Project Details
Description
ABSTRACT
During development, neural progenitors divide to produce nascent neurons, which migrate and extend
axons and dendrites. These neurons form synapses with their neighbors and begin to assemble functional
circuits, which mature as synaptic connectivity is refined and additional neurons are integrated into these
circuits. Defects in these assembly processes can result in a broad range of problems, including visual
processing disorders. Protocadherin-17 (Pcdh17) is a homophilic cell adhesion molecule that is important for
collective outgrowth of amygdala axons and to mediate contact-dependent axon growth in vitro, as well as
short-term synaptic plasticity. Our preliminary data show circuit-level defects in the optic tectum of the larval
zebrafish, with a decrease in the proportion of direction selective neurons and an increase of non-selective
neurons. We also provide data showing that neurons of the optic tectum can fasciculate and co-arborize
during circuit formation. We hypothesize that loss of Pcdh17 adhesion results in altered patterns of arbor
growth and synaptogenesis, which degrades the selectivity of neuronal responses. In this
developmental/exploratory R21, we will examine: 1) the developmental trajectory of visual responses in
pcdh17 mutants to better define when and how these responses diverge from wild type larva, and 2) the
developmental trajectories of axonal and dendritic arbor growth and synaptogenesis in wild type and mutant
larvae. These results could reveal a novel cellular mechanism for the assembly of local circuitry and provide
insight into how cellular growth processes govern the maturation of neural responses.
Status | Active |
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Effective start/end date | 09/30/23 → 08/31/25 |
Funding
- National Eye Institute: $433,125.00
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