Pathological low frequency synchronization of the rat basal ganglia following the TTX-mediated blockade of the medial forebrain bundle: focus on the cortico-STN-GP pathway.

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J Physiol 2009 Jul;

Authors: Salvatore Galati, Paolo Stanzione, Vincenza D'Angelo, Ernesto Fedele, Francesco Marzetti, Teresa Procopio, Alessandro Stefani

Univ Tor Vergata;

Pathological oscillations characterize the firing discharge of different basal ganglia (BG) stations in rat models of Parkinson's disease (PD). Most recent literature focused on the prominence of beta frequency band in awake rats. Yet, in 6-hydroxydopamine (6-OHDA)-lesioned animals, the firing discharge of the globus pallidus (GP) and the substantia nigra reticulata (SNr) are in phase with urethane-induced slow wave cortical activity (SWA). The neuronal basis of this pathological synergy at low frequency is widely debated. In order to understand the role of SN pars compacta (SNc) signaling in the development of pathological synchronization, we performed a pharmacological inactivation of the medial forebrain bundle (MFB) through tetrodotoxin (TTX), which led to a dramatic, but reversible, reduction of the DA content in the striatum. This procedure caused a significant contra-lateral akinesia, detectable as soon as anaesthesia vanished, and lasting about 3-4 hours. We sought to determine the electrophysiological counterpart of this transient Parkinsonian-like hypokinetic syndrome. Hence, we obtained the electrocorticogram (ECoG) and single unit recordings from GP and subthalamus (STN) in normal rats before and after the TTX injection in MFB. Intriguingly, the TTX-mediated inactivation of MFB induced a fast developing coherence between cortex and GP and a significant increase of the cortex/STN synchronization. The intra-GP iontophoretic delivery of haloperidol or the GABA A receptor antagonist bicuculline induced a short term cortex/GP synchronization. Strikingly, STN inactivation by local muscimol reversed both haloperidol- and TTX-mediated coherence between cortex and GP. Our data show that an abnormal cortical/BG synchronization, at low frequency, can be reproduced also without SNc neuronal loss and striatal cytoarchitectonic alterations. In addition, our results, which represent an acute and reversible Parkinsonism based upon impaired cable properties, seem compatible with the interpretation of acute changes of the functional interplay between cortex and the STN-GP pathway as key factor mechanism underlying the fast deep brain stimulation (DBS)-induced acute Off-On transitions.

PMID: 19622605 [PubMed - as supplied by publisher]

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