Goal-directed Action Selection Research Articles

Differential effects of acute and prolonged morphine withdrawal on motivational and goal-directed control over reward-seeking behaviour.

Opioid addiction is a relapsing disorder marked by uncontrolled drug use and reduced interest in normally rewarding activities. The current study investigated the impact of spontaneous withdrawal from chronic morphine exposure on emotional, motivational and cognitive processes involved in regulating the pursuit and consumption of food rewards in male rats. In Experiment 1, rats experiencing acute morphine withdrawal lost weight and displayed somatic signs of drug dependence. However, hedonically driven sucrose consumption was significantly elevated, suggesting intact and potentially heightened reward processing. In Experiment 2, rats undergoing acute morphine withdrawal displayed reduced motivation when performing an effortful response for palatable food reward. Subsequent reward devaluation testing revealed that acute withdrawal disrupted their ability to exert flexible goal-directed control over reward seeking. Specifically, morphine-withdrawn rats were impaired in using current reward value to select actions both when relying on prior action-outcome learning and when given direct feedback about the consequences of their actions. In Experiment 3, rats tested after prolonged morphine withdrawal displayed heightened rather than diminished motivation for food rewards and retained their ability to engage in flexible goal-directed action selection. However, brief re-exposure to morphine was sufficient to impair motivation and disrupt goal-directed action selection, though in this case, rats were only impaired in using reward value to select actions in the presence of morphine-paired context cues and in the absence of response-contingent feedback. We suggest that these opioid-withdrawal induced deficits in motivation and goal-directed control may contribute to addiction by interfering with the pursuit of adaptive alternatives to drug use.

Precise and Pervasive Phasic Bursting in Locus Coeruleus during Maternal Behavior in Mice.

The noradrenergic locus coeruleus (LC) mediates key aspects of arousal, memory, and cognition in structured tasks, but its contribution to naturalistic behavior remains unclear. LC activity is thought to multiplex distinct signals by superimposing sustained ("tonic") firing patterns reflecting global brain states, such as arousal and anxiety, and rapidly fluctuating ("phasic") bursts signaling discrete behaviorally significant events. Manipulations of the LC noradrenergic system broadly impair social behavior, but the temporal structure of LC firing and its relationship to social interaction is unknown. One possibility is that tonic firing may increase in the presence of social partners; it is also possible that phasic bursts may accompany specific social events. We used chronic in vivo electrophysiology and fiber photometry to measure single-unit and population neural activity in LC of freely behaving mice during their interactions with pups. We find that pup retrieval elicits remarkably precise phasic activity in LC that cannot be attributed merely to sensory stimuli, motor activity, or reward. Correlation of LC activity with retrieval events shows that phasic events are most closely related to specific subsequent behaviors. The reliability and magnitude of phasic responses strongly suggest that these events are coordinated across LC and broadcast noradrenaline (NA) release throughout the brain. We also observed slow changes in tonic firing when females performed distinct maternal behaviors such as nest building and pup grooming. We therefore propose that LC signals state changes during sustained interactions and contributes to goal-directed action selection during social behavior with globally broadcast NA release.SIGNIFICANCE STATEMENT Locus coeruleus (LC) releases noradrenaline (NA) brain wide, influencing many cognitive, emotional, and physiological processes. Multifunctionality of LC is maintained by multiplexing NA signaling via brief "phasic" patterns of bursting and slowly changing "tonic" firing. Manipulations of NA impair social behavior, yet the structure of LC activity with respect to specific social events is unknown. We measured LC activity in mice freely interacting with pups. We find that pup retrieval elicits precisely timed and pervasive phasic activation of LC that anticipates specific behaviors. We also found that LC neurons exhibited slow fluctuations in firing during sustained behaviors. We propose that LC simultaneously contributes to goal-directed social action selection with globally broadcast NA release and signals social state changes with increased tonic firing.

Parafascicular Thalamic and Orbitofrontal Cortical Inputs to Striatum Represent States for Goal-Directed Action Selection.

