scholarly journals Dichotomous dopaminergic and noradrenergic neural states mediate distinct aspects of exploitative behavioral states

2021 ◽  
Vol 7 (30) ◽  
pp. eabh2059
Author(s):  
Aaron C. Koralek ◽  
Rui M. Costa
Keyword(s):  
Dopamine Neurons ◽  
Calcium Dynamics ◽  
Noradrenergic Neurons ◽  
Dopaminergic Activity ◽  
Sustained Activity ◽  
Basal Activity ◽  
Behavioral Paradigm ◽  
Behavioral States ◽  
Sustained Inhibition ◽  
Action Choice

The balance between exploiting known actions and exploring alternatives is critical for survival and hypothesized to rely on shifts in neuromodulation. We developed a behavioral paradigm to capture exploitative and exploratory states and imaged calcium dynamics in genetically identified dopaminergic and noradrenergic neurons. During exploitative states, characterized by motivated repetition of the same action choice, dopamine neurons in SNc encoding movement vigor showed sustained elevation of basal activity that lasted many seconds. This sustained activity emerged from longer positive responses, which accumulated during exploitative action-reward bouts, and hysteretic dynamics. Conversely, noradrenergic neurons in LC showed sustained inhibition of basal activity due to the accumulation of longer negative responses in LC. Chemogenetic manipulation of these sustained dynamics revealed that dopaminergic activity mediates action drive, whereas noradrenergic activity modulates choice diversity. These data uncover the emergence of sustained neural states in dopaminergic and noradrenergic networks that mediate dissociable aspects of exploitative bouts.

scholarly journals SUSTAINED DOPAMINERGIC PLATEAUS AND NORADRENERGIC DEPRESSIONS MEDIATE DISSOCIABLE ASPECTS OF EXPLOITATIVE STATES

2019 ◽  
Author(s):  
Aaron C. Koralek ◽  
Rui M. Costa
Keyword(s):  
Dopaminergic Neurons ◽  
Substantia Nigra Pars Compacta ◽  
State Transitions ◽  
Calcium Dynamics ◽  
Noradrenergic Neurons ◽  
Sustained Activity ◽  
Baseline Activity ◽  
Behavioral Paradigm ◽  
Action Choice ◽  
Response Vigor

ABSTRACTWe are constantly faced with the trade-off between exploiting actions with known outcomes and exploring alternative actions whose outcomes may be better. This balance has been hypothesized to rely on dopaminergic neurons of the substantia nigra pars compacta (SNc)1 and noradrenergic neurons of the locus coeruleus (LC)2–3. We developed a behavioral paradigm to capture exploitative and exploratory states, and imaged calcium dynamics in genetically-identified dopaminergic SNc neurons and noradrenergic LC neurons during state transitions. During exploitative states, characterized by motivated repetition of the same action choice, we found dichotomous changes in baseline activity in SNc and LC, with SNc showing higher and LC showing lower sustained activity. These sustained neural states emerged from the accumulation of lengthened positive responses and hysteretic dynamics in SNc networks, and lengthened negative responses in LC. Sustained activity could not be explained by classical reinforcement learning parameters, and in SNc but not LC, emerged in subpopulations coding for response vigor. Manipulating the sustained activity of SNc and LC revealed that dopaminergic activity primarily mediates engagement and motivation, whereas noradrenergic activity modulates action selection. These data uncover the emergence of sustained neural states in dopaminergic and noradrenergic networks that mediate dissociable aspects of exploitative bouts.

scholarly journals Modeling Uncertainty-Seeking Behavior Mediated by Cholinergic Influence on Dopamine

2019 ◽  
Author(s):  
Marwen Belkaid ◽  
Jeffrey L. Krichmar
Keyword(s):  
Decision Making ◽  
Dopaminergic Neurons ◽  
Cholinergic System ◽  
Dopamine Neurons ◽  
Comprehensive Understanding ◽  
Dopaminergic Activity ◽  
Integrate And Fire ◽  
Major Implication ◽  
Seeking Behavior

AbstractRecent findings suggest that acetylcholine mediates uncertainty-seeking behaviors through its projection to dopamine neurons – another neuromodulatory system known for its major implication in reinforcement learning and decision-making. In this paper, we propose a leaky-integrate-and-fire model of this mechanism. It implements a softmax-like selection with an uncertainty bonus by a cholinergic drive to dopaminergic neurons, which in turn influence synaptic currents of downstream neurons. The model is able to reproduce experimental data in two decision-making tasks. It also predicts that i) in the absence of cholinergic input, dopaminergic activity would not correlate with uncertainty, and that ii) the adaptive advantage brought by the implemented uncertainty-seeking mechanism is most useful when sources of reward are not highly uncertain. Moreover, this modeling work allows us to propose novel experiments which might shed new light on the role of acetylcholine in both random and directed exploration. Overall, this study thus contributes to a more comprehensive understanding of the roles of the cholinergic system and its involvement in decision-making in particular.

