-
Neuron May 2019The mesocorticolimbic pathway is canonically known as the "reward pathway." Embedded within the center of this circuit is the striatum, a massive and complex network hub... (Review)
Review
The mesocorticolimbic pathway is canonically known as the "reward pathway." Embedded within the center of this circuit is the striatum, a massive and complex network hub that synthesizes motivation, affect, learning, cognition, stress, and sensorimotor information. Although striatal subregions collectively share many anatomical and functional similarities, it has become increasingly clear that it is an extraordinarily heterogeneous region. In particular, the nucleus accumbens (NAc) medial shell has repeatedly demonstrated that the rules dictated by more dorsal aspects of the striatum do not apply or are even reversed in functional logic. These discrepancies are perhaps most easily captured when isolating the functions of various neuromodulatory peptide systems within the striatum. Endogenous peptides are thought to play a critical role in modulating striatal signals to either amplify or dampen evoked behaviors. Here we describe the anatomical-functional backdrop upon which several neuropeptides act within the NAc to modulate behavior, with a specific emphasis on nucleus accumbens medial shell and stress responsivity. Additionally, we propose that, as the field continues to dissect fast neurotransmitter systems within the NAc, we must also provide considerable contextual weight to the roles local peptides play in modulating these circuits to more comprehensively understand how this important subregion gates motivated behaviors.
Topics: Corpus Striatum; Humans; Interneurons; Motivation; Neurons; Neuropeptides; Nucleus Accumbens
PubMed: 31071288
DOI: 10.1016/j.neuron.2019.03.003 -
Cell Reports Aug 2022Social behaviors are among the most important motivated behaviors. How dopamine (DA), a "reward" signal, releases during social behaviors has been a topic of interest...
Social behaviors are among the most important motivated behaviors. How dopamine (DA), a "reward" signal, releases during social behaviors has been a topic of interest for decades. Here, we use a genetically encoded DA sensor, GRAB, to record DA activity in the nucleus accumbens (NAc) core during various social behaviors in male and female mice. We find that DA releases during approach, investigation and consummation phases of social behaviors signal animals' motivation, familiarity of the social target, and valence of the experience, respectively. Positive and negative social experiences evoke opposite DA patterns. Furthermore, DA releases during mating and fighting are sexually dimorphic with a higher level in males than in females. At the functional level, increasing DA in NAc enhances social interest toward a familiar conspecific and alleviates defeat-induced social avoidance. Altogether, our results reveal complex information encoded by NAc DA activity during social behaviors and their multistage functional roles.
Topics: Animals; Dopamine; Female; Male; Mice; Motivation; Nucleus Accumbens; Reward; Social Behavior
PubMed: 36001967
DOI: 10.1016/j.celrep.2022.111246 -
Nature Neuroscience Dec 2021The nucleus accumbens (NAc) plays an important role in regulating multiple behaviors, and its dysfunction has been linked to many neural disorders. However, the...
The nucleus accumbens (NAc) plays an important role in regulating multiple behaviors, and its dysfunction has been linked to many neural disorders. However, the molecular, cellular and anatomic heterogeneity underlying its functional diversity remains incompletely understood. In this study, we generated a cell census of the mouse NAc using single-cell RNA sequencing and multiplexed error-robust fluorescence in situ hybridization, revealing a high level of cell heterogeneity in this brain region. Here we show that the transcriptional and spatial diversity of neuron subtypes underlie the NAc's anatomic and functional heterogeneity. These findings explain how the seemingly simple neuronal composition of the NAc achieves its highly heterogenous structure and diverse functions. Collectively, our study generates a spatially resolved cell taxonomy for understanding the structure and function of the NAc, which demonstrates the importance of combining molecular and spatial information in revealing the fundamental features of the nervous system.
Topics: Animals; Brain; In Situ Hybridization, Fluorescence; Mice; Neurons; Nucleus Accumbens
PubMed: 34663959
DOI: 10.1038/s41593-021-00938-x -
Science (New York, N.Y.) Sep 2016The medial temporal lobe, including the hippocampus, has been implicated in social memory. However, it remains unknown which parts of these brain regions and their...
The medial temporal lobe, including the hippocampus, has been implicated in social memory. However, it remains unknown which parts of these brain regions and their circuits hold social memory. Here, we show that ventral hippocampal CA1 (vCA1) neurons of a mouse and their projections to nucleus accumbens (NAc) shell play a necessary and sufficient role in social memory. Both the proportion of activated vCA1 cells and the strength and stability of the responding cells are greater in response to a familiar mouse than to a previously unencountered mouse. Optogenetic reactivation of vCA1 neurons that respond to the familiar mouse enabled memory retrieval and the association of these neurons with unconditioned stimuli. Thus, vCA1 neurons and their NAc shell projections are a component of the storage site of social memory.
