Striatum

…distinct neural populations in the striatum alongside motor output, muscle activity and behavioral video. The project asks how shared and population-specific neural activity encodes movement, using latent-variable models, regression, classification and cross-validation. Work includes reproducible Python analysis and communicating results through figures and methods that may contribute to a poster or publication. No previous neuroscience b

Animal behavior is controlled through the coordinated action of multiple learning systems in the brain. One of these systems, the basal ganglia, instantiates a reinforcement learning (RL) algorithm in which dopamine (DA) neurons transmit reward prediction error (RPE) signals---the difference between actual and expected rewards---to enable value learning via cortico-striatal plasticity. Recent studies have highlighted two novel aspects: first, that RPE signals from midbrain DA neurons can encode entire reward distributions through a distributional RL algorithm that mirrors cutting-edge machine

…modulated by dopamine release in the striatum, a prediction-error teaching signal that allows animals to learn from both rewards and threats depending on the striatal subregion in which dopamine is released. Exploration and dopamine signaling are modulated by internal state, including caloric depletion or “hunger”, such that when animals are hungry they explore their environment more, presumably in an attempt to find food. While this adaptation has been known for decades, the n

…movement begins, frontal cortex and striatum exhibit ramping spiking activity, with variable ramp slopes anticipating movement onsets. This activity in the cortico-basal ganglia loop may function as an adjustable ‘timer’, triggering actions at the desired timing. However, because the frontal cortex and striatum share similar ramping dynamics and are both necessary for timing behaviors, distinguishing their individual roles in this timer function remains challenging. To address this fundamental gap, we introduced two-re

…errors (RPEs), to all regions of the striatum [1]. However, these signals converge with regionally segregated inputs from all levels of the cortical hierarchy [2] that vary in degree of abstraction and temporal extendedness [3]. Recent work highlights how regionally diverse DA RPEs might update parallel estimates of future reward as informed by region-specific inputs[4, 5], yet the behavioral implications of such parallel processing are poorly understood. We used photometry to measure DA release across the striatum in mice

…between amygdala, frontal cortex, and striatum is critical for this type of learning. Here, we conducted neurophysiology recordings and applied computational approaches to understand how activity in this circuit varies when choice and reward are separated in time, intentionally decreasing animals’ ability to associate the two together. We trained 3 rhesus macaques to perform a probabilistic reward-learning task. In each session, animals learn the probabi

…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

…recording activity across cortex and striatum, while inhibiting the direct or indirect basal ganglia pathway as mice perform an evidence-accumulation task in which each manipulation produces opposing decision biases. Inconsistent wit

Early postnatal development is a critical period for the establishment of functional brain networks. While extensive research has focused on local circuit maturation, the emergence and evolution of long-range communication between brain regions has received less attention. Here we investigate the developmental trajectory of inter-regional communication in the mouse brain over the first two postnatal weeks of life, a period characterised by rapid synaptogenesis followed by activity-dependent pruning and circuit refinement. We leverage electrophysiological datasets of population activity simulta

…The prefrontal cortex and striatum are both essential to cognitive flexibility but competing theories debate which structure among these two leads the role in detecting and representing new circumstances for a change, giving largely opposing predictions on neural activities in the prefrontal cortex and striatum during flexible behavior. We trained head-restrained mice to perform an action-outcome based dynamic foraging task and simultaneously recorded single-neuron activities in the medial prefrontal cortex (mPFC)

Our ability to develop, learn, and adapt depends on the brain’s capacity to change over time. To analyze plasticity processes over time in individual animals, we introduced a novel technique that enables immediate-early gene (IEG) activity to be mapped noninvasively using magnetic resonance imaging (MRI). Using this method, called IEG BLUsH, we interrogated the spatiotemporal relationships between neural activity and plasticity gene induction in an opioid administration paradigm. IEG activity and functional MRI (fMRI) signals were recorded following fentanyl treatments lasting several days (Fi

…some brain areas such as hippocampus, striatum and prefrontal cortex. Nevertheless, the mechanism underlying depression remain elusive, and so, an effective treatment. To tackle this issue, cannabidiol (CBD) treatment has emerged as a

…changes in prefrontal cortex and striatum, and 3- possible sex-based differences. METHODS: Recombinant adeno-associated viral vectors (AAV2/5) encoding wild-type human a-Syn (h-a-Syn) were infused in r

