Biederer
Understanding and manipulating cellular and circuit-level vulnerability to neurodegeneration in Parkinson’s disease
Active
Circuitry and Brain-Body Interactions
The Circuitry and Brain-Body Interactions theme within the ASAP Collaborative Research Network (CRN) focuses on understanding how Parkinson’s disease (PD) affects isolated neurons and entire neural circuits and connections between the brain and the body.Researchers in this area study how disruptions in motor and non-motor pathways contribute to PD symptoms, and how peripheral systems – like the gut, immune system, and autonomic nervous system – interact with the brain to influence disease onset and progression. This theme aims to uncover how early changes across interconnected systems could serve as warning signs, contribute to disease spread, or offer new targets for intervention.
Highlights
Excitatory synaptic structural abnormalities produced by templated aggregation of α-syn in the basolateral amygdala
PD and DLB involve α-syn inclusions in the amygdala affecting cognition and emotions. Cortico-amygdala synapses with α-syn aggregates show increased volume of synapses, potentially contributing to behavioral impairments.
State-dependent modulation of spiny projection neurons controls levodopa-induced dyskinesia in a mouse model of Parkinson’s disease
LID is poorly understood, our research on dyskinetic mice show SPNs' properties oscillate during LID and are influenced by dopamine and acetylcholine signaling. Targeting M1 receptors in iSPNs reduced LID severity and improved levodopa effects.
Striatal dopamine signals internal states related to behavioral performance over prolonged timescales in monkeys
Dopamine plays dual roles in behavior: fast reward prediction errors and slow motivational states. Dopamine release in monkeys' brain regions tracks performance changes, suggesting a single signal for both functions.
Thalamus orchestrates local acetylcholine-dependent dopamine release in the learning striatum
Thalamic input can trigger dopamine release in the striatum during motor learning, likely reflecting action vigor rather than motor error. Changes in this mode of dopamine release may contribute to motor and non-motor symptoms of PD.
Our Teams
Calakos
Circuit Mechanisms for Dopamine Neuron Vulnerability and Resilience in PD
Cragg
Mapping the modulatory landscape governing striatal dopamine signaling and its dysregulation in Parkinson’s disease
Dombeck
Redefining PD pathophysiology mechanisms in the context of heterogeneous substantia nigra neuron subtypes
Edwards
The Dual Role of Neural Activity in Parkinson's Disease
Gradinaru
Gut-to-brain circuit contributions to Parkinson-like phenotypes in nontransgenic rodent and primate animal models
Kaplitt
α-Synuclein Effects on Gut Brain Circuits and Pre-Motor Symptoms in Parkinson’s Disease
Liddle
Role of enteroendocrine cells in the origin of Parkinson’s pathology
Mobley
Reconstructing the Lost Nigrostriatal Circuitry in Parkinson's Disease
Schlossmacher
Olfactory Circuits: Alpha-Synuclein-Rich Neurons Respond to Environmental Triggers at the Origin of Parkinson Disease
Strick
Basal Ganglia Networks in Parkinson’s Disease
Surmeier
Distributed circuit dysfunction underlying motor and sleep deficits in a progressive mouse model of Parkinson’s disease
Vila
Activity and connectivity drive neuronal vulnerability and disease progression in Parkinson’s disease
Wichmann
Cortical pathophysiology of Parkinsonism
