Acute inactivation of the medial forebrain bundle imposes oscillations in the SNr: a challenge for the 6-OHDA model?

It has been recently shown that the substantia nigra pars reticulata (SNr) of 6-hydroxydopamine (6-OHDA)-lesioned rats, under urethane anaesthesia, manifests a prominent low frequency oscillation (LFO) of around 1Hz, synchronized with cortical slow wave activity (SWA). Nevertheless, it is poorly understood whether these electrophysiological alterations are correlated only with severe dopamine depletion or may also play a relevant pathogenetic role in the early stages of the dopamine denervation. Hence, here we recorded SNr single units and electrocorticogram (ECoG) in two models of dopamine denervation: (i) acute dopamine denervated rats, obtained by injection of tetrodotoxin (TTX), (ii) chronic dopamine depleted rats, 2 weeks after 6-OHDA lesioning. Both TTX and 6-OHDA were infused into the medial forebrain bundle (MFB). The acute TTX-mediated dopamine depletion caused a fast developing occurrence of a SNr/ECoG coherence, peaking between 0.48 and 1.22 Hz, parallel with a consistent decrease of firing rate (from 22.61 ± 7.04 to 15.35 ± 9.04 Hz) homolateraly to the infusion. Strikingly, this abnormal 1 Hz synchronization, TTX-mediated was qualitatively similar to the ECoG/SNr synchronization detectable in the 6-OHDA lesioned hemisphere (LH). In addition, TTX infusion in the un-lesioned hemispheres (UH) of 6-OHDA treated rats, produced ECoG/SNr synchronization qualitatively similar to that recordable in the LH. Hence, our data support the proposition that LFO, is tightly correlated to cortex, and represent a critical hallmark of a basal ganglia (BG) failure from the early stages of dopamine denervation.