Swain, Alexander
(2019)
INVESTIGATION OF ENHANCING VISUAL SPATIAL ACUITY IN
DEVELOPMENTALLY COMPROMISED CIRCUITS.
Master's Thesis, University of Pittsburgh.
(Unpublished)
Abstract
The development of visual acuity requires visual experience, but the neural mechanisms that
mediate the experience-dependent maturation of visual acuity remain unknown. After eye opening
in mice, visual acuity is very poor but with time and visual experience, matures to an adult-level
by 45 days post-birth (p45). Accumulating evidence demonstrates that the development of visual
acuity requires the maturation of parvalbumin-expressing (PV) inhibitory neurons. Enhancing the
maturation of inhibition accelerates the onset of adult-level visual acuity and the development of
PV neurons, while rearing mice without visual experience delays maturation of inhibition and
holds acuity at a juvenile state. In this study, we chronically perturbed PV inhibitory neurons in
order to assess their direct role in the development of visual acuity by selectively knocking-out
(KO) ErbB4 receptor tyrosine kinase in parvalbumin-expressing cells. ErbB4 is a protein important
for the stabilization of excitatory input onto PV neurons. When ErbB4 is knocked out, excitatory
input fails to stabilize onto PV neurons, resulting in a 25% reduced evoked firing rate. This
phenotype mimics immature PV neurons. We found that adult PV-ErbB4 KO mice had a
behavioral deficit in visual acuity compared to wild type (WT) mice. The difference in visual
acuity between WT and PV-ErbB4 KOs is comparable to the difference between a juvenile p35
mouse and an adult p45 mouse with mature acuity. This is a 10-day developmental difference
between WT and PV-ErbB4 KOs and demonstrates that fully functional, adult-like PV neurons
are required to develop mature visual acuity. We also found that the visual acuity of PV-ErbB4
KOs can be rescued by using a behavioral training task. This is significant because we were able
to bypass the initial deficit, indicating a role for other circuits in the brain involved in regulating
visual acuity in behaviorally relevant environments. We therefore conclude that PV neurons are
necessary for establishing the baseline, mature visual acuity, but with training other circuits may
be involved in improving and enhancing visual acuity.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
|
| Date: |
14 January 2019 |
| Date Type: |
Publication |
| Defense Date: |
18 November 2018 |
| Approval Date: |
14 January 2019 |
| Submission Date: |
11 December 2018 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
42 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Medicine > Integrative Systems Biology |
| Degree: |
MS - Master of Science |
| Thesis Type: |
Master's Thesis |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Vision, Visual Acuity, Inhibition, Parvalbumin, ErbB4 Receptor Tyrosine Kinase, ErbB4, Development |
| Date Deposited: |
14 Jan 2019 15:57 |
| Last Modified: |
14 Jan 2019 15:57 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/35742 |
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