Topic: dorsal striatum

Imagine that it’s tea time and you’d like to eat a distant cookie. The speed at which you will walk toward this cookie will be modulated by your sensitivities to the energetic cost of movement (e.g., lazy vs. energetic), to the cost of time (e.g., patient vs. impatient), and to the reward (e.g., hungry vs. sated). How these sensitivities modulate behavior and their neural implementation remain poorly understood. Here, we tackled this question by combining experimental and theoretical approaches. We developed an automated foraging task in which rats have to run back and forth on a treadmill to

Recent advances in recording techniques and behavioral monitoring are revolutionizing systems neuroscience, enabling the study of behavior in naturalistic settings. Using fiber photometry data from dopamine axons (DA) in the striatum, we set out to characterize the homogeneity and heterogeneity across striatal areas during naturalistic behavior. These recordings were performed while a mouse explored multiple items placed inside a box, with which they could interact freely. Specifically, our goal was to test the hypothesis that DA axons in the ventral striatum (VS) solely encode value informati

How quickly humans and other animals take decisions and move often covary with the utility of their goals, suggesting the existence of a shared mechanism controlling the speeds of action selection and execution. To test this hypothesis, we developed a self-paced foraging task in which rats run back-and-forth across a motorized treadmill to collect drops of water, and separately manipulated reward and effort. We used simple models to 1) quantify changes in running speed and in the pause between runs (run and inter-run durations) and 2) explore algorithmic and neural principles controlling these

The advent of dLight, a class of genetically encoded dopamine sensor, has significantlyadvanced our ability to monitor real-time dopamine dynamics in living animals. The success ofdLight1.3b with its superior dynamic ranges has prompted the development of subsequentiterations of this sensor to broaden the applicability of in vivo dopamine monitoring, particularlyin brain regions characterized by sparse dopaminergic signaling. In this study, we present asystematic and extensive in vivo characterization of novel dLight variants (dLight3.6 &dLight3.8) in comparison to the dLight1.3b parents s

Learning by experience that certain cues in the environment predict danger is crucial for survival. How dopamine (DA) circuits drive this form of associative learning is not fully understood. Here, we demonstrate that DA neurons projecting to a unique subregion of the dorsal striatum, the posterior tail of the striatum (TS), encode an aversive prediction error (PE) signal during associative fear learning. These DA neurons are necessary specifically during acquisition of fear learning, but not once the fear memory is formed, and are not required for forming cue-reward associations. Notably, tem

Electroconvulsive therapy (ECT) is a well-established treatment for psychiatric disorders. Recent reports show that ECT improves motor deficits in Parkinson's disease (PD), while the mechanism of action remains unclear. To investigate the effects of ECT in PD, we produced partial dopaminergic depletion by unilateral striatal injection of 6-OHDA. After three weeks, behavioral testing was performed using the open field and corridor test. Animals with a lateralized phenotype were randomized into ECT or sham treatment. After a two-week treatment interval with daily ECT, behavioral testing was repe

Anorexia Nervosa (AN) is a multifactorial mental disorder characterized by voluntary food restriction and excessive physical activity leading to dramatic weight loss. The Brain-Derived Neurotropic Factor (BNDF) gene has been associated with AN. In rodents, both central and peripheral BDNF have been found to induce weight loss and anorexic effects. Thus, besides its function in neuronal development and mood, BDNF also acts as a metabolic regulator, making it a candidate biomarker for AN diagnosis. We used C57BL/6J female mice under 2-week 50% food restriction with access to running wheels to mi

The basal ganglia (BG) are involved in various functions such as movement regulation and decision-making. As the main input structure, the dorsal striatum constitutes the primary integration hub for sensory and motor, cortical and subcortical information. Exploring BG function requires analyzing how striatal neurons select and integrate sensory information. Studies of corticostriatal connectivity have long been centered on striatal projections neurons (SPNs), representing approximately 95% of the striatal cells and our group has recently showed the discrete nature of their sensory innervations

Parkinson's disease (PD) is a complex neurodegenerative movement disorder. The central pathological feature of PD is the progressive loss of dopaminergic neurons in the substantia nigra pars compacta, that project to the dorsal striatum. The resulting dopamine deficiency in this area dysregulates the striatal neural net, causing the motor deficits of PD patients. However, the process leading dopamine's depletion into neural deficits and how it can reflect on cortical activity is still largely unknown. This project's goal is to investigate the electrophysiological and functional changes affecti

