Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Lateral habenula neurons signal step-by-step changes of reward prediction.

ABSTRACT: In real life, multiple objects of different values are mixed in a variety of environments. To survive, animals need to find rewarding objects that may be located but hidden in particular contexts (e.g., environments) with bad objects that are unassociated with reward. Then, animals and humans pay attention to the enriched environment so that they can find the rewarding object vigorously. How can the brain initiate such behavior based on the context? We thus created a behavioral task for monkeys in which multiple contextual events (environment, action cue) sequentially occurred before objects appeared. We then studied the lateral habenula (LHb), which inhibit dopamine neurons (Matsumoto and Hikosaka, 2007). LHb neurons showed phasic responses in each event step-by-step across the sequential events, whose direction (excitation or inhibition) corresponded to the immediate change of the predicted value. Moreover, LHb neurons sequentially compared detailed prediction errors based on their significance in multiple contexts.

SUBMITTER: Lee H

PROVIDER: S-EPMC9641246 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Lateral habenula neurons signal step-by-step changes of reward prediction.

Lee Hyunchan H Hikosaka Okihide O

iScience 20221027 11

In real life, multiple objects of different values are mixed in a variety of environments. To survive, animals need to find rewarding objects that may be located but hidden in particular contexts (e.g., environments) with bad objects that are unassociated with reward. Then, animals and humans pay attention to the enriched environment so that they can find the rewarding object vigorously. How can the brain initiate such behavior based on the context? We thus created a behavioral task for monkeys ...[more]

PMID: 36388993

Similar Datasets

Lateral habenula neurons signal errors in the prediction of reward information.

Project description:Humans and animals have the ability to predict future events, which they cultivate by continuously searching their environment for sources of predictive information. However, little is known about the neural systems that motivate this behavior. We hypothesized that information-seeking is assigned value by the same circuits that support reward-seeking, such that neural signals encoding reward prediction errors (RPEs) include analogous information prediction errors (IPEs). To test this, we recorded from neurons in the lateral habenula, a nucleus that encodes RPEs, while monkeys chose between cues that provided different chances to view information about upcoming rewards. We found that a subpopulation of lateral habenula neurons transmitted signals resembling IPEs, responding when reward information was unexpectedly cued, delivered or denied. These signals evaluated information sources reliably, even when the monkey's decisions did not. These neurons could provide a common instructive signal for reward-seeking and information-seeking behavior.

| S-EPMC3164948 | biostudies-literature

A unique population of ventral tegmental area neurons inhibits the lateral habenula to promote reward.

Project description:Lateral habenula (LHb) neurons convey aversive and negative reward conditions through potent indirect inhibition of ventral tegmental area (VTA) dopaminergic neurons. Although VTA dopaminergic neurons reciprocally project to the LHb, the electrophysiological properties and the behavioral consequences associated with selective manipulations of this circuit are unknown. Here, we identify an inhibitory input to the LHb arising from a unique population of VTA neurons expressing dopaminergic markers. Optogenetic activation of this circuit resulted in no detectable dopamine release in LHb brain slices. Instead, stimulation produced GABA-mediated inhibitory synaptic transmission, which suppressed the firing of postsynaptic LHb neurons in brain slices and increased the spontaneous firing rate of VTA dopaminergic neurons in vivo. Furthermore, in vivo activation of this pathway produced reward-related phenotypes that were dependent on intra-LHb GABAA receptor signaling. These results suggest that noncanonical inhibitory signaling by these hybrid dopaminergic-GABAergic neurons act to suppress LHb output under rewarding conditions.

| S-EPMC3873746 | biostudies-other

Tonic activity in lateral habenula neurons acts as a neutral valence brake on reward-seeking behavior.

Project description:Survival requires both the ability to persistently pursue goals and the ability to determine when it is time to stop, an adaptive balance of perseverance and disengagement. Neural activity in the lateral habenula (LHb) has been linked to negative valence, but its role in regulating the balance between engaged reward seeking and disengaged behavioral states remains unclear. Here, we show that LHb neural activity is tonically elevated during minutes-long periods of disengagement from reward-seeking behavior, both when due to repeated reward omission (negative valence) and when sufficient reward has been consumed (positive valence). Furthermore, we show that LHb inhibition extends ongoing reward-seeking behavioral states but does not prompt task re-engagement. We find no evidence for similar tonic activity changes in ventral tegmental area dopamine neurons. Our findings support a framework in which tonic activity in LHb neurons suppresses engagement in reward-seeking behavior in response to both negatively and positively valenced factors.

| S-EPMC9613558 | biostudies-literature

Stress transforms lateral habenula reward responses into punishment signals.