scholarly journals Power and Coherence in the EEG of the Rat: Impact of Behavioral States, Cortical Area, Lateralization and Light/Dark Phases

2020 ◽  
Vol 2 (4) ◽  
pp. 536-556
Author(s):  
Alejandra Mondino ◽  
Matías Cavelli ◽  
Joaquín González ◽  
Lucía Osorio ◽  
Santiago Castro-Zaballa ◽  
...  
Keyword(s):  
Olfactory Bulb ◽  
Rem Sleep ◽  
Cortical Area ◽  
Spectral Power ◽  
Adult Rats ◽  
Cognitive Capacities ◽  
Cortical Areas ◽  
Basal Activity ◽  
Behavioral States ◽  
Cortical System

The sleep-wake cycle is constituted by three behavioral states: wakefulness (W), non-REM (NREM) and REM sleep. These states are associated with drastic changes in cognitive capacities, mostly determined by the function of the thalamo-cortical system, whose activity can be examined by means of intra-cranial electroencephalogram (iEEG). With the purpose to study in depth the basal activity of the iEEG in adult rats, we analyzed the spectral power and coherence of the iEEG during W and sleep in the paleocortex (olfactory bulb), and in neocortical areas. We also analyzed the laterality of the signals, as well as the influence of the light and dark phases. We found that the iEEG power and coherence of the whole spectrum were largely affected by behavioral states and highly dependent on the cortical areas recorded. We also determined that there are night/day differences in power and coherence during sleep, but not in W. Finally, we observed that, during REM sleep, intra-hemispheric coherence differs between right and left hemispheres. We conclude that the iEEG dynamics are highly dependent on the cortical area and behavioral states. Moreover, there are light/dark phases disparities in the iEEG during sleep, and intra-hemispheric connectivity differs between both hemispheres during REM sleep.

A pair of dopamine neurons mediate chronic stress signals to induce learning deficit in Drosophila melanogaster

2021 ◽  
Vol 118 (42) ◽  
pp. e2023674118
Author(s):  
Jia Jia ◽  
Lei He ◽  
Junfei Yang ◽  
Yichun Shuai ◽  
Jingjing Yang ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Chronic Stress ◽  
Dopaminergic Neurons ◽  
Mushroom Body ◽  
Dopamine Neurons ◽  
Learning Deficit ◽  
Dopaminergic Activity ◽  
Output Neurons ◽  
Stress Signals ◽  
Underlying Mechanisms

Chronic stress could induce severe cognitive impairments. Despite extensive investigations in mammalian models, the underlying mechanisms remain obscure. Here, we show that chronic stress could induce dramatic learning and memory deficits in Drosophila melanogaster. The chronic stress–induced learning deficit (CSLD) is long lasting and associated with other depression-like behaviors. We demonstrated that excessive dopaminergic activity provokes susceptibility to CSLD. Remarkably, a pair of PPL1-γ1pedc dopaminergic neurons that project to the mushroom body (MB) γ1pedc compartment play a key role in regulating susceptibility to CSLD so that stress-induced PPL1-γ1pedc hyperactivity facilitates the development of CSLD. Consistently, the mushroom body output neurons (MBON) of the γ1pedc compartment, MBON-γ1pedc>α/β neurons, are important for modulating susceptibility to CSLD. Imaging studies showed that dopaminergic activity is necessary to provoke the development of chronic stress–induced maladaptations in the MB network. Together, our data support that PPL1-γ1pedc mediates chronic stress signals to drive allostatic maladaptations in the MB network that lead to CSLD.

scholarly journals Stress controllability modulates basal activity of dopamine neurons in the substantia nigra compacta

eNeuro ◽  
2021 ◽  
pp. ENEURO.0044-21.2021
Author(s):  
Li Yao ◽  
Yongfeng Li ◽  
Zhijun Diao ◽  
Yuanyuan Di ◽  
Meilin Wu ◽  
...  
Keyword(s):  
Substantia Nigra ◽  
Dopamine Neurons ◽  
Basal Activity

scholarly journals Power and coherence in the EEG of the rat: impact of behavioral states, cortical area, lateralization and light/dark phases

2020 ◽  
Author(s):  
Alejandra Mondino ◽  
Matías Cavelli ◽  
Joaquín Gonzalez ◽  
Lucía Osorio ◽  
Santiago Castro-Zaballa ◽  
...  
Keyword(s):  
Olfactory Bulb ◽  
Rem Sleep ◽  
Cortical Area ◽  
Spectral Power ◽  
Cortical Activity ◽  
Adult Rats ◽  
Cortical Areas ◽  
Basal Activity ◽  
Behavioral States ◽  
Cortical System

