Biophysical and functional characterization of VGLUT1-mediated glutamatergic neurotransmission in the substantia nigra
| dc.contributor.author | Akhavan, Adeeb | |
| dc.contributor.supervisor | Nashmi, Raad | |
| dc.date.accessioned | 2026-05-28T19:17:09Z | |
| dc.date.available | 2026-05-28T19:17:09Z | |
| dc.date.issued | 2026 | |
| dc.degree.department | School of Medical Sciences | |
| dc.degree.level | Master of Science MSc | |
| dc.description.abstract | The substantia nigra (SN) is a critical component of basal ganglia circuitry and plays an important role in regulating voluntary movement. It consists of two major subregions, the substantia nigra pars compacta (SNc) and substantia nigra pars reticulata (SNr). Degeneration of dopaminergic (DA) neurons in the SNc disrupts basal ganglia circuitry and contributes to the motor deficits seen in Parkinson’s disease. Neurons in the SN receive synaptic input from several neurotransmitter systems, including glutamate. However, the synaptic properties of glutamatergic inputs into the SN, as well as their influence on neuronal activity within the SN, remain incompletely understood. In this study, we examined glutamatergic synaptic transmission mediated by VGLUT1-expressing inputs to SN neurons. Using a VGLUT1-Cre::ChR2 mouse line, VGLUT1-expressing presynaptic fibers were optogenetically stimulated while whole-cell patch clamp recordings were obtained from SNc DA neurons and SNr GABAergic neurons in acute brain slices. Pharmacological experiments using DNQX and APV demonstrated that excitatory postsynaptic currents in both SNc DA neurons and SNr GABAergic neurons were mediated by AMPA and NMDA receptors. Application of tetrodotoxin (TTX) and 4-aminopyridine (4-AP) confirmed that these responses were action potential dependent and monosynaptic. Short-term plasticity was examined using five pulse stimulus trains delivered at 5 Hz and 25 Hz. Overall, VGLUT1-expressing inputs exhibited predominantly depressing short-term plasticity profiles in both the SNc and the SNr, however, a range of plasticity patterns were seen, including facilitation and mixed plasticity. Depressive effects were significantly stronger during 25 Hz stimulation compared to 5 Hz stimulation for both AMPA- and NMDA-mediated responses in both regions. Response latency was significantly shorter in SNr neurons than in SNc neurons, although AMPA and NMDA receptor rise and decay kinetics were otherwise similar between regions. No significant differences in short-term plasticity were observed between SNc and SNr neurons or between AMPA- and NMDA-mediated components within either region. These results provide further insight into the synaptic properties of excitatory inputs into the SN and may help inform future studies investigating how glutamatergic signaling within this region contributes to basal ganglia function and dysfunction, including mechanisms that may be relevant for neurological disorders such as Parkinson’s disease. | |
| dc.description.embargo | 2027-05-01 | |
| dc.description.scholarlevel | Graduate | |
| dc.identifier.uri | https://hdl.handle.net/1828/23952 | |
| dc.language | English | eng |
| dc.language.iso | en | |
| dc.rights | Available to the World Wide Web | |
| dc.subject | whole-cell patch-clamp electrophysiology | |
| dc.subject | substantia nigra | |
| dc.subject | short term plasticity | |
| dc.subject | glutamate | |
| dc.subject | dopamine | |
| dc.subject | parkinson's disease | |
| dc.subject | gaba | |
| dc.subject | optogenetics | |
| dc.subject | basal ganglia | |
| dc.title | Biophysical and functional characterization of VGLUT1-mediated glutamatergic neurotransmission in the substantia nigra | |
| dc.type | Thesis |