scholarly journals Coherent activity at three major lateral hypothalamic neural outputs controls the onset of motivated behavior responses

2021 ◽  
Author(s):  
Ekaterina Martianova ◽  
Alicia Pageau ◽  
Nikola Pausic ◽  
Tommy Doucet Gentiletti ◽  
Danahe Leblanc ◽  
...  
Keyword(s):  
Behavioral Responses ◽  
Dopamine Neurons ◽  
Sucrose Consumption ◽  
Lateral Habenula ◽  
Coping Responses ◽  
Axon Terminals ◽  
Motivated Behavior ◽  
Serotonin Neurons ◽  
Motivated Behaviors ◽  
Increased Activity

AbstractThe lateral hypothalamus (LH) plays an important role in motivated behavior. However, it is not known how LH neural outputs dynamically signal to major downstream targets to organize behavior. We used multi-fiber photometry to show that three major LH neural outputs projecting to the dorsal raphe nucleus (DRN), ventral tegmental area (VTA), and lateral habenula (LHb) exhibit significant coherent activity in mice engaging motivated responses, which decrease during immobility. Mice engaging active coping responses exhibit increased activity at LH axon terminals that precedes an increase in the activity of serotonin neurons and dopamine neurons, indicating that they may play a role in initiating active responses stemming from LH signal transmissions. The optogenetic activation of LH axon terminals in either the DRN, VTA, or LHb was sufficient to increase mobility but had different effects on passive avoidance and sucrose consumption, suggesting that LH outputs use complementary mechanisms to control behavioral responses. Our results support the notion that the three LH neural outputs play complementary roles in initiating motivated behaviors.

scholarly journals Supramammillary neurons projecting to the septum regulate dopamine and motivation for environmental interaction in mice

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Andrew J. Kesner ◽  
Rick Shin ◽  
Coleman B. Calva ◽  
Reuben F. Don ◽  
Sue Junn ◽  
...  
Keyword(s):  
Ventral Tegmental Area ◽  
Dopamine Neurons ◽  
Theta Oscillations ◽  
Mesolimbic Dopamine ◽  
Sucrose Consumption ◽  
Behavioral Interaction ◽  
Hypothalamic Structure ◽  
Hippocampal Theta ◽  
Substances Of Abuse ◽  
Stimulation Of

AbstractThe supramammillary region (SuM) is a posterior hypothalamic structure, known to regulate hippocampal theta oscillations and arousal. However, recent studies reported that the stimulation of SuM neurons with neuroactive chemicals, including substances of abuse, is reinforcing. We conducted experiments to elucidate how SuM neurons mediate such effects. Using optogenetics, we found that the excitation of SuM glutamatergic (GLU) neurons was reinforcing in mice; this effect was relayed by their projections to septal GLU neurons. SuM neurons were active during exploration and approach behavior and diminished activity during sucrose consumption. Consistently, inhibition of SuM neurons disrupted approach responses, but not sucrose consumption. Such functions are similar to those of mesolimbic dopamine neurons. Indeed, the stimulation of SuM-to-septum GLU neurons and septum-to-ventral tegmental area (VTA) GLU neurons activated mesolimbic dopamine neurons. We propose that the supramammillo-septo-VTA pathway regulates arousal that reinforces and energizes behavioral interaction with the environment.

scholarly journals Response dynamics of midbrain dopamine neurons and serotonin neurons to heroin, nicotine, cocaine, and MDMA

2018 ◽  
Vol 4 (1) ◽  
Author(s):  
Chao Wei ◽  
Xiao Han ◽  
Danwei Weng ◽  
Qiru Feng ◽  
Xiangbing Qi ◽  
...  
Keyword(s):  
Dopamine Neurons ◽  
Response Dynamics ◽  
Serotonin Neurons ◽  
Midbrain Dopamine ◽  
Midbrain Dopamine Neurons

scholarly journals Multiple Timescales of Memory in Lateral Habenula and Dopamine Neurons

