Dopamine D1/5 Receptor Modulation of Excitatory Neurotransmission and Synaptic Plasticity
| dc.contributor.advisor | Greene, Robert W. | en |
| dc.creator | Leverich, Leah Schaal | en |
| dc.date.accessioned | 2010-07-12T18:14:17Z | |
| dc.date.available | 2010-07-12T18:14:17Z | |
| dc.date.issued | 2009-06-18 | |
| dc.description.abstract | Dopamine D1/5 receptor (D1/5R) activation modulates glutamate-dependent neuroplasticity thought to underlie learning and memory. Disturbances in dopamine-glutamate signaling have been implicated in neuropsychiatric disorders such as schizophrenia and addiction. Despite its importance, a mechanism responsible for D1/5R modulation of glutamate-dependent neuroplasticity remains unknown. Here we present evidence using field potential recordings from hippocampal slices showing that D1/5R activation establishes a prolonged temporal window for the induction of NMDA receptor-dependent synaptic plasticity. We found that D1/5R activation increases synaptic responses and long-term potentiation (LTP) expression through a pathway involving NR2B-NMDARs, PKA, PKC, PKM zeta, and src-family tyrosine kinases. D1/5R activation produced sustained increases in the surface expression of NR2B and GluR1 subunits in hippocampal slices, and this increase required the activity of NR2B-NMDARs. Consistent with our field potential recordings, D1/5R activation during memory consolidation facilitates extinction learning to conditioned fear, providing functional relevance for a prolonged window of synaptic potentiation ediated by D1/5Rs at the level of behavioral output. | en |
| dc.format.digitalOrigin | born digital | en |
| dc.format.medium | Electronic | en |
| dc.format.mimetype | application/pdf | en |
| dc.identifier.oclc | 754616918 | |
| dc.identifier.uri | https://hdl.handle.net/2152.5/487 | |
| dc.language.iso | en | en |
| dc.subject | Receptors, Dopamine | en |
| dc.subject | N-Methylaspartate | en |
| dc.subject | Learning | en |
| dc.title | Dopamine D1/5 Receptor Modulation of Excitatory Neurotransmission and Synaptic Plasticity | en |
| dc.type | Thesis | en |
| dc.type.genre | dissertation | en |
| dc.type.material | Text | en |
| thesis.date.available | 2011-06-18 | |
| thesis.degree.department | Graduate School of Biomedical Sciences | en |
| thesis.degree.discipline | Neuroscience | en |
| thesis.degree.grantor | UT Southwestern Medical Center | en |
| thesis.degree.level | Doctoral | en |
| thesis.degree.name | Doctor of Philosophy | en |