Spatially organized striatal neuromodulator release encodes trajectory errors.

Goal-directed navigation requires animals to continuously evaluate their current direction and speed of travel relative to landmarks to discern whether they are approaching or deviating from their goal. Striatal dopamine and acetylcholine are powerful modulators of goal-directed behavior, but it is unclear whether and how neuromodulator dynamics at landmarks incorporate relative motion for effective behavioral guidance. Using optical measurements in mice, we demonstrate that cue-evoked striatal dopamine release encodes bi-directional 'trajectory errors' reflecting relationships between ongoing speed and direction of locomotion and visual flow relative to optimal goal trajectories.

Spatially organized striatum-wide acetylcholine dynamics for the learning and extinction of Pavlovian cues and actions.

Striatal acetylcholine (ACh) has been linked to behavioral flexibility. A key component of flexibility is down-regulating responding as valued cues and actions become decoupled from positive outcomes. We used array fiber photometry in mice to investigate how ACh release across the striatum evolves during learning and extinction of Pavlovian associations.

Targeted micro-fiber arrays for measuring and manipulating localized multi-scale neural dynamics over large, deep brain volumes during behavior.

Neural population dynamics relevant to behavior vary over multiple spatial and temporal scales across three-dimensional volumes. Current optical approaches lack the spatial coverage and resolution necessary to measure and manipulate naturally occurring patterns of large-scale, distributed dynamics within and across deep brain regions such as the striatum. We designed a new micro-fiber array approach capable of chronically measuring and optogenetically manipulating local dynamics across over 100 targeted locations simultaneously in head-fixed and freely moving mice, enabling the investigation of cell-type- and neurotransmitter-specific signals over arbitrary 3D volumes at a spatial resolution and coverage previously inaccessible.

Targeted micro-fiber arrays for measuring and manipulating localized multi-scale neural dynamics over large, deep brain volumes during behavior.

Neural population dynamics relevant for behavior vary over multiple spatial and temporal scales across 3-dimensional volumes. Current optical approaches lack the spatial coverage and resolution necessary to measure and manipulate naturally occurring patterns of large-scale, distributed dynamics within and across deep brain regions such as the striatum. We designed a new micro-fiber array and imaging approach capable of chronically measuring and optogenetically manipulating local dynamics across over 100 targeted locations simultaneously in head-fixed and freely moving mice.

The antiparkinson drug ropinirole inhibits movement in a Parkinson's disease mouse model with residual dopamine neurons.

The dopamine (DA) D2-like receptor (D2R) agonist ropinirole is often used for early and middle stage Parkinson's disease (PD). However, this D2-like agonism-based strategy has a complicating problem: D2-like agonism may activate D2 autoreceptors on the residual DA neurons in the PD brain, potentially inhibiting these residual DA neurons and motor function. We have examined this possibility by using systemic and local drug administration in transcription factor Pitx3 null mutant (Pitx3Null) mice that mimic the DA denervation in early and middle stage PD and in DA neuron tyrosine hydroxylase (TH) gene knockout (KO) mice that mimic the severe DA loss in late stage PD.

Cyclic AMP-producing chemogenetic activation of indirect pathway striatal projection neurons and the downstream effects on the globus pallidus and subthalamic nucleus in freely moving mice.

The indirect pathway striatal medium spiny projection neurons (iMSNs) are critical to motor and cognitive brain functions. These neurons express a high level of cAMP-increasing adenosine A2a receptors. However, the potential effects of cAMP production on iMSN spiking activity have not been established, and recording identified iMSNs in freely moving animals is challenging.

Consequences of manganese intoxication on the circadian rest-activity rhythms in the rat.

Manganese (Mn) intoxication is associated with neurological dysfunctions collectively known as Parkinsonism or Manganism. Like in Parkinson's disease, Manganism is associated with motor disturbances, together with non-motor symptoms including cognitive and neuropsychiatric deficits. Although sleep dysfunctions are commonly reported among workers exposed to Mn, their underlying pathophysiology remains unknown.

Manganese neurotoxicity: behavioral disorders associated with dysfunctions in the basal ganglia and neurochemical transmission.

Manganese (Mn) is an essential element required for many physiological functions. While it is essential at physiological levels, excessive accumulation of Mn in the brain causes severe dysfunctions in the central nervous system known as manganism. Manganism is an extrapyramidal disorder characterized by motor disturbances associated with neuropsychiatric and cognitive disabilities similar to Parkinsonism.

Manganese-induced atypical parkinsonism is associated with altered Basal Ganglia activity and changes in tissue levels of monoamines in the rat.

Manganese neurotoxicity is associated with motor and cognitive disturbances known as Manganism. However, the mechanisms underlying these deficits remain unknown. Here we investigated the effects of manganese intoxication on motor and non-motor parkinsonian-like deficits such as locomotor activity, motor coordination, anxiety and "depressive-like" behaviors.