AbstractThe sleep-wake cycle is constituted by three behavioral states: wakefulness (W), non-REM (NREM) and REM sleep. These states are associated with drastic changes in cognitive capacities, mostly determined by the function of the thalamo-cortical system. Thalamo-cortical activity can be examined by means of the intra-cranial electroencephalogram (iEEG).With the purpose to study in depth the basal activity of the iEEG in adult rats, we analyzed the spectral power and coherence of the iEEG during W and sleep in the paleocortex (olfactory bulb), as well as in motor, somatosensory and visual neocortical areas. We also analyzed the laterality (right Vs. left hemispheres) of the signals, as well as the iEEG in function of the light and dark phases.We found that the iEEG power and coherence of the whole spectrum were largely affected by behavioral states and were highly dependent on the cortical areas recorded. We also determined that there are night/day differences in power and coherence during sleep, but not in W. Finally, while we did not find right/left differences in power either in W or sleep, we observed that during REM sleep intra-hemispheric coherence differs between both hemispheres.We conclude that the iEEG dynamics is highly dependent on the cortical area and behavioral states. We also determine that there are light/dark phases disparities in the iEEG that emerge during sleep, and that intra-hemispheric connectivity differs between both hemispheres only during REM sleep.

Calcium Dynamics Underlying Pacemaker-Like and Burst Firing Oscillations in Midbrain Dopaminergic Neurons: A Computational Study

1999 ◽  
Vol 82 (5) ◽  
pp. 2249-2261 ◽  
Author(s):  
B. Amini ◽  
J. W. Clark ◽  
C. C. Canavier
Keyword(s):  
Dopaminergic Neurons ◽  
Computational Study ◽  
Compartment Model ◽  
Burst Firing ◽  
Dopamine Neurons ◽  
Model Parameters ◽  
Calcium Dynamics ◽  
Square Wave ◽  
Wave Oscillation ◽  
Fluid Compartment

A mathematical model of midbrain dopamine neurons has been developed to understand the mechanisms underlying two types of calcium-dependent firing patterns that these cells exhibit in vitro. The first is the regular, pacemaker-like firing exhibited in a slice preparation, and the second is a burst firing pattern sometimes exhibited in the presence of apamin. Because both types of oscillations are blocked by nifedipine, we have focused on the slow calcium dynamics underlying these firing modes. The underlying oscillations in membrane potential are best observed when action potentials are blocked by the application of TTX. This converts the regular single-spike firing mode to a slow oscillatory potential (SOP) and apamin-induced bursting to a slow square-wave oscillation. We hypothesize that the SOP results from the interplay between the L-type calcium current (ICa,L) and the apamin-sensitive calcium-activated potassium current ( I K,Ca,SK). We further hypothesize that the square-wave oscillation results from the alternating voltage activation and calcium inactivation of I Ca,L. Our model consists of two components: a Hodgkin-Huxley-type membrane model and a fluid compartment model. A material balance on Ca2+ is provided in the cytosolic fluid compartment, whereas calcium concentration is considered constant in the extracellular compartment. Model parameters were determined using both voltage-clamp and calcium-imaging data from the literature. In addition to modeling the SOP and square-wave oscillations in dopaminergic neurons, the model provides reasonable mimicry of the experimentally observed response of SOPs to TEA application and elongation of the plateau duration of the square-wave oscillations in response to calcium chelation.

scholarly journals Slowly evolving dopaminergic activity modulates the moment-to-moment probability of reward-related self-timed movements

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Allison E Hamilos ◽  
Giulia Spedicato ◽  
Ye Hong ◽  
Fangmiao Sun ◽  
Yulong Li ◽  
...  
Keyword(s):  
Dopaminergic System ◽  
Movement Time ◽  
Human Movement ◽  
The Self ◽  
Dopamine Neurons ◽  
Movement Initiation ◽  
Dopaminergic Activity ◽  
The Moment ◽  
The Relationship ◽  
Criterion Time

Clues from human movement disorders have long suggested that the neurotransmitter dopamine plays a role in motor control, but how the endogenous dopaminergic system influences movement is unknown. Here we examined the relationship between dopaminergic signaling and the timing of reward-related movements in mice. Animals were trained to initiate licking after a self-timed interval following a start-timing cue; reward was delivered in response to movements initiated after a criterion time. The movement time was variable from trial-to-trial, as expected from previous studies. Surprisingly, dopaminergic signals ramped-up over seconds between the start-timing cue and the self-timed movement, with variable dynamics that predicted the movement/reward time on single trials. Steeply rising signals preceded early lick-initiation, whereas slowly rising signals preceded later initiation. Higher baseline signals also predicted earlier self-timed movements. Optogenetic activation of dopamine neurons during self-timing did not trigger immediate movements, but rather caused systematic early-shifting of movement initiation, whereas inhibition caused late-shifting, as if modulating the probability of movement. Consistent with this view, the dynamics of the endogenous dopaminergic signals quantitatively predicted the moment-by-moment probability of movement initiation on single trials. We propose that ramping dopaminergic signals, likely encoding dynamic reward expectation, can modulate the decision of when to move.

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