Several lines of evidence accrued over the last 5–10 years have converged to suggest that the parafascicular nucleus of the thalamus and the lateral orbitofrontal cortex each represent or contribute to internal state/context representations that guide action selection in partially observable task situations. In rodents, inactivations of each structure have been found to selectively impair performance in paradigms testing goal-directed action selection, but only when that action selection relies on state representations. Electrophysiological evidence has suggested that each structure achieves this function via inputs onto cholinergic interneurons (CINs) in the dorsomedial striatum. Here, we briefly review these studies, then point to anatomical evidence regarding the afferents of each structure and what they suggest about the specific features that each contribute to internal state representations. Finally, we speculate as to whether this role might be achieved interdependently through direct PF→OFC projections, or through the convergence of independent direct orbitofrontal cortex (OFC) and parafascicular nucleus of the thalamus (PF) inputs onto striatal targets.

Affective Experience and Evidence for Animal Consciousness

Affective experience in nonhuman animals is of great interest for both theoretical and practical reasons. This paper highlights research by the psychologists Anthony Dickinson and Bernard Balleine which provides particularly good evidence of conscious affective experience in rats. This evidence is compelling because it implicates a sophisticated system for goal-directed action selection, and demonstrates a contrast between apparently conscious and unconscious evaluative representations with similar content. Meanwhile, the evidence provided by some well-known studies on pain in nonhuman animals is much less convincing. This comparison may offer lessons for the future study of animal consciousness.

Chapter 17 - Computational models of motivated frontal function

Computational models of frontal function have made important contributions to understanding how the frontal lobes support a wide range of important functions, in their interactions with other brain areas including, critically, the basal ganglia (BG). We focus here on the specific case of how different frontal areas support goal-directed, motivated decision-making, by representing three essential types of information: possible plans of action (in more dorsal and lateral frontal areas), affectively significant outcomes of those action plans (in ventral, medial frontal areas including the orbital frontal cortex), and the overall utility of a given plan compared to other possible courses of action (in anterior cingulate cortex). Computational models of goal-directed action selection at multiple different levels of analysis provide insight into the nature of learning and processing in these areas and the relative contributions of the frontal cortex versus the BG. The most common neurologic disorders implicate these areas, and understanding their precise function and modes of dysfunction can contribute to the new field of computational psychiatry, within the broader field of computational neuroscience.

Chronic alcohol exposure disrupts top-down control over basal ganglia action selection to produce habits

Addiction involves a predominance of habitual control mediated through action selection processes in dorsal striatum. Research has largely focused on neural mechanisms mediating a proposed progression from ventral to dorsal lateral striatal control in addiction. However, over reliance on habit striatal processes may also arise from reduced cortical input to striatum, thereby disrupting executive control over action selection. Here, we identify novel mechanisms through which chronic intermittent ethanol exposure and withdrawal (CIE) disrupts top-down control over goal-directed action selection processes to produce habits. We find CIE results in decreased excitability of orbital frontal cortex (OFC) excitatory circuits supporting goal-directed control, and, strikingly, selectively reduces OFC output to the direct output pathway in dorsal medial striatum. Increasing the activity of OFC circuits restores goal-directed control in CIE-exposed mice. Our findings show habitual control in alcohol dependence can arise through disrupted communication between top-down, goal-directed processes onto basal ganglia pathways controlling action selection.

Regulation of actions and habits by ventral hippocampal trkB and adolescent corticosteroid exposure.

In humans and rodents, stress promotes habit-based behaviors that can interfere with action–outcome decision-making. Further, developmental stressor exposure confers long-term habit biases across rodent–primate species. Despite these homologies, mechanisms remain unclear. We first report that exposure to the primary glucocorticoid corticosterone (CORT) in adolescent mice recapitulates multiple neurobehavioral consequences of stressor exposure, including long-lasting biases towards habit-based responding in a food-reinforced operant conditioning task. In both adolescents and adults, CORT also caused a shift in the balance between full-length tyrosine kinase receptor B (trkB) and a truncated form of this neurotrophin receptor, favoring the inactive form throughout multiple corticolimbic brain regions. In adolescents, phosphorylation of the trkB substrate extracellular signal-regulated kinase 42/44 (ERK42/44) in the ventral hippocampus was also diminished, a long-term effect that persisted for at least 12 wk. Administration of the trkB agonist 7,8-dihydroxyflavone (7,8-DHF) during adolescence at doses that stimulated ERK42/44 corrected long-lasting corticosterone-induced behavioral abnormalities. Meanwhile, viral-mediated overexpression of truncated trkB in the ventral hippocampus reduced local ERK42/44 phosphorylation and was sufficient to induce habit-based and depression-like behaviors. Together, our findings indicate that ventral hippocampal trkB is essential to goal-directed action selection, countering habit-based behavior otherwise facilitated by developmental stress hormone exposure. They also reveal an early-life sensitive period during which trkB–ERK42/44 tone determines long-term behavioral outcomes.

