation, and behavior due to its responsibility to modulate dopamine. To better investigate the relationship between DA and addiction, more advanced mapping methods are necessary to monitor its production and propagation accurately and efficiently. In th
The Ventral Tegmental Area (VTA) is a crucial component of the brain's reward system and is known to regulate motivated behaviour. Recent studies have shown that activation of VTA dopaminergic (DA) neurons can stimulate anti-bacterial and anti-tumour immunity, suggesting a potential link between mental states and an organism's immune response to disease. However, the specific mechanisms underlying these peripheral effects are still unclear. Given that VTA-DA neurons project to multiple brain regions, and each pathway promote different behaviour we considered that also the immune effects of eac
…Nucleus Accumbens (Nacb) dopamine (DA) plays a major role in voluntary locomotion and in the activational component of motivated behaviors, including effort-related decision-making. The transcription factor Pitx3 is critical for the survival of mesolimbic DA neurons. Aphakia mice (Ak) have a mutation in Pitx3, which leads to a reduction in dorsal-striatal dopaminergic innervation and results in parkinsonian-like motor alterations. They also show a reduction in ventral-striatal DA, including Nacb. I
Glucagon like peptide (GLP-1) receptor agonists (GLP-1 RAs), such as Semaglutide, suppress food intake and are FDA approved to treat obesity. The primary mechanism of GLP-1 RAs involves interactions with the central nervous system, where GLP1 RA act in the hypothalamus or brainstem to reduce food intake. GLP-1 action on midbrain dopamine neurons in the VTA may also reduce food motivation and reward to suppress appetite. In addition to GLP1 RAs, new compounds with dual GLP1R and glucose-dependent insulinotropic polypeptide (GIP) receptor co-agonism, such as tirzepatide, show greater weight loss
…drugs increase dopamine in the nucleus accumbens (NAc), where it persistently shapes excitatory glutamate transmission, thereby hijacking natural reward processing. Recently, we provide evidence, from mice to humans, that psychostimulants and opiates alter DA-glutamate signal integration in the NAc through a drug-evoked heteromerization (i.e direct physical interaction) of glutamate NMDA receptors (NMDAR) with D1R or D2R. Using
…of dynorphin in the VTA arises from nucleus accumbens (NAc) D1-MSNs, and that dynorphin acts primarily on kappa opioid receptors (KORs), serving as negative feedback mechanism to modulate dopamine release. Thus, dynorphin signals may regulate dopamine dynamics and, in this way, contribute for r
The nucleus accumbens (NAc) is a key brain region involved in rewarding and aversive responses. The NAc is mainly composed of GABAergic medium spiny neurons (MSNs) expressing either dopamine receptor D1 or D2. Some studies propose an antagonist role of D1- and D2-MSNs, whereas others suggest that both populations play distinct, but not necessarily opposing roles in valence behaviour.Here, we used deep brain 1-photon calcium imaging to follow NAc D1- or D2-MSN activity in response to opposing valence stimuli and during associative learning. In addition, we used optogenetics to further unravel t
…dopamine (DA) pathway projecting to nucleus accumbens, (NAcb) modulates behavioral activation and effort exertion. Depletion of DA levels in Nacb leads to anergia and influences choices toward less effortful demanding options. DA function seems to be diminished with age. Our laboratory has developed behavioral tasks for rodents, including the PROG/sucrose task, for the study of effort-related choices linked to DA signaling in NAcb. Male Wistar rats of di
Basal amygdala (BA)-to-nucleus accumbens (NAc) projection neurons are integral to the circuitry of emotional processing. Recent studies have addressed whether neurons in this population(s) respond to reward, aversion or both emotional valences, but the focus has been on processing of physical emotional stimuli. Here, we extend this to salient social stimuli, whose processing is essential for the whole the animal kingdom and vital for maintaining individual physical and mental health. In male mice, an iterative study was conducted into engagement of BA-NAc neurons in response to social reward (
To behave optimally, animals build models of the world based on structural regularities to allow accurate prediction of the value of actions. Although powerful, the computational expense of updating these models limits their usefulness in ever-changing environments. Theoretical models have suggested that a way around these limitations is to separate the representation of structure from the associated value, allowing values to be rapidly updated when necessary. However, it is still unclear how this is implemented in the brain. To address this, we developed an odour-based task that requires mice