A major challenge in neuroscience research is to identify the precise functional neural circuits that are responsible for diverse nervous system processes such as sensory perception, learning and memory, as well as the aberrant circuits that underline the pathological conditions such as chronic pain, depression, addiction, and epilepsy. Previous work in this area has focused on designing molecular sensors that detect transient voltage change or calcium influx using optical methods. However, the use of these sensors for studying in vivo complex neural physiology, and pathophysiology processes of the mammalian nervous system have been extremely limited. Moreover, these sensors do not allow for anatomical re-construction of the activated circuits. In this EUREKA application, we propose to develop novel genetically encoded anatomical probes for visualizing neuronal activity and plasticity directly. These probes will label activated neurons and synapses (and those most likely undergo plasticity) with a marker (e.g. a fluorescent protein) for easy histological detection and anatomical tracing. The chief principle underlying this unconventional design of probes is to use activity (strong calcium influx) to induce the translation of an otherwise un-translated marker protein. Successful development of the activity-induced anatomical probes will greatly advance our understanding of the functions and dysfunctions of the nervous system.

Public Health Relevance

Neuronal plasticity is essential for diverse nervous system functions such as sensory perception, learning and memory. It is also a major component of pathological changes leading to diseases such as chronic pain, depression, addiction, and epilepsy. In this proposal, we will develop genetically encoded anatomical probes for visualizing neuronal activity and plasticity. These probes will greatly help us identify the aberrant circuits and plasticity underlying many neurological and mental disorders, providing the basis for future therapeutic interventions.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA028302-04
Application #
8267117
Study Section
Special Emphasis Panel (ZMH1-ERB-L (05))
Program Officer
Pollock, Jonathan D
Project Start
2009-07-01
Project End
2013-07-31
Budget Start
2012-06-01
Budget End
2013-07-31
Support Year
4
Fiscal Year
2012
Total Cost
$299,614
Indirect Cost
$107,554
Name
Duke University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
Nelson, Anders; Schneider, David M; Takatoh, Jun et al. (2013) A circuit for motor cortical modulation of auditory cortical activity. J Neurosci 33:14342-53
Takatoh, Jun; Nelson, Anders; Zhou, Xiang et al. (2013) New modules are added to vibrissal premotor circuitry with the emergence of exploratory whisking. Neuron 77:346-60