Distinct Functions of the Primate Putamen Direct and Indirect Pathways in Adaptive Outcome-Based Action Selection.

Cortico-basal ganglia circuits are critical regulators of reward-based decision making. Reinforcement learning models posit that action reward value is encoded by the firing activity of striatal medium spiny neurons (MSNs) and updated upon changing reinforcement contingencies by dopamine (DA) signaling to these neurons. However, it remains unclear how the anatomically distinct direct and indirect pathways through the basal ganglia are involved in updating action reward value under changing contingencies. MSNs of the direct pathway predominantly express DA D1 receptors and those of the indirect pathway predominantly D2 receptors, so we tested for distinct functions in behavioral adaptation by injecting D1 and D2 receptor antagonists into the putamen of two macaque monkeys performing a free choice task for probabilistic reward. In this task, monkeys turned a handle toward either a left or right target depending on an asymmetrically assigned probability of large reward. Reward probabilities of left and right targets changed after 30–150 trials, so the monkeys were required to learn the higher-value target choice based on action–outcome history. In the control condition, the monkeys showed stable selection of the higher-value target (that more likely to yield large reward) and kept choosing the higher-value target regardless of less frequent small reward outcomes. The monkeys also made flexible changes of selection away from the high-value target when two or three small reward outcomes occurred randomly in succession. DA D1 antagonist injection significantly increased the probability of the monkey switching to the alternate target in response to successive small reward outcomes. Conversely, D2 antagonist injection significantly decreased the switching probability. These results suggest distinct functions of D1 and D2 receptor-mediated signaling processes in action selection based on action–outcome history, with D1 receptor-mediated signaling promoting the stable choice of higher-value targets and D2 receptor-mediated signaling promoting a switch in action away from small reward outcomes. Therefore, direct and indirect pathways appear to have complementary functions in maintaining optimal goal-directed action selection and updating action value, which are dependent on D1 and D2 DA receptor signaling.

Neural determinants of human goal-directed vs. habitual action control and their relation to trait motivation

Instrumental learning is mediated by goal-directed and habit systems in the brain. While rodent studies implicate distinct prefrontal/striatal regions in goal-directed and habit learning, neural systems underpinning these two processes in humans remain poorly understood. Here, using a validated discrimination learning task that distinguishes goal-directed learning from habit learning in 72 subjects in fMRI, we investigated the corticostriatal correlates of goal-directed learning and tested whether brain activation during learning is associated with trait motivation and behavioral performance in the post-learning test phase. Participants showed enhanced activation in medial prefrontal and posterior cingulate cortices during goal-directed action selection in the training phase, whereas habitual action selection activated bilateral insula, bilateral dorsal caudate and left precentral gyrus. In addition, early phase of learning was associated with increased activation in the frontoparietal control network and dorsal striatum, whereas default mode regions depicted increased activation in the late phase. Finally, avoidance motivation scores measured by Behavioral Inhibition/Activation System (BIS/BAS) correlated with accuracy during goal-directed learning and showed a nominally significant correlation with activation in dorsomedial prefrontal cortex during goal-directed acquisition of stimuli. These findings reveal the temporal dynamics of instrumental behavior and suggest that avoidance motivation predicts performance and brain activity during goal-directed learning.

Thalamic Control of Dorsomedial Striatum Regulates Internal State to Guide Goal-Directed Action Selection.

