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1.  The subthalamic nucleus keeps you high on emotion: behavioral consequences of its inactivation 
The subthalamic nucleus (STN) belongs to the basal ganglia and is the current target for the surgical treatment of neurological and psychiatric disorders such as Parkinson’s Disease (PD) and obsessive compulsive disorders (OCD), but also a proposed site for the treatment of addiction. It is therefore very important to understand its functions in order to anticipate and prevent possible side-effects in the patients. Although the involvement of the STN is well documented in motor, cognitive and motivational processes, less is known regarding emotional processes. Here we have investigated the direct consequences of STN inactivation by excitotoxic lesions on emotional processing and reinforcement in the rat. We have used various behavioral procedures to assess affect for neutral, positive and negative reinforcers in STN lesioned rats. STN lesions reduced affective responses for positive (sweet solutions) and negative (electric foot shock, Lithium Chloride-induced sickness) reinforcers while they had no effect on responses for a more neutral reinforcer (novelty induced place preference (NIPP)). Furthermore, when given the choice between saccharine, a sweet but non caloric solution, and glucose, a more bland but caloric solution, in contrast to sham animals that preferred saccharine, STN lesioned animals preferred glucose over saccharine. Taken altogether these results reveal that STN plays a critical role in emotional processing. These results, in line with some clinical observations in PD patients subjected to STN surgery, suggest possible emotional side-effects of treatments targeting the STN. They also suggest that the increased motivation for sucrose previously reported cannot be due to increased pleasure, but could be responsible for the decreased motivation for cocaine reported after STN inactivation.
PMCID: PMC4257083  PMID: 25538581
basal ganglia; emotion; taste reactivity; conditioned fear; ultrasonic vocalization; conditioned place avoidance; novelty-induced place preference; glucose vs. saccharine choice
2.  Linking reward processing to behavioral output: motor and motivational integration in the primate subthalamic nucleus 
The expectation and detection of motivationally relevant events is a major determinant of goal-directed behavior and there is a strong interest in the contribution of basal ganglia in the integration of motivational processes into behavioral output. Recent research has focused on the role of the subthalamic nucleus (STN) in the motivational control of action, but it remains to be determined how information about reward is encoded in this nucleus. We recorded the activity of single neurons in the STN of two behaving monkeys to examine whether activity was influenced by the delivery of reward in an instrumental task, a Pavlovian stimulus-reward association, or outside of a task context. We confirmed preliminary findings indicating that STN neurons were sensitive not only to rewards obtained during task performance, but also to the expectation of reward when its delivery was delayed in time. Most of the modulations at the onset of reaching movement were combined with modulations following reward delivery, suggesting the convergence of signals related to the animal’s movement and its outcome in the same neurons. Some neurons were also influenced by the visuomotor contingencies of the task, i.e., target location and/or movement direction. In addition, modulations were observed under conditions where reward delivery was not contingent on an instrumental response, even in the absence of a reward predictive cue. Taken as a whole, these results demonstrate a potential contribution of the STN to motivational control of behavior in the non-human primate, although problems in distinguishing neuronal signals related to reward from those related to motor behavior should be considered. Characterizing the specificity of reward processing in the STN remains challenging and could have important implications for understanding the influence of this key component of basal ganglia circuitry on emotional and motivated behaviors under normal and pathological conditions.
PMCID: PMC3865598  PMID: 24381555
basal ganglia; reinforcement; reward expectation; context processing; single-neuron activity; monkey
3.  Frontal Cortex-Like Functions of the Subthalamic Nucleus 
The subthalamic nucleus (STN) has been considered a motor structure for a long time. Over the last 20 years, anatomical and behavioral data have highlighted the position of the STN within a prefrontal-associative and a limbic loops, suggesting that the STN should play a critical role in frontal functions such as attention, inhibitory control (including impulsive action, compulsivity, impulsive choice), and motivation. Here we will review the work highlighting these functions of the STN.
PMCID: PMC3190186  PMID: 22013416
basal ganglia; subthalamic nucleus; deep brain stimulation; attention; motivation; impulsivity; compulsion; behavioral inhibition
4.  Is there an inhibitory-response-control system in the rat? Evidence from anatomical and pharmacological studies of behavioral inhibition 
Many common psychiatric conditions, such as attention deficit/hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), Parkinson's disease, addiction and pathological gambling are linked by a failure in the mechanisms that control, or inhibit, inappropriate behavior. Models of rat behavioral inhibition permit us to study in detail the anatomical and pharmacological bases of inhibitory failure, using methods that translate directly with patient assessment in the clinic. This review updates current ideas relating to behavioral inhibition based on two significant lines of evidence from rat studies:
(1) To integrate new findings from the stop-signal task into existing models of behavioral inhibition, in particular relating to ‘impulsive action’ control. The stop-signal task has been used for a number of years to evaluate psychiatric conditions and has recently been translated for use in the rat, bringing a wealth of new information to behavioral inhibition research.
(2) To consider the importance of the subthalamic nucleus (STN) in the neural circuitry of behavioral inhibition. This function of this nucleus is central to a number of ‘disinhibitory’ disorders such as Parkinson's disease and OCD, and their therapies, but its role in behavioral inhibition is still undervalued, and often not considered in preclinical models of behavioral control.
Integration of these findings has pinpointed the orbitofrontal cortex (OF), dorsomedial striatum (DMStr) and STN within a network that normally inhibits many forms of behavior, including both impulsive and compulsive forms. However, there are distinct differences between behavioral subtypes in their neurochemical modulation.
This review brings new light to the classical view of the mechanisms that inhibit behavior, in particular suggesting a far more prominent role for the STN, a structure that is usually omitted from conventional behavioral-inhibition networks. The OF–DMStr–STN circuitry may form the basis of a control network that defines behavioral inhibition and that acts to suppress or countermand many forms of inappropriate or maladaptive behavior.
PMCID: PMC2789250  PMID: 19615404
Dopamine; Serotonin; Noradrenaline; Atomoxetine; Orbitofrontal; Subthalamic nucleus; Dorsomedial striatum; Nucleus accumbens; SSRT; Premature response; Perseverative response
5.  Bilateral high-frequency stimulation of the subthalamic nucleus on attentional performance: transient deleterious effects and enhanced motivation in both intact and parkinsonian rats 
The European journal of neuroscience  2007;25(4):1187-1194.
It is now well established that subthalamic nucleus high-frequency stimulation (STN HFS) alleviates motor problems in Parkinson's disease. However, its efficacy for cognitive function remains a matter of debate. The aim of this study was to assess the effects of STN HFS in rats performing a visual attentional task. Bilateral STN HFS was applied in intact and in bilaterally dopamine (DA)-depleted rats. In all animals, STN HFS had a transient debilitating effect on all the variables measured in the task. In DA-depleted rats, STN HFS did not alleviate the deficits induced by the DA lesion such as omissions and latency to make correct responses, but induced perseverative approaches to the food magazine, an indicator of enhanced motivation. In sham-operated controls, STN HFS significantly reduced accuracy and induced perseverative behaviour, mimicking partially the effects of bilateral STN lesions in the same task. These results are in line with the hypothesis that STN HFS only partially mimics inactivation of STN produced by lesioning and confirm the motivational exacerbation induced by STN inactivation.
PMCID: PMC1877866  PMID: 17331214
basal ganglia; cognitive functions; deep brain stimulation; dopamine

Results 1-5 (5)