striatum

Prof Ian Oldenburg

The Oldenburg lab combines optics, multiphoton optogenetics, calcium imaging, and computation to understand the motor system. The overall goal of the Oldenburg Lab is to understand the causal relationship between neural activity and motor actions. We use advanced optical techniques such as multiphoton holographic optogenetics to control neural activity with an incredible degree of precision, writing complex patterns of activity to distributed groups of cells. Only by writing activity into the brain at the scale in which it naturally occurs (individual neurons firing distinct patterns of action potentials) can we test theories of what population activity means. We read out the effects of these precise manipulations locally with calcium imaging, in neighboring brain regions with electrophysiology, and at the 'whole animal level' through changes in behavior. We are looking for curious motivated, and talented people with a wide range of skill sets to join our group at all levels from Technician to Postdoc.

SWEBAGS conference 2024: The involvement of the striatum in autism spectrum disorder

Decomposing motivation into value and salience

Humans and other animals approach reward and avoid punishment and pay attention to cues predicting these events. Such motivated behavior thus appears to be guided by value, which directs behavior towards or away from positively or negatively valenced outcomes. Moreover, it is facilitated by (top-down) salience, which enhances attention to behaviorally relevant learned cues predicting the occurrence of valenced outcomes. Using human neuroimaging, we recently separated value (ventral striatum, posterior ventromedial prefrontal cortex) from salience (anterior ventromedial cortex, occipital cortex) in the domain of liquid reward and punishment. Moreover, we investigated potential drivers of learned salience: the probability and uncertainty with which valenced and non-valenced outcomes occur. We find that the brain dissociates valenced from non-valenced probability and uncertainty, which indicates that reinforcement matters for the brain, in addition to information provided by probability and uncertainty alone, regardless of valence. Finally, we assessed learning signals (unsigned prediction errors) that may underpin the acquisition of salience. Particularly the insula appears to be central for this function, encoding a subjective salience prediction error, similarly at the time of positively and negatively valenced outcomes. However, it appears to employ domain-specific time constants, leading to stronger salience signals in the aversive than the appetitive domain at the time of cues. These findings explain why previous research associated the insula with both valence-independent salience processing and with preferential encoding of the aversive domain. More generally, the distinction of value and salience appears to provide a useful framework for capturing the neural basis of motivated behavior.

Neuromodulation of striatal D1 cells shapes BOLD fluctuations in anatomically connected thalamic and cortical regions

Understanding how macroscale brain dynamics are shaped by microscale mechanisms is crucial in neuroscience. We investigate this relationship in animal models by directly manipulating cellular properties and measuring whole-brain responses using resting-state fMRI. Specifically, we explore the impact of chemogenetically neuromodulating D1 medium spiny neurons in the dorsomedial caudate putamen (CPdm) on BOLD dynamics within a striato-thalamo-cortical circuit in mice. Our findings indicate that CPdm neuromodulation alters BOLD dynamics in thalamic subregions projecting to the dorsomedial striatum, influencing both local and inter-regional connectivity in cortical areas. This study contributes to understanding structure–function relationships in shaping inter-regional communication between subcortical and cortical levels.

Dopamine and Acetylcholine waves in the striatum

Prefrontal top-down projections control context-dependent strategy selection

The rules governing behavior often vary with behavioral contexts. As a result, an action rewarded in one context may be discouraged in another. Animals and humans are capable of switching between behavioral strategies under different contexts and acting adaptively according to the variable rules, a flexibility that is thought to be mediated by the prefrontal cortex (PFC). However, how the PFC orchestrates the context-dependent switch of strategies remains unclear. Here we show that pathway-specific projection neurons in the medial PFC (mPFC) differentially contribute to context-instructed strategy selection. In mice trained in a decision-making task in which a previously established rule and a newly learned rule are associated with distinct contexts, the activity of mPFC neurons projecting to the dorsomedial striatum (mPFC-DMS) encodes the contexts and further represents decision strategies conforming to the old and new rules. Moreover, mPFC-DMS neuron activity is required for the context-instructed strategy selection. In contrast, the activity of mPFC neurons projecting to the ventral midline thalamus (mPFC-VMT) does not discriminate between the contexts, and represents the old rule even if mice have adopted the new one. Furthermore, these neurons act to prevent the strategy switch under the new rule. Our results suggest that mPFC-DMS neurons promote flexible strategy selection guided by contexts, whereas mPFC-VMT neurons favor fixed strategy selection by preserving old rules.