Neuron ◽  
2010 ◽  
Vol 67 (3) ◽  
pp. 499-510 ◽  
Author(s):  
Ethan S. Bromberg-Martin ◽  
Masayuki Matsumoto ◽  
Hiroyuki Nakahara ◽  
Okihide Hikosaka
Keyword(s):  
Dopamine Neurons ◽  
Lateral Habenula ◽  
Multiple Timescales

scholarly journals Functional evidence for a direct excitatory projection from the lateral habenula to the ventral tegmental area in the rat

2016 ◽  
Vol 116 (3) ◽  
pp. 1161-1174 ◽  
Author(s):  
P. Leon Brown ◽  
Paul D. Shepard
Keyword(s):  
Ventral Tegmental Area ◽  
Dopamine Neurons ◽  
Lateral Habenula ◽  
Aversive Stimuli ◽  
Rat Pups ◽  
Tegmental Nucleus ◽  
Fasciculus Retroflexus ◽  
Ventral Tegmental ◽  
Midbrain Dopamine ◽  
Midbrain Dopamine Neurons

The lateral habenula, a phylogenetically conserved epithalamic structure, is activated by aversive stimuli and reward omission. Excitatory efferents from the lateral habenula predominately inhibit midbrain dopamine neuronal firing through a disynaptic, feedforward inhibitory mechanism involving the rostromedial tegmental nucleus. However, the lateral habenula also directly targets dopamine neurons within the ventral tegmental area, suggesting that opposing actions may result from increased lateral habenula activity. In the present study, we tested the effect of habenular efferent stimulation on dopamine and nondopamine neurons in the ventral tegmental area of Sprague-Dawley rats using a parasagittal brain slice preparation. Single pulse stimulation of the fasciculus retroflexus excited 48% of dopamine neurons and 51% of nondopamine neurons in the ventral tegmental area of rat pups. These proportions were not altered by excision of the rostromedial tegmental nucleus and were evident in both cortical- and striatal-projecting dopamine neurons. Glutamate receptor antagonists blocked this excitation, and fasciculus retroflexus stimulation elicited evoked excitatory postsynaptic potentials with a nearly constant onset latency, indicative of a monosynaptic, glutamatergic connection. Comparison of responses in rat pups and young adults showed no significant difference in the proportion of neurons excited by fasciculus retroflexus stimulation. Our data indicate that the well-known, indirect inhibitory effect of lateral habenula activation on midbrain dopamine neurons is complemented by a significant, direct excitatory effect. This pathway may contribute to the role of midbrain dopamine neurons in processing aversive stimuli and salience.

scholarly journals Acute fasting increases somatodendritic dopamine release in the ventral tegmental area

2015 ◽  
Vol 114 (2) ◽  
pp. 1072-1082 ◽  
Author(s):  
Aaron G. Roseberry
Keyword(s):  
Ventral Tegmental Area ◽  
Food Restriction ◽  
Dopamine Release ◽  
Dopamine Neurons ◽  
Dopamine System ◽  
Mesolimbic Dopamine System ◽  
Axon Terminals ◽  
Highly Active ◽  
Target Sites ◽  
Ventral Tegmental

Fasting and food restriction alter the activity of the mesolimbic dopamine system to affect multiple reward-related behaviors. Food restriction decreases baseline dopamine levels in efferent target sites and enhances dopamine release in response to rewards such as food and drugs. In addition to releasing dopamine from axon terminals, dopamine neurons in the ventral tegmental area (VTA) also release dopamine from their soma and dendrites, and this somatodendritic dopamine release acts as an autoinhibitory signal to inhibit neighboring VTA dopamine neurons. It is unknown whether acute fasting also affects dopamine release, including the local inhibitory somatodendritic dopamine release in the VTA. In these studies, I have tested whether fasting affects the inhibitory somatodendritic dopamine release within the VTA by examining whether an acute 24-h fast affects the inhibitory postsynaptic current mediated by evoked somatodendritic dopamine release (D2R IPSC). Fasting increased the contribution of the first action potential to the overall D2R IPSC and increased the ratio of repeated D2R IPSCs evoked at short intervals. Fasting also reduced the effect of forskolin on the D2R IPSC and led to a significantly bigger decrease in the D2R IPSC in low extracellular calcium. Finally, fasting resulted in an increase in the D2R IPSCs when a more physiologically relevant train of D2R IPSCs was used. Taken together, these results indicate that fasting caused a change in the properties of somatodendritic dopamine release, possibly by increasing dopamine release, and that this increased release can be sustained under conditions where dopamine neurons are highly active.

