Parkinson disease (PD) is the second most prevalent neurodegenerative disorder and characterized the selective degeneration of vulnerable neuron populations, prominently among them, dopamine (DA) neurons in the substantia nigra (SN). It is currently unclear to what degree surviving DA SN neurons either homeostatically adapt their activity during PD to compensate for reduced population size and dopamine depletion, or enter a functionally impaired state even before degeneration. To study the long-term temporal profile of post-lesional adaptations of the nigrostriatal DA system, we utilized a unilateral partial 6-hydroxydopamine (6-OHDA) model. By monitoring spontaneous motor behavior of the 6-OHDA and ACSF-infused control mice for 3 month post-surgery, we identified two distinct phases. As expected, the 6-OHDA infused mice displayed a strong contralateral turning deficit compared to ACSF-infused mice during the first few weeks (impaired phase). However, over the course of 2 months this turning deficit completely disappeared (recovered phase). To compare the functional activities of surviving DA SN neurons during these two behavioral states, we carried out in vivo single unit extracellular recordings combined with juxtacellular labelling for immunohistochemical und morphological characterization. By focusing on the medial SN, we found that the firing frequencies and patterns of surviving DA neurons recorded during the recovered phase were not significantly different from DA SN neurons from ACSF-infused controls. In contrast, the activity of DA SN neurons from 6-OHDA infused mice recorded during the earlier impaired phase, displayed a significant 7-fold reduction in burst rate (control: 0.31 ± 0.14, n=9; 6-OHDA: 0.04Hz ± 0.02, n=9), while their mean frequency of firing was not affected (control: 5.4Hz ± 0.51, n=9; 6-OHDA: 4.13Hz ± 0.59, n=9). We are currently investigating the possibility of a causal role of the temporary reduction of burst rate in surviving DA SN neurons for the impaired turning behavior.
Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, C089
Oral Communications: Transient impairment of in vivo burst firing in surviving dopamine neurons is associated with a temporary motor deficit after partial lesion
L. Kovacheva1, N. Farassat1, K. M. Costa1,2,3, J. Roeper1
1. Institute for Neurophysiology, Frankfurt am Main, Hessen, Germany. 2. Max Planck Institute for Brain Research, Frankfurt am Main, Germany. 3. National Institute on Drug abuse, Baltimore, Maryland, United States.
View other abstracts by:
Where applicable, experiments conform with Society ethical requirements.