Mapping learning and decision-making algorithms onto brain circuitry

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 decision-making mechanisms in the striatum.

PPN inputs to striatum

Mechanisms and Roles of Fast Dopamine Signaling

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.

Cell assembly activation coordinated by rhythmic oscillation in the prefrontal-ventral striatum-hippocampal network

Synaptic alterations in the striatum drive ASD-related behaviors in mice

Experience-dependent remapping of temporal encoding by striatal ensembles

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 without reward. We report three main results. First, we found that the proportion of MSNs exhibiting time-dependent modulations of firing rate increased after 10 days of task overtraining. Second, temporal decoding by MSN ensembles increased with experience and was largely driven by time-related ramping activity. Finally, we found that time-related ramping activity generalized across both correct and error trials. These results enhance our understanding of striatal temporal processing by demonstrating that time-dependent activity within MSN ensembles evolves with experience and is dissociable from motor- and reward-related processes.

What about antibiotics for the treatment of the dyskinesia induced by L-DOPA?

L-DOPA-induced dyskinesia is a debilitating adverse effect of treating Parkinson’s disease with this drug. New therapeutic approaches that prevent or attenuate this side effect is clearly needed. Wistar adult male rats submitted to 6-hydroxydopamine-induced unilateral medial forebrain bundle lesions were treated with L-DOPA (oral or subcutaneous, 20 mg kg-1) once a day for 14 days. After this period, we tested if doxycycline (40 mg kg-1, intraperitoneal, a subantimicrobial dose) and COL-3 (50 and 100 nmol, intracerebroventricular) could reverse LID. In an additional experiment, doxycycline was also administered repeatedly with L-DOPA to verify if it would prevent LID development. A single injection of doxycycline or COL-3 together with L-DOPA attenuated the dyskinesia. Co-treatment with doxycycline from the first day of L-DOPA suppressed the onset of dyskinesia. The improved motor responses to L-DOPA remained intact in the presence of doxycycline or COL-3, indicating the preservation of L-DOPA-produced benefits. Doxycycline treatment was associated with decreased immunoreactivity of FosB, cyclooxygenase-2, the astroglial protein GFAP and the microglial protein OX-42 which are elevated in the basal ganglia of rats exhibiting dyskinesia. Doxycycline also decreased metalloproteinase-2/-9 activity, metalloproteinase-3 expression and reactive oxygen species production. Metalloproteinase-2/-9 activity and production of reactive oxygen species in the basal ganglia of dyskinetic rats showed a significant correlation with the intensity of dyskinesia. The present study demonstrates the anti-dyskinetic potential of doxycycline and its analog compound COL-3 in hemiparkinsonian rats. Given the long-established and safe clinical use of doxycycline, this study suggests that these drugs might be tested to reduce or to prevent L-DOPA-induced dyskinesia in Parkinson’s patients.

Neurotoxicity is a major health problem in Africa: focus on Parkinson's / Parkinsonism

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 earlier and this is particularly the case with anxiety, depression, anhedonia, and sleep disturbances. In 90 to 95% of cases, the causes of the appearance of the disease remain unknown, but polluting toxic molecules are incriminated more and more. In Africa, neurodegenerative diseases of the Parkinson's type are increasingly present and a parallel seems to exist between the increase in cases and the presence of toxic and polluting products such as metals. My Web conference will focus on this aspect, i.e. present experimental arguments which reinforce the hypothesis of the incrimination of these pollutants in the incidence of Parkinson's disease and / or Parkinsonism. Among the lines of research that we have developed in my laboratory in Rabat, Morocco, I have chosen this one knowing that many of our PhD students and IBRO Alumni are working or trying to develop scientific research on neurotoxicity in correlation with pathologies of the brain.