We (Bradfield et al., 2013) have demonstrated previously that parafascicular thalamic nucleus (PF)-controlled neurons in the posterior dorsomedial striatum (pDMS) are critical for interlacing new and existing action-outcome contingencies to control goal-directed action. Based on these findings, it was suggested that animals with a dysfunctional PF-pDMS pathway might suffer a deficit in creating or retrieving internal contexts or "states" on which such information could become conditional. To assess this hypothesis more directly, rats were given a disconnection treatment using contralateral cytotoxic lesions of the PF and pDMS (Group CONTRA) or ipsilateral control lesions (Group IPSI) and trained to press a right and left lever for sucrose and pellet outcomes, after which these contingencies were reversed. The rats were then given an outcome devaluation test (all experiments) and a test of outcome-specific reinstatement (Experiments 1 and 3). We found that devaluation performance was intact for both groups after training of initial contingencies, but impaired for Group CONTRA after reversal. However, performance was restored by additional reversal training. Furthermore, when tested a second time after reversal training, rats in both groups demonstrated responding in accordance with the original contingencies, providing direct evidence of modulation of action selection by state. Finally, we found that external context could substitute for internal state and so could rescue responding in Group CONTRA, but only in the reinstatement test. Together, these findings suggest that animals use internal state information to guide action selection and that this information is modulated by the PF-pDMS pathway.SIGNIFICANCE STATEMENT Individuals with Parkinson's disease dementia often suffer a characteristic deficit in "cognitive flexibility." It has been suggested that neurodegeneration in the pathway between the centromedian/parafascicular thalalmic nucleus (PF) and striatum might underlie such deficits (Smith et al., 2014). In rats, we have similarly observed that a functional disconnection of the PF-posterior dorsomedial striatal pathway produces a specific impairment in the ability to alter goal-directed actions (Bradfield et al., 2013). It was suggested that this impairment could be a result of a deficit in state modulation. Here, we present four experiments that provide evidence for this hypothesis and suggest several ways (e.g., extended practice, providing external cues) in which this state modulation can be rescued.

Reward Sensitivity Enhances Ventrolateral Prefrontal Cortex Activation during Free Choice.

Expressing one's preference via choice can be rewarding, particularly when decisions are voluntarily made as opposed to being forced. An open question is whether engaging in choices involving rewards recruits distinct neural systems as a function of sensitivity to reward. Reward sensitivity is a trait partly influenced by the mesolimbic dopamine system, which can impact an individual's neural and behavioral response to reward cues. Here, we investigated how reward sensitivity contributes to neural activity associated with free and forced choices. Participants underwent a simple decision-making task, which presented free- or forced-choice trials in the scanner. Each trial presented two cues (i.e., points or information) that led to monetary reward at the end of the task. In free-choice trials, participants were offered the opportunity to choose between different reward cues (e.g., points vs. information), whereas forced-choice trials forced individuals to choose within a given reward cue (e.g., information vs. information, or points vs. points). We found enhanced ventrolateral prefrontal cortex (VLPFC) activation during free choice compared to forced choice in individuals with high reward sensitivity scores. Next, using the VLPFC as a seed, we conducted a PPI analysis to identify brain regions that enhance connectivity with the VLPFC during free choice. Our PPI analyses on free vs. forced choice revealed increased VLPFC connectivity with the posterior cingulate and precentral gyrus in reward sensitive individuals. These findings suggest reward sensitivity may recruit attentional control processes during free choice potentially supporting goal-directed behavior and action selection.

A Closer Look at the Effects of Repeated Cocaine Exposure on Adaptive Decision-Making under Conditions That Promote Goal-Directed Control.

It has been proposed that compulsive drug seeking reflects an underlying dysregulation in adaptive behavior that favors habitual (automatic and inflexible) over goal-directed (deliberative and highly flexible) action selection. Rodent studies have established that repeated exposure to cocaine or amphetamine facilitates the development of habits, producing behavior that becomes unusually insensitive to a reduction in the value of its outcome. The current study more directly investigated the effects of cocaine pre-exposure on goal-directed learning and action selection using an approach that discourages habitual performance. After undergoing a 15-day series of cocaine (15 or 30 mg/kg, i.p.) or saline injections and a drug withdrawal period, rats were trained to perform two different lever-press actions for distinct reward options. During a subsequent outcome devaluation test, both cocaine- and saline-treated rats showed a robust bias in their choice between the two actions, preferring whichever action had been trained with the reward that retained its value. Thus, it appears that the tendency for repeated cocaine exposure to promote habit formation does not extend to a more complex behavioral scenario that encourages goal-directed control. To further explore this issue, we assessed how prior cocaine treatment would affect the rats’ ability to learn about a selective reduction in the predictive relationship between one of the two actions and its outcome, which is another fundamental feature of goal-directed behavior. Interestingly, we found that cocaine-treated rats showed enhanced, rather than diminished, sensitivity to this action–outcome contingency degradation manipulation. Given their mutual dependence on striatal dopamine signaling, we suggest that cocaine’s effects on habit formation and contingency learning may stem from a common adaptation in this neurochemical system.

Goal-Directed Decision Making with Spiking Neurons.