scholarly journals Social and Hydrological Responses to Extreme Precipitations: An Interdisciplinary Strategy for Postflood Investigation

2014 ◽  
Vol 6 (1) ◽  
pp. 135-153 ◽  
Author(s):  
Isabelle Ruin ◽  
Céline Lutoff ◽  
Brice Boudevillain ◽  
Jean-Dominique Creutin ◽  
S. Anquetin ◽  
...  
Keyword(s):  
Large Scale ◽  
Flash Flood ◽  
Interdisciplinary Collaboration ◽  
Behavioral Responses ◽  
Temporal Analysis ◽  
Field Investigation ◽  
Second Step ◽  
Coping Responses ◽  
Factors Influencing ◽  
Hydrometeorological Conditions

Abstract This paper describes and illustrates a methodology to conduct postflood investigations based on interdisciplinary collaboration between social and physical scientists. The method, designed to explore the link between crisis behavioral response and hydrometeorological dynamics, aims at understanding the spatial and temporal capacities and constraints on human behaviors in fast-evolving hydrometeorological conditions. It builds on methods coming from both geosciences and transportations studies to complement existing postflood field investigation methodology used by hydrometeorologists. The authors propose an interview framework, structured around a chronological guideline to allow people who experienced the flood firsthand to tell the stories of the circumstances in which their activities were affected during the flash flood. This paper applies the data collection method to the case of the 15 June 2010 flash flood event that killed 26 people in the Draguignan area (Var, France). As a first step, based on the collected narratives, an abductive approach allowed the identification of the possible factors influencing individual responses to flash floods. As a second step, behavioral responses were classified into categories of activities based on the respondents' narratives. Then, aspatial and temporal analysis of the sequences made of the categories of action to contextualize the set of coping responses with respect to local hydrometeorological conditions is proposed. During this event, the respondents mostly follow the pace of change in their local environmental conditions as the flash flood occurs, official flood anticipation being rather limited and based on a large-scale weather watch. Therefore, contextual factors appear as strongly influencing the individual's ability to cope with the event in such a situation.

scholarly journals Firing patterns of serotonin neurons underlying cognitive flexibility

2016 ◽  
Author(s):  
Sara Matias ◽  
Eran Lottem ◽  
Guillaume P. Dugué ◽  
Zachary F. Mainen
Keyword(s):  
Cognitive Flexibility ◽  
Causal Structure ◽  
Dopamine Neurons ◽  
Prediction Errors ◽  
Firing Patterns ◽  
Learning Rates ◽  
Serotonin Neurons ◽  
Endogenous Role ◽  
Flexible Adaptation

Serotonin is implicated in mood and affective disorders1,2 but growing evidence suggests that its core endogenous role may be to promote flexible adaptation to changes in the causal structure of the environment3–8. This stems from two functions of endogenous serotonin activation: inhibiting learned responses that are not currently adaptive9,10 and driving plasticity to reconfigure them1113. These mirror dual functions of dopamine in invigorating reward-related responses and promoting plasticity that reinforces new ones16,17. However, while dopamine neurons are known to be activated by reward prediction errors18,19, consistent with theories of reinforcement learning, the reported firing patterns of serotonin neurons21–23 do not accord with any existing theories1,24,25. Here, we used long-term photometric recordings in mice to study a genetically-defined population of dorsal raphe serotonin neurons whose activity we could link to normal reversal learning. We found that these neurons are activated by both positive and negative prediction errors, thus reporting the kind of surprise signal proposed to promote learning in conditions of uncertainty26,27. Furthermore, by comparing cue responses of serotonin and dopamine neurons we found differences in learning rates that could explain the importance of serotonin in inhibiting perseverative responding. Together, these findings show how the firing patterns of serotonin neurons support a role in cognitive flexibility and suggest a revised model of dopamine-serotonin opponency with potential clinical implications.

