Topic: striatum

A one-year machine-learning research internship with the Allen Institute Neural Dynamics accelerator. The intern will analyze recordings from two genetically 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

In the first half of my talk, I will discuss our recent work on the midbrain dopamine system. The hypothesis that midbrain dopamine neurons broadcast an error signal for the prediction of reward is among the great successes of computational neuroscience. However, our recent results contradict a core aspect of this theory: that the neurons uniformly convey a scalar, global signal. I will review this work, as well as our new efforts to update models of the neural basis of reinforcement learning with our data. In the second half of my talk, I will discuss our recent findings of state-dependent de

Dopamine is a neuromodulator that codes information on various time scales. I will discuss recent progress on the identification of fast release mechanisms for dopamine in the mouse striatum. I will present data on triggering mechanisms of dopamine release and evaluate its roles in striatal regulation. In the long-term, our work will allow for a better understanding of the mechanisms and time scales of dopamine coding in health and disease.

It is well established that midbrain dopaminergic neurons support reinforcement learning (RL) in the basal ganglia by transmitting a reward prediction error (RPE) to the striatum. In particular, different computational models and experiments have shown that a striatum-wide RPE signal can support RL over a small discrete set of actions (e.g. no/no-go, choose left/right). However, there is mounting evidence that the basal ganglia functions not as a selector between predefined actions, but rather as a dynamical system with graded, continuous outputs. To reconcile this view with RL, there is a nee

Medium-spiny neurons (MSNs) in the striatum are required for interval timing, or the estimation of the time over several seconds via a motor response. We and others have shown that striatal MSNs can encode the duration of temporal intervals via time-dependent ramping activity, progressive monotonic changes in firing rate preceding behaviorally salient points in time. Here, we investigated how timing-related activity within striatal ensembles changes with experience. We leveraged a rodent-optimized interval timing task in which mice ‘switch’ response ports after an amount of time has passed

Parkinson's disease (PD) is the second most present neurodegenerative disease in the world after Alzheimer's. It is due to the progressive and irreversible loss of dopaminergic neurons of the substantia nigra Pars Compacta. Alpha synuclein deposits and the appearance of Lewi bodies are systematically associated with it. PD is characterized by four cardinal motor symptoms: bradykinesia / akinesia, rigidity, postural instability and tremors at rest. These symptoms appear when 80% of the dopaminergic endings disappear in the striatum. According to Braak's theory, non-motor symptoms appear much ea

The actions of dopamine within the striatum are central to the selection of cortical and perhaps thalamic inputs that mediate learning throughout life, including during operant conditioning, reward and avoidance learning and the establishment of motor patterns. Dysfunction of these synaptic circuits during maturation or aging underlies many neurological, psychiatric and neurodevelopment disorders. We will discuss the biological sequences by which these synapses are altered as an animal interacts with the environment.

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

Hydrocephalus is associated with raised intracranial pressure (ICP) and has been implicated as the cause of endocrine dysfunction. Raised ICP results in distension of the third ventricle leading to compression of diencephalic structures and the hypothalamic-hypophyseal pathway. In this study, we aimed to assess the serum level of growth hormone and the histological changes in anterior pituitary gland of experimentally induced juvenile hydrocephalic rats. Hydrocephalus was induced in 3-week-old albino Wistar rats through intracisternal injection of sterile kaolin while age matched control rats

Arginase 2 (Arg2), an arginine-metabolizing, mitochondrial enzyme, has been recently found to be enriched in the striatum, and progressive loss of Arg2 has been proposed as a potential factor contributing to the pathogenesis of Huntington’s disease (HD), a disorder primarily involving this region of the brain. Although direct metabolic role of Arg2 is well established, the importance of this enzyme for striatal function and dysfunction is not known. The purpose of this work was to identify cellular pathways potentially controlled by Arg2 in the striatum. In our experiments, we have used wild-t

The striatum is densely innervated by midbrain dopamine (DA) neurons but also receives a further sparse monoaminergic innervation by raphe serotonin (5-HT) neurons. Striatal 5-HT has been suggested to have some opposing functions to DA but also to regulate DA release which might support (or counteract) this functional antagonism. We explored the reciprocal modulation of electrically evoked striatal DA and 5-HT release and the underlying cell circuits by using fast-scan cyclic voltammetry to detect DA, a new G-protein-coupled receptor sensor for 5-HT (GRAB5-HT3.0) and whole-cell recordings in a