Behavioral and neuroscientific data on reward-based decision making point to a fundamental distinction between habitual and goal-directed action selection. The formation of habits, which requires simple updating of cached values, has been studied in great detail, and the reward prediction error theory of dopamine function has enjoyed prominent success in accounting for its neural bases. In contrast, the neural circuit mechanisms of goal-directed decision making, requiring extended iterative computations to estimate values online, are still unknown. Here we present a spiking neural network that provably solves the difficult online value estimation problem underlying goal-directed decision making in a near-optimal way and reproduces behavioral as well as neurophysiological experimental data on tasks ranging from simple binary choice to sequential decision making. Our model uses local plasticity rules to learn the synaptic weights of a simple neural network to achieve optimal performance and solves one-step decision-making tasks, commonly considered in neuroeconomics, as well as more challenging sequential decision-making tasks within 1 s. These decision times, and their parametric dependence on task parameters, as well as the final choice probabilities match behavioral data, whereas the evolution of neural activities in the network closely mimics neural responses recorded in frontal cortices during the execution of such tasks. Our theory provides a principled framework to understand the neural underpinning of goal-directed decision making and makes novel predictions for sequential decision-making tasks with multiple rewards.SIGNIFICANCE STATEMENT Goal-directed actions requiring prospective planning pervade decision making, but their circuit-level mechanisms remain elusive. We show how a model circuit of biologically realistic spiking neurons can solve this computationally challenging problem in a novel way. The synaptic weights of our network can be learned using local plasticity rules such that its dynamics devise a near-optimal plan of action. By systematically comparing our model results to experimental data, we show that it reproduces behavioral decision times and choice probabilities as well as neural responses in a rich set of tasks. Our results thus offer the first biologically realistic account for complex goal-directed decision making at a computational, algorithmic, and implementational level.

Connections of the Mouse Orbitofrontal Cortex and Regulation of Goal-Directed Action Selection by Brain-Derived Neurotrophic Factor

BackgroundDistinguishing between actions that are more likely or less likely to be rewarded is a critical aspect of goal-directed decision making. However, neuroanatomic and molecular mechanisms are not fully understood. MethodsWe used anterograde tracing, viral-mediated gene silencing, functional disconnection strategies, pharmacologic rescue, and designer receptors exclusively activated by designer drugs (DREADDs) to determine the anatomic and functional connectivity between the orbitofrontal cortex (OFC) and the amygdala in mice. In particular, we knocked down brain-derived neurotrophic factor (Bdnf) bilaterally in the OFC or generated an OFC-amygdala “disconnection” by pairing unilateral OFC Bdnf knockdown with lesions of the contralateral amygdala. We characterized decision-making strategies using a task in which mice selected actions based on the likelihood that they would be reinforced. Additionally, we assessed the effects of DREADD-mediated OFC inhibition on the consolidation of action-outcome conditioning. ResultsAs in other species, the OFC projects to the basolateral amygdala and dorsal striatum in mice. Bilateral Bdnf knockdown within the ventrolateral OFC and unilateral Bdnf knockdown accompanied by lesions of the contralateral amygdala impede goal-directed response selection, implicating BDNF-expressing OFC projection neurons in selecting actions based on their consequences. The tyrosine receptor kinase B agonist 7,8-dihydroxyflavone rescues action selection and increases dendritic spine density on excitatory neurons in the OFC. Rho-kinase inhibition also rescues goal-directed response strategies, linking neural remodeling with outcome-based decision making. Finally, DREADD-mediated OFC inhibition weakens new action-outcome memory. ConclusionsActivity-dependent and BDNF-dependent neuroplasticity within the OFC coordinate outcome-based decision making through interactions with the amygdala. These interactions break reward-seeking habits, a putative factor in multiple psychopathologies.

The influence of goals on sense of control.

We examined the influence of goals on sense of control relative to that experienced when taking action randomly. In the experimental task, participants controlled the direction of a moving dot by pressing the left and right keys at will without a specific goal (the control condition), directed the moving dot to a destination as often as possible (the strong goal condition), or kept the moving dot in the central area of the screen (the weak goal condition) for as long as possible. The results showed that the strong goal impaired the sense of control, but the weak goal did not exert an influence. We concluded that the goal-based expectation influenced sense of control, but the goal-directed action selection did not. Furthermore, we proposed a modified comparator model of the sense of control, offering a promising approach to integration of the predictive and postdictive processes involved in the sense of control.

