Jill's research is aimed at dissecting molecular mechanisms that influence our choice of motor behaviors. Motivation to initiate specific actions and simultaneously inhibit inappropriate motor movements is dependent on signaling through the basal ganglia, a group of brain nuclei that integrate incoming information from other brain regions that sense the environment, mood, and past experience. Input to the basal ganglia is mostly via the striatum, a large subcortical structure that receives excitatory inputs from all areas of the neocortex. The striatum is enriched in various neurochemicals, such as dopamine, acetylcholine, opioids and endocannabinoids, which all signal through cell-surface receptors to modulate excitatory inputs and motor behaviors. Such neuromodulation is thought to enhance our ability to optimize complex motor behaviors.
Disruption of signaling through basal ganglia nuclei can have both motoric and psychological consequences. For example, in Huntington’s disease the death of striatal neurons that project to downstream basal ganglia nuclei is correlated with uncontrollable motor movements, compulsive behaviors, and mood disturbances. In Parkinson’s disease, degeneration of the dopaminergic inputs to the striatum results in the loss of voluntary movement and motivation, and an increased risk of depression. By contrast, drugs of abuse over-stimulate the dopaminergic system, which can elevate mood and drive hyperactivity and compulsive behaviors (including the habit-forming aspect of drug abuse).
To understand neural mechanisms that regulate motor behavior, we use genetic engineering in mice that allows specific subtypes of brains cells and their connections to be visualized, isolated for analysis, molecularly controlled, and recorded. We also use mouse models to mimic disease-causing mutations in humans. By intercrossing these different types of transgenic mice, we can better understand how motor diseases impact the function of brain cells, and how we might mitigate symptoms.
We have focused expertise on a striatal cell subtype in clusters called striosomes. Striosomal neurons have unusually dense synaptic contacts onto a subset of dopaminergic neurons that are thought to be particularly vulnerable in Parkinson’s disease. An imbalance in striosomal activity, relative to the surrounding striatal matrix, is associated with several movement disorders, including L-DOPA-induced dyskinesias, Huntington's disease, dystonia and drug addiction. These diseases share features of abnormally repetitive behaviors and mood disturbances. We are working to identify genes that are dysregulated in these movement disorders and whether selective modulation of striosome or matrix compartment signaling can ameliorate symptoms in animal models.
Jill's CV - Click Here
Email: jrc@mit.edu
Disruption of signaling through basal ganglia nuclei can have both motoric and psychological consequences. For example, in Huntington’s disease the death of striatal neurons that project to downstream basal ganglia nuclei is correlated with uncontrollable motor movements, compulsive behaviors, and mood disturbances. In Parkinson’s disease, degeneration of the dopaminergic inputs to the striatum results in the loss of voluntary movement and motivation, and an increased risk of depression. By contrast, drugs of abuse over-stimulate the dopaminergic system, which can elevate mood and drive hyperactivity and compulsive behaviors (including the habit-forming aspect of drug abuse).
To understand neural mechanisms that regulate motor behavior, we use genetic engineering in mice that allows specific subtypes of brains cells and their connections to be visualized, isolated for analysis, molecularly controlled, and recorded. We also use mouse models to mimic disease-causing mutations in humans. By intercrossing these different types of transgenic mice, we can better understand how motor diseases impact the function of brain cells, and how we might mitigate symptoms.
We have focused expertise on a striatal cell subtype in clusters called striosomes. Striosomal neurons have unusually dense synaptic contacts onto a subset of dopaminergic neurons that are thought to be particularly vulnerable in Parkinson’s disease. An imbalance in striosomal activity, relative to the surrounding striatal matrix, is associated with several movement disorders, including L-DOPA-induced dyskinesias, Huntington's disease, dystonia and drug addiction. These diseases share features of abnormally repetitive behaviors and mood disturbances. We are working to identify genes that are dysregulated in these movement disorders and whether selective modulation of striosome or matrix compartment signaling can ameliorate symptoms in animal models.
Jill's CV - Click Here
Email: jrc@mit.edu