The Dopamine Synapse and Learning

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.

Male songbirds turn off their self-evaluation systems when they sing to females

Attending to mistakes while practicing alone provides opportunities for learning but self-evaluation during audience-directed performance could distract from ongoing execution. It remains unknown how animals switch between practice and performance modes, and how evaluation systems process errors across distinct performance contexts. We recorded from striatal-projecting dopamine (DA) neurons as male songbirds transitioned from singing alone to singing female-directed courtship song. In the presence of the female, singing-related performance error signals were reduced or gated off and DA neurons were instead phasically activated by female vocalizations. Mesostriatal DA neurons can thus dynamically change their tuning with changes in social context.

Delineating Reward/Avoidance Decision Process in the Impulsive-compulsive Spectrum Disorders through a Probabilistic Reversal Learning Task

Impulsivity and compulsivity are behavioural traits that underlie many aspects of decision-making and form the characteristic symptoms of Obsessive Compulsive Disorder (OCD) and Gambling Disorder (GD). The neural underpinnings of aspects of reward and avoidance learning under the expression of these traits and symptoms are only partially understood. " "The present study combined behavioural modelling and neuroimaging technique to examine brain activity associated with critical phases of reward and loss processing in OCD and GD. " "Forty-two healthy controls (HC), forty OCD and twenty-three GD participants were recruited in our study to complete a two-session reinforcement learning (RL) task featuring a “probability switch (PS)” with imaging scanning. Finally, 39 HC (20F/19M, 34 yrs +/- 9.47), 28 OCD (14F/14M, 32.11 yrs ±9.53) and 16 GD (4F/12M, 35.53yrs ± 12.20) were included with both behavioural and imaging data available. The functional imaging was conducted by using 3.0-T SIEMENS MAGNETOM Skyra syngo MR D13C at Monash Biomedical Imaging. Each volume compromised 34 coronal slices of 3 mm thickness with 2000 ms TR and 30 ms TE. A total of 479 volumes were acquired for each participant in each session in an interleaved-ascending manner. " " The standard Q-learning model was fitted to the observed behavioural data and the Bayesian model was used for the parameter estimation. Imaging analysis was conducted using SPM12 (Welcome Department of Imaging Neuroscience, London, United Kingdom) in the Matlab (R2015b) environment. The pre-processing commenced with the slice timing, realignment, normalization to MNI space according to T1-weighted image and smoothing with a 8 mm Gaussian kernel. " " The frontostriatal brain circuit including the putamen and medial orbitofrontal (mOFC) were significantly more active in response to receiving reward and avoiding punishment compared to receiving an aversive outcome and missing reward at 0.001 with FWE correction at cluster level; While the right insula showed greater activation in response to missing rewards and receiving punishment. Compared to healthy participants, GD patients showed significantly lower activation in the left superior frontal and posterior cingulum at 0.001 for the gain omission. " " The reward prediction error (PE) signal was found positively correlated with the activation at several clusters expanding across cortical and subcortical region including the striatum, cingulate, bilateral insula, thalamus and superior frontal at 0.001 with FWE correction at cluster level. The GD patients showed a trend of decreased reward PE response in the right precentral extending to left posterior cingulate compared to controls at 0.05 with FWE correction. " " The aversive PE signal was negatively correlated with brain activity in regions including bilateral thalamus, hippocampus, insula and striatum at 0.001 with FWE correction. Compared with the control group, GD group showed an increased aversive PE activation in the cluster encompassing right thalamus and right hippocampus, and also the right middle frontal extending to the right anterior cingulum at 0.005 with FWE correction. " " Through the reversal learning task, the study provided a further support of the dissociable brain circuits for distinct phases of reward and avoidance learning. Also, the OCD and GD is characterised by aberrant patterns of reward and avoidance processing.

