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

The subthalamic nucleus keeps you high on emotion: behavioral consequences of its inactivation

International audienceThe 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

A few examples of the contribution of animal research in rodents for clinical application of deep brain stimulation

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Alcohol preference influences the subthalamic nucleus control on motivation for alcohol in rats

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La chirurgie au secours des addictions

Initialement développée pour le traitement de pathologies neurologiques, comme la maladie de Parkinson, la stimulation cérébrale profonde est actuellement utilisée dans certaines pathologies psychiatriques telles que les troubles obsessionnels compulsifs ou la dépression. Elle commence à être envisagée, voire appliquée, comme traitement de certaines addictions. Nous faisons le point dans cette revue sur l’évolution des discussions sur l’intérêt de cette approche thérapeutique, et discutons en particulier les arguments expérimentaux orientant le choix vers les deux cibles cérébrales les plus pertinentes pour traiter les addictions par stimulation cérébrale profonde : le noyau accumbens (NAc) et le noyau sous-thalamique (NST)

Effects of GPi and STN inactivation on physiological, motor, cognitive and motivational processes in animal models of Parkinson's disease

International audienceLoss of the dopaminergic input to the striatum, characterizing Parkinson's disease, leads to the hyper-activity of two key nuclei of the basal ganglia (BG): the subthalamic nucleus (STN) and the internal segment of the globus pallidus (GPi). The anatomo-physiological organization of the BG and their output suggested that interfering with such hyper-activity could restore motor function and improve parkinsonism. Several animal models in rodents and primates, as well as clinical studies and neurosurgical treatments, have confirmed such hypothesis. This chapter will review the physiological and behavioural data obtained by inactivating the GPi or the STN by means of lesions, pharmacological approaches and deep brain stimulation. The consequences of these treatments will be examined at levels ranging from cellular to complex behavioural changes. Some of this experimental evidence suggested new and effective clinical treatments for PD, which are now routinely used worldwide. However, further studies are necessary to better understand the consequences of GPi and STN manipulation especially at the cognitive level in order to improve functional neurosurgical treatments for Parkinson's disease by minimizing risks of side-effects

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

Social modulation of drug use and drug addiction

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Beyond the Reward Pathway: Coding Reward Magnitude and Error in the Rat Subthalamic Nucleus

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