Topic: dorsolateral striatum

The direct and indirect pathways of the basal ganglia (BG) are classically thought to promote and suppress action, respectively. However, observed coactivation of neurons initiating the two pathways, striatal direct (dMSNs) and indirect (iMSNs) medium spiny neurons, has called this view into question. Here we study these circuits in mice performing an interval categorization task that requires a series of self-initiated and cued actions, and critically, a sustained period of dynamic action suppression. While movement produced similar activation of iMSNs and dMSNs in sensorimotor, dorsolateral

In recent years, advances in the fields of computational ethology and neuroscience have enabled detailed modeling of animal behavior and its neural underpinnings. However, these advances have yet to produce normative models of neuromotor control that generate the full diversity of animal behavior. Using recently developed methods in 3D pose estimation and deep reinforcement learning, we trained a latent variable model to control a virtual rodent body to imitate the natural behaviors of real rats in a physics simulator. Once trained, the model faithfully replicated diverse rat behaviors and gen

How does the activity of midbrain dopamine (DA) neurons influence behavior? A prominent, but incompletely tested, hypothesis is that the activity of ventral tegmental area (VTA) DA neurons generates downstream representations of state values in ventral striatum (NAc), while substantia nigra pars compacta DA activity generates action values in the dorsal striatum. To test this model, we performed Neuropixels recordings in a trial-and-error probabilistic learning task where mice continuously adapted their choices to obtain a reward of optogenetic stimulation of VTA DA neurons (paired with an aud

Neuromodulatory signals are powerful and prevalent influences on behavior. For example, dopaminergic inputs to the dorsolateral striatum are correlated with action selection and invigoration, and the loss of dopaminergic drive in Parkinson's disease manifests in deficits of movement timing and initiation. While the role of dopamine in the cortex-basal ganglia-thalamaus (C-BG-T) loop has been explored within the framework of reinforcement learning, computational models of how dopamine might influence fast-timescale movement generation have not been explored to the same extent. Here, we propose

Two striatal subregions, the Dorsolateral Striatum (DLS) and the Dorsomedial Striatum (DMS) are thought to implement habitual and flexible, goal-directed behavior respectively. The DMS has been shown to be involved in tasks such as gating of information into working memory and accumulating evidence before making a decision. How the DMS produces these behaviors is less understood than the DLS because, unlike habitual motor tasks used to study the DLS, tasks used to study the DMS require more management of internal mental states, an inherently unobservable process. In this work, we build a compu

Motor skills underlie much of what we do, from tying shoes to serving a volleyball. A hallmark of skills is a transition over learning, from variable behavior to precise and stereotyped movements. This change in motor variability must be flexibly, but tightly, regulated: while necessary to explore the motor space to find rewarded solutions, it impairs peak performance. However, how variability regulation is implemented in the mammalian brain remains unclear. The basal ganglia have been implicated, and a transition from dorsomedial striatum (DMS), mediating variable behavior, to dorsolateral st

Working memory is a transient representation of recently experienced that undergoes processes to make the information usable for goal-oriented behavior. Prior research emphasizes the prefrontal cortex's importance in working memory. This was demonstrated by inhibition (Bauer et al, 1976) and recording (Miller et al, 1996) experiments. However, most studies focus on the short-term aspect, neglecting the reference memory that got a crucial role in information utilization in working memory (Yoon et al,2008). Our investigation digs into the evolution of encoding learned information in reference me

Understanding the basal ganglia's role in initiating and executing action sequences is crucial for treating Parkinson's disease (PD). Recent experimental data challenge the classical model attributing pro- and anti-kinetic functions to direct and indirect pathways of the basal ganglia. To better understand movement-related neuronal activity in the basal ganglia, we performed large-scale electrophysiological recordings with Neuropixels probes in awake, behaving mice in the dorsomedial and dorsolateral striatum (DMS and DLS, respectively). We used the MitoPark mouse, a genetic model of PD, to in

Learning requires a multitude of steps until efficiency. The process of acquisition, consolidation and automatization depends on cortico-basal ganglia circuits. These circuits are topographically organized into parallel limbic, associative and sensorimotor loops coursing through the ventromedial (VMS), dorsomedial (DMS) and dorsolateral striatum (DLS), respectively; they dynamically interact and are recruited to different extents during initial, goal-directed and highly automatized learning stages, respectively. To date, a comprehensive expression profiling of the learning striatum is lacking.

Studies suggest that adaptive behaviors arise from multiple decision systems in the brain, and spatial complexity affects these processes. Three regions are hypothesized to make distinct contributions: hippocampus (HC) — encoding state-space and enabling flexible behaviors, dorsolateral striatum (DLS) — encoding action-chains and enabling automated behaviors, and prefrontal cortex (mPFC) — encoding task-space and strategy-setting. We simultaneously recorded across these regions, and in a separate cohort we chemogenetically inhibited mPFC on a rule-switch task, the left/right/alternation foragi

Parkinson's disease is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons, leading to a spectrum of motor and non-motor symptoms. While motor deficits serve as the primary criteria for diagnosis, emerging evidence suggests that non-motor symptoms may also significantly contribute to the disease's progression. In this study, our aim was to investigate the potential impact of IGF-1 on the progression of emotional-like behavioral deficits in a rat model of neurotoxicity induced by 6-OHDA infusion into the dorsolateral striatum. We evaluated behavioral chang

Aims: L-DOPA-induced dyskinesias (LID) cause disability in Parkinson’s disease patients undergoing L-DOPA treatment. It is known that maladaptive plastic changes in both pre-and post-synaptic components of striatal network contribute to LID. However, the possible role of perineuronal nets (PNN), a member of the tetrapartite synaptic unit, is still elusive. We aimed to investigate alterations in PNN structure mainly encapsulating parvalbumin positive interneurons (PV-IN) in a rat model of LID.Methods: 6-OHDA toxin-injected hemiparkinsonian, sham-operated, and naïve Wistar male rats received eit

The ability to learn associations between sensory stimuli, actions and outcomes is crucial for adaptive perceptual decision-making. A key brain area supporting this ability is the striatum, which receives extensive signals from several cortical areas. These cortico-striatal pathways are shaped by two neuromodulators, dopamine and acetylcholine, whose levels are among the highest in the brain. Yet, how dopamine and acetylcholine interact to facilitate adaptive perceptual decision-making is unclear. To address this question, we characterized dopamine and acetylcholine release in the dorsolateral