Much progress has been made in our understanding of the genetic and molecular factors underlying autism, and how they affect structural and electrophysiological properties of single neurons and the synapses between them. Yet how these changes impact neural circuit function, and ultimately behavior, has been more difficult to discern.
To address this question, Bence Ölveczky and his colleagues plan to use and continue to refine high-resolution kinematic tracking technology that measures behavior of freely behaving rats in 3-D at unprecedented spatio-temporal resolution continuously over weeks-long timescales1. An analysis pipeline will be developed to pinpoint aspects of behavioral organization and motor control that are affected in rat models of autism, including deviations from normal movement kinematics, motor sequencing and longer-term behavioral patterning. For this grant, the group plans to study Fmr1 knockout (a model of fragile X syndrome) rats.
To get at the neural circuit-level origins of autism-related behavioral and motor control deficits, the sophisticated behavioral tracking system will be combined with long-term continuous neural recordings2. Recordings will be made from large populations of single neurons in motor-related parts of the striatum, a structure widely implicated in many forms of autism. These large and unique neural and behavioral data streams will be analyzed to shed light on how neural coding schemes in the striatum, and striatal dynamics more generally, are altered in a fragile X rat model.
The project extends ongoing work in the Ölveczky lab and takes advantage of existing expertise, infrastructure and analysis frameworks. It is expected to inspire new hypotheses relating to how changes in basal ganglia circuit dynamics underlie motor-related manifestations of autism, findings that will inform and motivate future research programs into the neural basis of autism-related behavioral phenotypes.
- Deep phenotyping of genetic mouse models of autism
- Novel technology for behavioral phenotyping of autism mouse models
- Linking circuit dynamics and behavior in a rat model of autism
- Biased spatiotemporal dynamics of striatal circuits impact behavior in autism
- Dissecting striatal circuit dynamics during repetitive behaviors in autism