scholarly journals The tubular striatum and nucleus accumbens distinctly represent reward-taking and seeking

2020 ◽  
Author(s):  
Katherine N. Wright ◽  
Daniel W Wesson
Keyword(s):  
Nucleus Accumbens ◽  
Ventral Striatum ◽  
Neural Representation ◽  
Single Unit Activity ◽  
Self Administration ◽  
Reward Seeking ◽  
Motivated Behavior ◽  
Behavioral Paradigm ◽  
Motivated Behaviors ◽  
Goal Directed Behavior

The ventral striatum regulates motivated behaviors which are essential for survival. The ventral striatum contains both the nucleus accumbens (NAc), which is well established to contribute to motivated behavior, and the adjacent tubular striatum (TuS), which is poorly understood in this context. We reasoned that these ventral striatal subregions may be uniquely specialized in their neural representation of goal-directed behavior. To test this, we simultaneously examined TuS and NAc single-unit activity as male mice engaged in a sucrose self-administration task, which included extinction and cue-induced reinstatement sessions. While background levels of activity were comparable between regions, more TuS neurons were recruited upon reward-taking, and among recruited neurons, TuS neurons displayed greater changes in their firing during reward-taking and extinction than those in the NAc. Conversely, NAc neurons displayed greater changes in their firing during cue-reinstated reward-seeking. Interestingly, at least in the context of this behavioral paradigm, TuS neural activity predicted reward-seeking whereas NAc activity did not. Together, by directly comparing their dynamics in several behavioral contexts, this work reveals that the NAc and TuS ventral striatum subregions distinctly represent reward-taking and seeking.

scholarly journals The Emerging Role of LHb CaMKII in the Comorbidity of Depressive and Alcohol Use Disorders

2020 ◽  
Vol 21 (21) ◽  
pp. 8123
Author(s):  
Chaya Shor ◽  
Wanhong Zuo ◽  
Jean D. Eloy ◽  
Jiang-Hong Ye
Keyword(s):  
Alcohol Use ◽  
Depressive Disorders ◽  
Alcohol Use Disorders ◽  
Lateral Habenula ◽  
Calcium Calmodulin Dependent ◽  
Targeted Treatments ◽  
Serotonin Neurons ◽  
Significant Public Health ◽  
Core Components ◽  
Dependent Protein

Depressive disorders and alcohol use disorders are widespread among the general population and are significant public health and economic burdens. Alcohol use disorders often co-occur with other psychiatric conditions and this dual diagnosis is called comorbidity. Depressive disorders invariably contribute to the development and worsening of alcohol use disorders, and vice versa. The mechanisms underlying these disorders and their comorbidities remain unclear. Recently, interest in the lateral habenula, a small epithalamic brain structure, has increased because it becomes hyperactive in depression and alcohol use disorders, and can inhibit dopamine and serotonin neurons in the midbrain reward center, the hypofunction of which is believed to be a critical contributor to the etiology of depressive disorders and alcohol use disorders as well as their comorbidities. Additionally, calcium/calmodulin-dependent protein kinase II (CaMKII) in the lateral habenula has emerged as a critical player in the etiology of these comorbidities. This review analyzes the interplay of CaMKII signaling in the lateral habenula associated with depressive disorders and alcohol use disorders, in addition to the often-comorbid nature of these disorders. Although most of the CaMKII signaling pathway’s core components have been discovered, much remains to be learned about the biochemical events that propagate and link between depression and alcohol abuse. As the field rapidly advances, it is expected that further understanding of the pathology involved will allow for targeted treatments.

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