Broadly-projecting mesolimbic dopamine neurons implement a distributional critic across the striatum

COSYNE 2025

Cell-type specific transcriptional changes in the striatum of a 6-hydroxydopamine mouse model

Dopamine dynamics in the mouse dorsal striatum during locomotion and postural shifts

Electroconvulsive therapy promotes reinnervation of the dopamine-depleted striatum in the 6-OHDA model of Parkinson’s disease

FENS Forum 2024

Role of parkinsonism-associated protein Fbxo7 in synaptic integrity of the striatum & olfactory bulb

Differential encoding of innate and learned behaviors in the sensorimotor striatum

COSYNE 2022

How does the dorsal striatum contribute to active choice rejection?

COSYNE 2022

What role for the striatum in motor control? Insights from unilateral perturbation during foraging

FENS Forum 2024

Functional consequences of highly shared feedforward inhibition in the striatum

COSYNE 2023

Dopamine signaling for perceptual learning in the sensory striatum

COSYNE 2025

Hunger modulates exploration through dopamine signaling at the tail of striatum

COSYNE 2025

Layered, hierarchical behavioral control underlies dopamine signals across the striatum during decision-making

COSYNE 2025

A Multi-region, Multi-task RNN Model of How Dorsomedial Striatum Implements Flexible Behavior

COSYNE 2025

Sensory Prediction Error signals in Tail of the Striatum Dopamine

COSYNE 2025

Beta oscillations in the monkey striatum encodes reward prediction error

Cell Type Specific Auditory Responses in the Auditory Striatum

Compulsive Sexual Behavior Disorder Impact On Striatum and Amygdala Functional Responses During Appetitive Conditioning and Extinction

Deletion of the dopamine transporter depotentiates the glutamatergic neurotransmission in the rat striatum

Differential dopamine signalling in ventral and dorsal striatum in vivo

Distinct involvement of direct and indirect pathways from the dorsolateral and dorsomedial striatum in the pathophysiology of Huntington’s disease

Distinct roles of dopamine and direct- and indirect-pathway neurons in the tail of the striatum in threat management in a semi-naturalistic foraging task

Intermittent hypoxia promotes post-stroke recovery in rodent striatum through neurogenesis

Investigating the implication of rat dorsal striatum in action selection using a conflict task

Involvement of serotoninergic projections to the dorsal striatum in behavioural switching under uncertainty

Isolation of dopaminergic inputs to the striatum reveals dopamine hub synapses with their proteome

JAK2-STAT3-dependent molecular signature in reactive astrocytes of the mouse striatum

Lipopolysaccharide-induced neuroinflammation in the posterior dorsomedial striatum facilitates goal-directed action

Mapping the projection from barrel cortex to the direct and indirect pathways of dorsal striatum using a functional approach

A molecular map of the learning striatum

Neural oscillations in striatum-hippocampus-amygdala network during a double Pavlovian conditioning in rats

Opposing changes in the activity of direct and indirect pathways within the striatum of freely moving DYT-TOR1A dystonic mice

Phosphodiesterase 2A : functional role in the striatum and potentially new therapeutic target in Parkinson’s disease

Phosphodiesterases as integrators of the dopamine signal in the striatum

Preventive exercise counteracts glutamatergic transmission defects in the striatum of mice with experimental autoimmune encephalomyelitis

Pyramidal tract neurons amplify excitation to the striatum through cholinergic interneurons

Reinforcement learning of abstract rules involves the prefrontal cortex and the striatum

Replay of motor sequences in dorsolateral striatum during offline consolidation are revealed using a unsupervised point process model

Representation of action value and uncertainty across dorsal striatum

Restoration of dopamine D2 receptors in the sensorimotor striatum of D2R knockdown mice selectively ameliorates deficits in motor skill learning

Role of group I metabotropic receptors in the synaptic alterations in the dorsal striatum of the R451C-Nlgn3 mouse model of autism