Objective: Abnormal oscillatory activity within the cortico-basal ganglia (BG)-thalamo-cortical circuit has been observed in Parkinsonian state, especially of β and γ bands (βB and γB). Nevertheless, there is lack of information concerning a crucial BG-cortex interface, i.e. the motor thalamus (MTh)-nucleus reticularis thalami (NRT) loop. Therefore, in the present study we investigated MTh and NRT βB (SSN2018) and γB in animal model of Parkinson’s disease (PD).

Background: Peculiar PD motor symptoms, as tremor or bradykinesia, are results of aberrant βB and γB in the cortico-BG-thalamo-cortical circuit. Since these bands could be considered valuable PD biomarkers, it is fundamental to better understand their dysfunction. βB is anti-kinetic, associated with rigidity and bradykinesia (13-30 Hz) and tremor (31-45 Hz), whilst γB is supposed to be mostly pro-kinetic, associated with dyskinesia. Even the opposite role in motor control, both are exaggerated in BG circuit. Surprisingly, there is no evidence of their activity in MTh-NRT loop, despite its key role as hub station for encoding motor information between BG and cortex.

Methods: We investigated the cortical, MTh and NRT low β (Lβ, 13-25 Hz), high β (Hβ, 25-40 Hz) and γ (60-90 Hz). In order to disentangle mechanisms belong to initial and late dopaminergic lack, we performed experiments in acute and chronic dopamine(DA)-denervated rats, by means of tetrodotoxin (TTX) or 6-hydroxydopamine (6-OHDA) infusion into the medial forebrain bundle (MFB), respectively.

Results: We observed that cortical βB and γB are strongly affected by chronic DA depletion, suggesting its involvement in all peculiar motor symptoms, whilst thalamic activities are affected also by acute DA depletion (TTX), meaning for the onset of early thalamic mechanisms basis for later cortical changes. Hence, the MTh βB decreased in acute state, whilst the γB changed in both acute and chronic states. In NRT, LβB decreased in both conditions, whilst Hβ and γB decreased in acute state, increasing then in chronic denervation.

Conclusions: The present results represent the first evidence underlying the crucial role of the MTh-NRT loop in PD. In particular, changes in MTh-NRT underlie thalamic role in acute state, thus leading to later cortical increase. The increase of γB could be considered as a basis for develop of dyskinesia triggered then by L-DOPA. Overall, we posit the MTh-NRT role to potentially consider it as target for new therapies.

References: SSN2018. 20th Swiss Society for Neuroscience Meeting. February 2018, Zurich (Switzerland). Poster H7.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/new-evidence-for-thalamic-dysfunction-in-parkinsonian-rats/