| First Author | Chen L | Year | 2022 |
| Journal | Elife | Volume | 11 |
| PubMed ID | 35775627 | Mgi Jnum | J:347565 |
| Mgi Id | MGI:7313890 | Doi | 10.7554/eLife.78055 |
| Citation | Chen L, et al. (2022) Synaptic location is a determinant of the detrimental effects of alpha-synuclein pathology to glutamatergic transmission in the basolateral amygdala. Elife 11:e78055 |
| abstractText | The presynaptic protein alpha-synuclein (alphaSyn) has been suggested to be involved in the pathogenesis of Parkinson's disease (PD). In PD, the amygdala is prone to develop insoluble alphaSyn aggregates, and it has been suggested that circuit dysfunction involving the amygdala contributes to the psychiatric symptoms. Yet, how alphaSyn aggregates affect amygdala function is unknown. In this study, we examined alphaSyn in glutamatergic axon terminals and the impact of its aggregation on glutamatergic transmission in the basolateral amygdala (BLA). We found that alphaSyn is primarily present in the vesicular glutamate transporter 1-expressing (vGluT1(+)) terminals in the mouse BLA, which is consistent with higher levels of alphaSyn expression in vGluT1(+) glutamatergic neurons in the cerebral cortex relative to the vGluT2(+) glutamatergic neurons in the thalamus. We found that alphaSyn aggregation selectively decreased the cortico-BLA, but not the thalamo-BLA, transmission; and that cortico-BLA synapses displayed enhanced short-term depression upon repetitive stimulation. In addition, using confocal microscopy, we found that vGluT1(+) axon terminals exhibited decreased levels of soluble alphaSyn, which suggests that lower levels of soluble alphaSyn might underlie the enhanced short-term depression of cortico-BLA synapses. In agreement with this idea, we found that cortico-BLA synaptic depression was also enhanced in alphaSyn knockout mice. In conclusion, both basal and dynamic cortico-BLA transmission were disrupted by abnormal aggregation of alphaSyn and these changes might be relevant to the perturbed cortical control of the amygdala that has been suggested to play a role in psychiatric symptoms in PD. |
