Neural circuits used in sensory processing must be stable enough to mediate survival-critical behaviors, and yet plastic enough to adapt to a dynamic environment. While great progress has been made in understanding how single synapses adjust response strength, less is known about the mechanisms of circuit-level development and plasticity. In the proposed study, I will use electrophysiology to investigate the connections between the two hemispheres of the Xenopus optic tectum, and their role in circuit plasticity and maturation, both in the course of normal development and in response to injury. These connections are poorly understood, and their contribution to circuit development and plasticity is unknown. The optic tectum is homologous to the mammalian superior colliculus and is critical for processing sensory information from multiple modalities. These intertectal inputs are tectal neurons which extend axons across the commissure to synapse onto tectal neurons in the contralateral hemisphere. In the superior colliculus, it has been proposed that these inputs mediate reciprocal inhibition;however the cellular and circuit-level mechanisms underlying this function are unknown. We have developed a new dissection prep in order to allow us to specifically explore 1) how intertectal inputs develop in Xenopus and how these inputs contribute to circuit formation, 2) how changes in the strength of intertectal input affects retinotectal circuit formation and plasticity and, 3) the remodeling of these inputs, and their contribution to recovery post-injury. These experiments will not only address fundamental questions of how neural circuits are formed and maintained, but will provide crucial information on changes that occur in disease states wherein synaptic connectivity is disrupted, such as schizophrenia, stroke, and traumatic brain injury.

Public Health Relevance

The proposed project will investigate fundamental mechanisms of how convergent synaptic connections within neural networks are formed and maintained. Understanding how these connections are made will inform our ability to treat diseases in which synaptic connectivity is disrupted, such as schizophrenia, autism, and traumatic brain injury.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32NS084749-01
Application #
8595093
Study Section
Special Emphasis Panel (ZRG1-F03A-N (20))
Program Officer
Gnadt, James W
Project Start
2013-07-01
Project End
2016-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
1
Fiscal Year
2013
Total Cost
$49,214
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
781613492
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Gambrill, Abigail C; Faulkner, Regina L; McKeown, Caroline R et al. (2018) Enhanced visual experience rehabilitates the injured brain in Xenopus tadpoles in an NMDAR-dependent manner. J Neurophysiol :
Gambrill, Abigail C; Faulkner, Regina; Cline, Hollis T (2016) Experience-dependent plasticity of excitatory and inhibitory intertectal inputs in Xenopus tadpoles. J Neurophysiol :jn.00611.2016