Differentiating neural systems mediating the acquisition vs. expression of goal-directed and habitual behavioral control.

Considerable behavioral data indicate that operant actions can become habitual, as demonstrated by insensitivity to changes in the action-outcome contingency and in subjective outcome values. Notably, although several studies have investigated the neural substrates of habits, none has clearly differentiated the areas of the human brain that support habit formation from those that implement habitual control. We scanned participants with functional magnetic resonance imaging as they learned and performed an operant task in which the conditional structure of the environment encouraged either goal-directed encoding of the consequences of actions, or a habit-like mapping of actions to antecedent cues. Participants were also scanned during a subsequent assessment of insensitivity to outcome devaluation. We identified dissociable roles of the cerebellum and ventral striatum, across learning and test performance, in behavioral insensitivity to outcome devaluation. We also showed that the inferior parietal lobule (an area previously implicated in several aspects of goal-directed action selection, including the attribution of intent and awareness of agency) predicted sensitivity to outcome devaluation. Finally, we revealed a potential functional homology between the human subgenual cortex and rodent infralimbic cortex in the implementation of habitual control. In summary, our findings suggested a broad systems division, at the cortical and subcortical levels, between brain areas mediating the encoding and expression of action-outcome and stimulus-response associations.

Characterizing the associative content of brain structures involved in habitual and goal-directed actions in humans: a multivariate FMRI study.

While there is accumulating evidence for the existence of distinct neural systems supporting goal-directed and habitual action selection in the mammalian brain, much less is known about the nature of the information being processed in these different brain regions. Associative learning theory predicts that brain systems involved in habitual control, such as the dorsolateral striatum, should contain stimulus and response information only, but not outcome information, while regions involved in goal-directed action, such as ventromedial and dorsolateral prefrontal cortex and dorsomedial striatum, should be involved in processing information about outcomes as well as stimuli and responses. To test this prediction, human participants underwent fMRI while engaging in a binary choice task designed to enable the separate identification of these different representations with a multivariate classification analysis approach. Consistent with our predictions, the dorsolateral striatum contained information about responses but not outcomes at the time of an initial stimulus, while the regions implicated in goal-directed action selection contained information about both responses and outcomes. These findings suggest that differential contributions of these regions to habitual and goal-directed behavioral control may depend in part on basic differences in the type of information that these regions have access to at the time of decision making.

Striatopallidal NMDA-receptors control locomotor and conditioning behaviours.