Parkinson’s disease (PD) is characterized by the selective loss of dopaminergic neurons in the Substantia Nigra and Lewy body formation, resulting in a progressive neurodegenerative disorder with movement defects. The impairment of dopaminergic innervation in PD hinders the two main projection systems from the dorsal striatum (Putamen, Pu, and Caudate Nucleus, CN) from effectively responding to cortical and thalamic signals.A potential role of Oligodendrocytes (OLs) in PD was pointed out by recent works describing GWAS PD variants associated with OLs (Bryois et al, Nat Genet, 2020), PD genes e

Animals of the same species exhibit similar behaviours that are advantageously adapted to their body and environment. These behaviours are shaped at the species level by selection pressures over evolutionary timescales. Yet, it remains unclear how these common behavioural adaptations emerge from the idiosyncratic neural circuitry of each individual. The overall organisation of neural circuits is preserved across individuals because of their common evolutionarily specified developmental programme. Such organisation at the circuit level may constrain neural activity, leading to low-dimensional l

The basal ganglia are notorious for their influence on action control and modulation of movements. Proper organization of neuronal activity within the two efferent pathways of the dorsal striatum, a major input of basal ganglia, is critical for appropriate behavioral control. The classical model of basal ganglia suggests that striatal indirect and direct pathways exert opposite action on the thalamo-cortical activation triggering motor control. Recent studies challenged this view by describing conjoint neuronal activities during action initiation or decision-making. Therefore, additional inves

Adaptive behavior in a dynamically changing environment requires learning the value of actions, and updating these values in response to changes in the environment. Several studies have investigated the role of the striatum, and its key neuromodulators, dopamine (DA) and acetylcholine (Ach), in this process. However, these studies usually investigated these neuromodulatory signals in animals which had undergone extensive pre-training, and were thus experts at flexibly adapting to new action values. In addition, most of these studies did not explore the dynamics of these signals simultaneously,

The substantia nigra pars reticulata (SNr) is a primary output for basal ganglia signalling. It plays an important role in motor control, integrating inputs from upstream structures in the basal ganglia, before sending organised projections to a wide range of targets in the midbrain, brainstem and thalamus. Here we present a detailed in silico model of the mouse SNr, including its afferent inputs. The electrophysiological and morphological properties of SNr neurons are characterised in acute brain slices via whole cell patch-clamp and morphological reconstruction. Using reconstructed morpholog

The basal ganglia (BG) is a group of sub-cortical nuclei involved in motor control, learning and attention. The primary input nucleus of the BG is the striatum which receives cortical, thalamic and midbrain afferences on its two striatal projecting neurons’ (SPN) populations (the direct (d) and indirect (i) pathways) in a manner that remains elusive. Research on SPNs has mainly focused on characterizing its involvement in motor control rather than single neuron activity evolution during the process of action learning. This project aimed to dissect the relative contributions of both d- and i-SP

Sensorimotor regions of the neocortex send dense projections to the dorsal striatum making this region of basal ganglia an important structure of sensory integration. Anatomically, this innervation is diffuse, with axons from various cortical areas overlapping in the same striatal region. This suggests significant integration of information by striatal projection neurons (SPNs), contributing to the striatum’s role in decision making. However, the specific role of neurons forming direct and indirect pathways (d/iSPNs), as well as the level of convergence within one sensory modality onto single

The glycine receptor alpha 2 (GlyRα2) is the only functionally expressed glycine receptor in adult striatal projection neurons (SPNs) and an important modulator of signal integration within the dorsal striatum. SPNs are a convergence point for glutamatergic and dopaminergic input, which is key to reward-motivated behavior. Thus, targeting GlyRα2 offers great potential to modulate striatum-orchestrated behavior. However, the impact of GlyRα2's subcellular localization on SPN activity regulation remains unclear.Neurons are morphologically complex cells, containing many subcellular compartments (

In their daily life, humans and other animals continuously face the need to quickly remember what to do in familiar contexts and how to do it. Generally, the basal ganglia, and more specifically the dorsal striatum (dStr), are believed to be implicated in high-level functions (storage of procedural memories and/or action selection/suppression) and therefore drive the execution of learned actions. However, other studies have shown that the dStr might also be implicated in the moment-to-moment kinematics specification of learned movements, or the vigor of reward-oriented actions, which reflect m