Topics: Animals; CA1 Region, Hippocampal; Cerebral Ventricles; Female; Male; Mental Recall; Mice; Mice, Inbred C57BL; Mice, Transgenic; Nucleus Accumbens; Optogenetics; Pyramidal Cells; Social Behavior
PubMed: 27708103
DOI: 10.1126/science.aaf7003 -
Cell Reports Feb 2023The nucleus accumbens (NAc) plays an important role in motivation and reward processing. Recent studies suggest that different NAc subnuclei differentially contribute to...
The nucleus accumbens (NAc) plays an important role in motivation and reward processing. Recent studies suggest that different NAc subnuclei differentially contribute to reward-related behaviors. However, how reward is encoded in individual NAc neurons remains unclear. Using in vivo single-cell resolution calcium imaging, we find diverse patterns of reward encoding in the medial and lateral shell subdivision of the NAc (NAcMed and NAcLat, respectively). Reward consumption increases NAcLat activity but decreases NAcMed activity, albeit with high variability among neurons. The heterogeneity in reward encoding could be attributed to differences in their synaptic inputs and transcriptional profiles. Specific optogenetic activation of Nts-positive neurons in the NAcLat promotes positive reinforcement, while activation of Cartpt-positive neurons in the NAcMed induces behavior aversion. Collectively, our study shows the organizational and transcriptional differences in NAc subregions and provides a framework for future dissection of NAc subregions in physiological and pathological conditions.
Topics: Nucleus Accumbens; Neurons; Motivation; Reward
PubMed: 36753418
DOI: 10.1016/j.celrep.2023.112069 -
Frontiers in Neural Circuits 2022Maladaptive changes in the neural circuits associated with reward and aversion result in some common symptoms, such as drug addiction, anxiety, and depression.... (Review)
Review
Maladaptive changes in the neural circuits associated with reward and aversion result in some common symptoms, such as drug addiction, anxiety, and depression. Historically, the study of these circuits has been hampered by technical limitations. In recent years, however, much progress has been made in understanding the neural mechanisms of reward and aversion owing to the development of technologies such as cell type-specific electrophysiology, neuronal tracing, and behavioral manipulation based on optogenetics. The aim of this paper is to summarize the latest findings on the mechanisms of the neural circuits associated with reward and aversion in a review of previous studies with a focus on the ventral tegmental area (VTA), nucleus accumbens (NAc), and basal forebrain (BF). These findings may inform efforts to prevent and treat mental illnesses associated with dysfunctions of the brain's reward and aversion system.
Topics: Reward; Ventral Tegmental Area; Nucleus Accumbens; Basal Forebrain; Neurons
PubMed: 36389177
DOI: 10.3389/fncir.2022.1002485 -
The Journal of Neuroscience : the... Feb 2022Appropriate responding to threat and reward is essential to survival. The nucleus accumbens core (NAcc) is known to support and organize reward behavior. The NAcc is...
Appropriate responding to threat and reward is essential to survival. The nucleus accumbens core (NAcc) is known to support and organize reward behavior. The NAcc is also necessary to fully discriminate threat and safety cues. To directly reveal NAcc threat firing, we recorded single-unit activity from seven female rats undergoing pavlovian fear discrimination. Rats fully discriminated danger, uncertainty, and safety cues, and most NAcc neurons showed the greatest firing change to danger and uncertainty. Heterogeneity in cue and reward firing led us to identify distinct functional populations. One NAcc population signaled threat, specifically decreasing firing to danger and uncertainty cues. A separate population signaled Bidirectional Valence, decreasing firing to the danger cue (negative valence), but increasing firing to reward (positive valence). The results reveal the NAcc to be a source of threat information and a more general valence hub. The nucleus accumbens core (NAcc) is synonymous with reward. Yet, anatomy, neurotoxic lesions, and optogenetic manipulation implicate the NAcc in threat. Here, we directly revealed NAcc threat firing by recording single-unit activity during multicue fear discrimination. Most cue-responsive NAcc neurons markedly altered firing to threat cues. Finer analyses revealed a NAcc population signaling threat, specifically decreasing firing to danger and uncertainty cues; and a NAcc population signaling Bidirectional Valence, increasing firing to reward but decreasing firing to the danger cue. The results reveal the NAcc to be a source of threat information and a valence hub.
