Preserving Motor Engrams in Parkinson's Disease: Neural Circuit and Transcriptomic Studies and Strategies for Resilient Motor Control (renewed)

Preserving motor engrams in Parkinson's disease: Neural circuit and transcriptomic studies and strategies for resilient motor control

Introduction: While it is well known that Parkinson's disease (PD) progressively disrupts the brain's motor circuitry, a key gap in our understanding is how this circuitry is transformed from early prodromal stages of the disease to subsequent clinical diagnosis after the loss of dopamine neurons. Our team uses a suite of molecular, genetic, behavioral, and imaging approaches to explore the novel hypothesis that PD disrupts the 'engrams' or memories of specific movements. Major advances in the treatment of movement disorders have been lacking for over a decade, potentially because evidence suggests the traditional striatal dSPN/iSPN dichotomy does not fully explain the complexity of cortico-striatal circuit contributions to motor control. Specific neural ensembles encode specific actions. Dysfunction of these ensembles, rather than simple pathway imbalance, may contribute to hypokinetic and hyperkinetic symptoms. We reason that preserving motor engrams by making them more resilient to dopamine loss would slow the disruption of motor circuitry and allow PD patients to perform essential daily tasks.