Project description:Neuronal activity in the lateral habenula (LHb), a brain region implicated in depression [C. D. Proulx, O. Hikosaka, R. Malinow, Nat. Neurosci. 17, 1146-1152 (2014)], decreases during reward and increases during punishment or reward omission [M. Matsumoto, O. Hikosaka, Nature 447, 1111-1115 (2007)]. While stress is a major risk factor for depression and strongly impacts the LHb, its effect on LHb reward signals is unknown. Here we image LHb neuronal activity in behaving mice and find that acute stress transforms LHb reward responses into punishment-like neural signals; punishment-like responses to reward omission also increase. These neural changes matched the onset of anhedonic behavior and were specific to LHb neurons that distinguished reward and its omission. Thus, stress distorts LHb responsivity to positive and negative feedback, which could bias individuals toward negative expectations, a key aspect of the proposed pathogenesis of depression [A. T. Beck, Depression: Clinical, Experimental, and Theoretical Aspects, sixth Ed (1967)].

| S-EPMC6589650 | biostudies-literature

The globus pallidus sends reward-related signals to the lateral habenula.

Project description:As a major output station of the basal ganglia, the globus pallidus internal segment (GPi) projects to the thalamus and brainstem nuclei thereby controlling motor behavior. A less well known fact is that the GPi also projects to the lateral habenula (LHb) which is often associated with the limbic system. Using the monkey performing a saccade task with positionally biased reward outcomes, we found that antidromically identified LHb-projecting neurons were distributed mainly in the dorsal and ventral borders of the GPi and that their activity was strongly modulated by expected reward outcomes. A majority of them were excited by the no-reward-predicting target and inhibited by the reward-predicting target. These reward-dependent modulations were similar to those in LHb neurons but started earlier than those in LHb neurons. These results suggest that GPi may initiate reward-related signals through its effects on the LHb, which then influences the dopaminergic and serotonergic systems.

| S-EPMC2638585 | biostudies-literature

Lateral Habenula Responses During Eye Contact in a Reward Conditioning Task.

Project description:For many animals, social interaction may have intrinsic reward value over and above its utility as a means to the desired end. Eye contact is the starting point of interactions in many social animals, including primates, and abnormal patterns of eye contact are present in many mental disorders. Whereas abundant previous studies have shown that negative emotions such as fear strongly affect eye contact behavior, modulation of eye contact by reward has received scant attention. Here we recorded eye movement patterns and neural activity in lateral habenula while monkeys viewed faces in the context of Pavlovian and instrumental conditioning tasks. Faces associated with larger rewards spontaneously elicited longer periods of eye contact from the monkeys, even though this behavior was not required or advantaged in the task. Concurrently, lateral habenula neurons were suppressed by faces signaling high value and excited by faces signaling low value. These results suggest that the reward signaling of lateral habenula may contribute to social behavior and disorders, presumably through its connections with the basal ganglia.

| S-EPMC8964066 | biostudies-literature

Identification of GABAergic neurons innervating the zebrafish lateral habenula.

Project description:Habenula neurons are constantly active. The level of activity affects mood and behaviour, with increased activity in the lateral habenula reflecting exposure to punishment and a switch to passive coping and depression. Here, we identify GABAergic neurons that could reduce activity in the lateral habenula of larval zebrafish. GAD65/67 immunohistochemistry and imaging of gad1b:DsRed transgenic fish suggest the presence of GABAergic terminals in the neuropil and between cell bodies in the lateral habenula. Retrograde tracing with the lipophilic dye DiD suggests that the former derives from the thalamus, while the latter originates from a group of cells in the posterior hypothalamus that are located between the posterior tuberal nucleus and hypothalamic lobes. Two-photon calcium imaging indicates that blue light causes excitation of thalamic GABAergic neurons and terminals in the neuropil, while a subpopulation of lateral habenula neurons show reduced intracellular calcium levels. Whole-cell electrophysiological recording indicates that blue light reduces membrane potential of lateral habenula neurons. These observations suggest that GABAergic input from the thalamus may mediate inhibition in the zebrafish lateral habenula. Mechanisms governing release of GABA from the neurons in the posterior hypothalamus, which are likely to be in the tuberomammillary nucleus, remain to be defined.

| S-EPMC7689879 | biostudies-literature

Lateral Habenula Glutamatergic Neurons Modulate Isoflurane Anesthesia in Mice.