Topics: Acoustic Stimulation; Action Potentials; Animals; Discrimination Learning; Fear; Female; Nucleus Accumbens; Rats; Rats, Long-Evans
PubMed: 34764160
DOI: 10.1523/JNEUROSCI.1107-21.2021 -
Trends in Pharmacological Sciences Mar 2018Commonalities in addictive behavior, such as craving, stimuli-driven drug seeking, and a high propensity for relapse following abstinence, have pushed for a unified... (Review)
Review
Commonalities in addictive behavior, such as craving, stimuli-driven drug seeking, and a high propensity for relapse following abstinence, have pushed for a unified theory of addiction that encompasses most abused substances. This unitary theory has recently been challenged - citing distinctions in structural neural plasticity, biochemical signaling, and neural circuitry to argue that addiction to opioids and psychostimulants is behaviorally and neurobiologically distinct. Recent more selective examination of drug-induced plasticity has highlighted that these two drug classes promote an overall reward circuitry signaling overlap through modifying excitatory synapses in the nucleus accumbens - a key constituent of the reward system. We discuss adaptations in presynaptic/postsynaptic and extrasynaptic glutamate signaling produced by opioids and psychostimulants, and their relevance to circuit remodeling and addiction-related behavior - arguing that these core neural adaptations are important targets for developing pharmacotherapies to treat addiction to multiple drugs.
Topics: Analgesics, Opioid; Animals; Central Nervous System Stimulants; Excitatory Amino Acid Agents; Humans; Neuronal Plasticity; Nucleus Accumbens; Psychotropic Drugs; Receptors, Glutamate; Synaptic Transmission
PubMed: 29338873
DOI: 10.1016/j.tips.2017.12.004 -
The Neuroscientist : a Review Journal... Apr 2007The ability to form associations between predictive environmental events and rewarding outcomes is a fundamental aspect of learned behavior. This apparently simple... (Review)
Review
The ability to form associations between predictive environmental events and rewarding outcomes is a fundamental aspect of learned behavior. This apparently simple ability likely requires complex neural processing evolved to identify, seek, and use natural rewards and redirect these activities based on updated sensory information. Emerging evidence from both animal and human research suggests that this type of processing is mediated in part by the nucleus accumbens (NAc) and a closely associated network of brain structures. The NAc is required for a number of reward-related behaviors and processes specific information about reward availability, value, and context. In addition, this structure is critical for the acquisition and expression of most Pavlovian stimulus-reward relationships, and cues that predict rewards produce robust changes in neural activity in the NAc. Although processing within the NAc may enable or promote Pavlovian reward learning in natural situations, it has also been implicated in aspects of human drug addiction, including the ability of drug-paired cues to control behavior. This article provides a critical review of the existing animal and human literature concerning the role of the NAc in Pavlovian learning with nondrug rewards and considers some clinical ture concerning the role of the NAc in Pavlovian learning with nondrug implications of these findings.
Topics: Animals; Brain; Conditioning, Psychological; Cues; Humans; Learning; Nerve Net; Nucleus Accumbens; Reward; Substance-Related Disorders
PubMed: 17404375
DOI: 10.1177/1073858406295854 -
Cell Reports Mar 2020The nucleus accumbens (NAc) contributes to behavioral inhibition and compulsions, but circuit mechanisms are unclear. Recent evidence suggests that amygdala and thalamic...
The nucleus accumbens (NAc) contributes to behavioral inhibition and compulsions, but circuit mechanisms are unclear. Recent evidence suggests that amygdala and thalamic inputs exert opposing control over behavior, much like direct and indirect pathway output neurons. Accordingly, opponent processes between these NAc inputs or cell types may underlie efficient reward seeking. We assess the contributions of these circuit elements to mouse operant behavior during recurring conditions when reward is and is not available. Although direct pathway stimulation is rewarding and indirect pathway stimulation aversive, the activity of both cell types is elevated during periods of behavioral suppression, and the inhibition of either cell-type selectively increases unproductive reward seeking. Amygdala and thalamic inputs are also necessary for behavioral suppression, even though they both support self-stimulation and innervate different NAc subregions. These data suggest that efficient reward seeking relies on complementary activity across NAc cell types and inputs rather than opponent processes between them.
Topics: Amygdala; Animals; Behavior, Animal; Cell Body; Female; Light; Male; Mice, Inbred C57BL; Mice, Transgenic; Neurons; Nucleus Accumbens; Reward; Thalamus
PubMed: 32187545
DOI: 10.1016/j.celrep.2020.02.095