Event Abstract Back to Event Striatopallidal NMDA-receptors control locomotor and conditioning behaviours. Laurie Lambot1*, Elena Chaves Rodriguez1, Yuqing Li2, Serge N. Schiffmann1, Alban De Kerchove D’Exaerde1 and David Gall1 1 Université Libre de Bruxelles, Faculté de Médecine, Belgium 2 University of Florida, College of Medicine, Department of Neurology, United States The basal ganglia (BG) are composed of several interconnected nuclei that have a critical role in goal-directed action selection, motor control, and habits. The striatum, the major input site of the BG, is predominantly composed of medium spiny neurons (MSN), which give rise to two projection circuits originating from two distinct populations of MSN: the striatonigral MSN (dMSN) give rise to the direct pathway and the striatopallidal MSN (iMSN) to the indirect pathway. Balanced activity between both pathways is crucial for harmonious functions of the BG. Imbalance of those two neuronal subpopulations is implicated in major neuropsychiatric disorders such as Parkinson and Huntington diseases as well as drug addiction. Despite the increasing knowledge concerning the key role of the striatal glutamate NMDA receptor (NMDA-R) for the BG physiology, it is still challenging to understand the specific functions of striatopallidal neuron NMDA-R. In this study, by a conditional deletion of the essential GluN1 subunit of NMDA-R specificaly in striatopallidal neurons (cKO), the functions of the NMDA-R in the indirect pathway were adressed. At the cellular level, the deletion of GluN1 in iMSN leads to the reduced number and strength of the excitatory corticostriatopalidal synapses and the intrinsic electro-responsiveness of the iMSN was higher, reflecting an homeostatic adaptation partially compensating the reduced synaptic inputs. The behavioral consequence of the NMDA-R absence in iMSN is an aberrant action selection in goal directed behaviour, without alteration of motor learning but changing of motor strategy, as well as alteration in habituation and amphetamine locomotor sensitization. Taken together, these data indicate that the loss of NMDA-R in the striatopallidal neurons disrupts operant and habituation behaviours. Acknowledgements L.L. was supported by a FRIA (Fonds pour la formation à la Recherche dans l'Industrie et dans l'Agriculture) PhD fellowship from the Fund for Scientific Research-Fonds de la Recherche Scientifique (FRS-FNRS) (Belgium) and Van Buuren grant from the fonds David et Alice Van Buuren. This study was supported by the Fondation Médicale Reine Elisabeth (Belgium). We would like to acknowledge Dr Frédéric Bollet-Quivogne of the Light Microscopy Facility (LiMiF). Keywords: NMDA receptor, Neuronal morphology, Striatum, goal-directed behavior, Synaptic Transmission Conference: 11th National Congress of the Belgian Society for Neuroscience, Mons, Belgium, 22 May - 22 May, 2015. Presentation Type: Oral or Poster presentation Topic: Neuroscience Citation: Lambot L, Chaves Rodriguez E, Li Y, Schiffmann SN, De Kerchove D’Exaerde A and Gall D (2015). Striatopallidal NMDA-receptors control locomotor and conditioning behaviours.. Front. Neurosci. Conference Abstract: 11th National Congress of the Belgian Society for Neuroscience. doi: 10.3389/conf.fnins.2015.89.00074 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 30 Apr 2015; Published Online: 05 May 2015. * Correspondence: Miss. Laurie Lambot, Université Libre de Bruxelles, Faculté de Médecine, Bruxelles, 1070, Belgium, laurie.s.lambot@gmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Laurie Lambot Elena Chaves Rodriguez Yuqing Li Serge N Schiffmann Alban De Kerchove D’Exaerde David Gall Google Laurie Lambot Elena Chaves Rodriguez Yuqing Li Serge N Schiffmann Alban De Kerchove D’Exaerde David Gall Google Scholar Laurie Lambot Elena Chaves Rodriguez Yuqing Li Serge N Schiffmann Alban De Kerchove D’Exaerde David Gall PubMed Laurie Lambot Elena Chaves Rodriguez Yuqing Li Serge N Schiffmann Alban De Kerchove D’Exaerde David Gall Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Multiple Systems for the Motivational Control of Behavior and Associated Neural Substrates in Humans.

In this chapter, we will review evidence about the role of multiple distinct systems in driving the motivation to perform actions in humans. Specifically, we will consider the contribution of goal-directed action selection mechanisms, habitual action selection mechanisms and the influence of Pavlovian predictors on instrumental action selection. We will further evaluate evidence for the contribution of multiple brain areas including ventral frontal and dorsal cortical areas and several distinct parts of the striatum in these processes. Furthermore, we will consider circumstances in which adverse interactions between these systems can result in the decoupling of motivation from incentive valuation and performance.

GABAAα1-mediated plasticity in the orbitofrontal cortex regulates context-dependent action selection.

An essential aspect of goal-directed action selection is differentiating between behaviors that are more, or less, likely to be reinforced. Habits, by contrast, are stimulus-elicited behaviors insensitive to action-outcome contingencies and are considered an etiological factor in several neuropsychiatric disorders. Thus, isolating the neuroanatomy and neurobiology of goal-directed action selection on the one hand, and habit formation on the other, is critical. Using in vivo viral-mediated gene silencing, we knocked down Gabra1 in the orbitofrontal prefrontal cortex (oPFC) in mice, decreasing oPFC GABAAα1 expression, as well as expression of the synaptic marker PSD-95. Mice expressing Green Fluorescent Protein or Gabra1 knockdown in the adjacent M2 motor cortex served as comparison groups. Using instrumental response training followed by action-outcome contingency degradation, we then found that oPFC GABAAα1 deficiency impaired animals' ability to differentiate between actions that were more or less likely to be reinforced, though sensitivity to outcome devaluation and extinction were intact. Meanwhile, M2 GABAAα1 deficiency enhanced sensitivity to action-outcome relationships. Behavioral abnormalities following oPFC GABAAα1 knockdown were rescued by testing mice in a distinct context relative to that in which they had been initially trained. Together, our findings corroborate evidence that chronic GABAAα1 deficiency remodels cortical synapses and suggest that neuroplasticity within the healthy oPFC gates the influence of reward-related contextual stimuli. These stimuli might otherwise promote maladaptive habit-based behavioral response strategies that contribute to-or exacerbate-neuropsychiatric illness.