Project description:Since their introduction in the 1840s, one of the largest mysteries of modern anesthesia are how general anesthetics create the state of reversible loss of consciousness. Increasing researchers have shown that neural pathways that regulate endogenous sleep-wake systems are also involved in general anesthesia. Recently, the Lateral Habenula (LHb) was considered as a hot spot for both natural sleep-wake and propofol-induced sedation; however, the role of the LHb and related pathways in the isoflurane-induced unconsciousness has yet to be identified. Here, using real-time calcium fiber photometry recordings in vivo, we found that isoflurane reversibly increased the activity of LHb glutamatergic neurons. Then, we selectively ablated LHb glutamatergic neurons in Vglut2-cre mice, which caused a longer induction time and less recovery time along with a decrease in delta-band power in mice under isoflurane anesthesia. Furthermore, using a chemogenetic approach to specifically activate LHb glutamatergic neurons shortened the induction time and prolonged the recovery time in mice under isoflurane anesthesia with an increase in delta-band power. In contrast, chemogenetic inhibition of LHb glutamatergic neurons was very similar to the effects of selective lesions of LHb glutamatergic neurons. Finally, optogenetic activation of LHb glutamatergic neurons or the synaptic terminals of LHb glutamatergic neurons in the rostromedial tegmental nucleus (RMTg) produced a hypnosis-promoting effect in isoflurane anesthesia with an increase in slow wave activity. Our results suggest that LHb glutamatergic neurons and pathway are vital in modulating isoflurane anesthesia.

| S-EPMC7969819 | biostudies-literature

Multiple timescales of memory in lateral habenula and dopamine neurons.

Project description:Midbrain dopamine neurons are thought to signal predictions about future rewards based on the memory of past rewarding experience. Little is known about the source of their reward memory and the factors that control its timescale. Here we recorded from dopamine neurons, as well as one of their sources of input, the lateral habenula, while animals predicted upcoming rewards based on the past reward history. We found that lateral habenula and dopamine neurons accessed two distinct reward memories: a short-timescale memory expressed at the start of the task and a near-optimal long-timescale memory expressed when a future reward outcome was revealed. The short- and long-timescale memories were expressed in different forms of reward-oriented eye movements. Our data show that the habenula-dopamine pathway contains multiple timescales of memory and provide evidence for their role in motivated behavior.

| S-EPMC2920878 | biostudies-literature

Serotonin modulates glutamatergic transmission to neurons in the lateral habenula.

Project description:The lateral habenula (LHb) is bilaterally connected with serotoninergic raphe nuclei, and expresses high density of serotonin receptors. However, actions of serotonin on the excitatory synaptic transmission to LHb neurons have not been thoroughly investigated. The LHb contains two anatomically and functionally distinct regions: lateral (LHbl) and medial (LHbm) divisions. We compared serotonin's effects on glutamatergic transmission across the LHb in rat brains. Serotonin bi-directionally and differentially modulated glutamatergic transmission. Serotonin inhibited glutamatergic transmission in higher percentage of LHbl neurons but potentiated in higher percentage of LHbm neurons. Magnitude of potentiation was greater in LHbm than in LHbl. Type 2 and 3 serotonin receptor antagonists attenuated serotonin's potentiation. The serotonin reuptake blocker, and the type 2 and 3 receptor agonists facilitated glutamatergic transmission in both LHbl and LHbm neurons. Thus, serotonin via activating its type 2, 3 receptors, increased glutamate release at nerve terminals in some LHb neurons. Our data demonstrated that serotonin affects both LHbm and LHbl. Serotonin might play an important role in processing information between the LHb and its downstream-targeted structures during decision-making. It may also contribute to a homeostatic balance underlying the neural circuitry between the LHb and raphe nuclei.

| S-EPMC4817146 | biostudies-other

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data