The neuronal population of the striatum is primarily composed of medium spiny projecting neurons (MSNs), with only a small percentage (around 5% in mice) being locally projecting neurons or interneurons. Despite their low numbers, interneurons play a crucial role in regulating the flow of information within the striatum and to other brain nuclei, thereby having significant implications for motor control and cognition.We recently identified one of the most abundant populations of GABAergic interneurons in the striatum that express Pthlh and varying levels of Pvalb, which correlates with intrins

…disease that damages primarily the striatum and leads to motor, cognitive and psychiatric symptoms. The HD striatum undergoes early specific epigenetic gene reprogramming, leading to progressive impairment of striatal neuron identity and function. Notably, genes that define striatal neuron identity are progressively down-regulated due to decreased histone acetylation (e.g. H3K27 acetylation -H3K27ac-). Additionally, developmental genes show an increase in H3K27ac, leading to their derepression. Histone acetylation is strongly connected t

…form vast axonal arbours in the striatum, presenting opportunities for local axonal regulation of DA signalling by diverse interacting mechanisms. Striatal DA transporters (DATs) and γ-aminobutyric acid receptors (GABA-Rs) are both thought to limit DA axon activation and thereby attenuate DA release probability whilst also supporting the frequency-dependence of DA release. We tested whether these convergent mec

Our previous studies have shown that the water influx via astrocytic AQP4 induces the release of ATP and subsequent increase of extracellular adenosine. Since antagonistic interactions between adenosine and dopamine have been shown by biochemical and pharmacological studies, the present study investigated the possibility that the AQP4-dependent adenosine increase interacts with dopamine neurotransmission, focusing on the effects of cocaine. The stimulus effect of acute cocaine treatment was abolished in AQP4 ko mice, while mice treated with caffeine for one week showed the increase of the stim

Mucopolysaccharidosis type IIIA (MPS-IIIA) is a rare genetic metabolism disorder, belonging to the class of Lysosomal Storage Disorders (LSD). MPS-IIIA is caused by a mutation in the gene SGSH, leading to lysosomal enzyme sulfamidase deficiency and impaired degradation of heparan sulfate. Although the disease manifests during early childhood as an autistic spectrum disorder (ASD), the causes of ASD in MPS-IIIA are only poorly explored. Using a genetic mouse model of MPS-IIIA, we have recently discovered that these autistic-like behavioural symptoms (ALBs), which are known to be subtly regula

…specific cell populations of the striatum - the input nucleus of the basal ganglia - during movements. We recorded the activity of direct and indirect pathway medium spiny neurons (dMSNs and iMSNs) in the striatum as mice performed a skilled motor task, by in vivo two-photon calcium imaging through GRIN lens. Further

The striatum intricately regulates motor and cognitive functions through the dynamic interplay of dopamine (DA), acetylcholine (ACh), and intrinsic neuronal firing, bearing profound implications for disorders like Parkinson's. However, the interaction between striatal DA and ACh, and their collective impact on striatal neuron activity in health and disease, are not fully understood. This study aims to elucidate the complex interplay between ACh, DA, and neuronal activity in the striatum during sensory and motor events. Utilizing a specialized Delayed-Go reaching task for head-fixed mice, we re

…delivery of GDF5 and GDNF to the striatum (putamen), a more clinica

Parkinson's disease (PD) is a progressive neurodegenerative disorder, characterized by resting tremor, rigidity, and bradykinesia. Additionally, a wide spectrum of early non-motor symptoms has been described, among which cognitive impairment is one of the most relevant.Several studies show that interventions focused on cognitive stimulation can play an important role in preventing or delaying the onset of dementia in patients with neurodegenerative diseases. In this perspective, we aimed at investigating the synaptic mechanisms mediating the effects of cognitive enrichment in two mouse models

Anti-NMDA receptor (NMDAR) encephalitis is associated with the presence of autoantibodies against subunit 1 of the NMDA receptor (NR1) resulting in a variety of psychiatric symptoms as well as cognitive and motor impairments. These autoantibodies can arise in adulthood but also during pregnancy where they have been shown to affect the developing foetal brain and are implicated in neurodevelopmental disorders including autism and learning disabilities. Binding of these autoantibodies causes internalization of surface NMDAR leading to their reduced expression and disrupted signalling. To what ex

…of dopamine D2 receptors (D2R) in the striatum of schizophrenia patient