Nigrostriatal lesion induces D2‐modulated phase‐locked activity in the basal ganglia of rats

Abstract

There is a debate as to what modifications of neuronal activity underlie the clinical manifestations of Parkinson's disease and the efficacy of antiparkinsonian pharmacotherapy. Previous studies suggest that release of GABAergic striatopallidal neurons from D2 receptor-mediated inhibition allows spreading of cortical rhythms to the globus pallidus (GP) in rats with 6-hydroxydopamine-induced nigrostriatal lesions. Here this abnormal spreading was thoroughly investigated. In control urethane-anaesthetized rats most GP neurons were excited during the active part of cortical slow waves ('direct-phase' neurons). Two neuronal populations having opposite phase relationships with cortical and striatal activity coexisted in the GP of 6-hydroxydopamine-lesioned rats. 'Inverse-phase' GP units exhibited reduced firing coupled to striatal activation during slow waves, suggesting that this GP oscillation was driven by striatopallidal hyperactivity. Half of the pallidonigral neurons identified by antidromic stimulation exhibited inverse-phase activity. Therefore, spreading of inverse-phase oscillations through pallidonigral axons might contribute to the abnormal direct-phase cortical entrainment of basal ganglia output described previously. Systemic administration of the D2 agonist quinpirole to 6-hydroxydopamine-lesioned rats reduced GP inverse-phase coupling with slow waves, and this effect was reversed by the D2 antagonist eticlopride. Because striatopallidal hyperactivity was only slightly reduced by quinpirole, other mechanisms might have contributed to the effect of quinpirole on GP oscillations. These results suggest that antiparkinsonian efficacy may rely on other actions of D2 agonists on basal ganglia activity. However, abnormal slow rhythms may promote enduring changes in functional connectivity along the striatopallidal axis, contributing to D2 agonist-resistant clinical signs of parkinsonism.

Altered neuronal activity relationships between the pedunculopontine nucleus and motor cortex in a rodent model of Parkinson's disease

“…Consistent with this phenomenon, increases in burstiness and oscillatory activity have been shown in spike trains of several basal ganglia nuclei following dopamine cell lesion in the anesthetized rat model of PD (Sanderson et al, 1986;MacLeod et al, 1990;Hollerman and Grace, 1992;Burbaud et al, 1995;Hassani et al, 1996;Murer et al, 1997;Rohlfs et al, 1997;Magill et al, 2000;Tseng et al, 2000Tseng et al, , 2001aPerier et al, 2000;Vila et al, 2000;Ni et al, 2001;Belluscio et al, 2003;Tai et al, 2003;Walters et al, 2005Walters et al, , 2007Parr-Brownlie et al, 2007;Zold et al, 2007).…”

“…The effect of dopamine cell lesion on PPN and MCx LFP activity-Slow ∼1 Hz oscillations that emerge in LFP and spike trains in the basal ganglia of urethane-anesthetized rats after dopamine cell lesion have been shown to be highly coherent with slow oscillations in cortical activity (Magill et al, 2001;Tseng et al, 2001b;Belluscio et al, 2003;ParrBrownlie et al, 2007;Walters et al, 2007;Zold et al, 2007). In the present study, PPN LFPs were significantly coherent with MCx LFPs in the ∼1 Hz range (0.3-2.5 Hz) in intact rats (0.65 ± 0.03, n=10 rats) and lesioned rats (0.52 ± 0.06, n=11 rats) ( Fig.…”

“…Cortical activity in the urethane-anesthetised rat is highly synchronized, characteristically oscillates at ∼1Hz, and is relatively stable over time (Steriade et al, 1993;Steriade, 1995, 1997;Amzica and Steriade, 1998). Many studies have shown changes in firing pattern and increased oscillatory activity in the basal ganglia following dopamine cell lesion in the anesthetized rat (Sanderson et al, 1986;MacLeod et al, 1990;Hollerman and Grace, 1992;Burbaud et al, 1995;Hassani et al, 1996;Murer et al, 1997;Rohlfs et al, 1997;Tseng et al, 2000Tseng et al, , 2001aTseng et al, , 2001bPerier et al, 2000;Vila et al, 2000;Magill et al, 2001;Ni et al, 2001;Belluscio et al, 2003;Tai et al, 2003;Walters et al, 2005Walters et al, , 2007Parr-Brownlie et al, 2007;Zold et al, 2007). Recently, this cortical oscillatory activity has been used as a probe signal in the urethane-anesthetized rat to investigate the effects of dopamine loss on the phase relationships between oscillatory activity in the external segment of the globus pallidus (GPe), the substantia nigra pars reticulata (SNpr), the subthalamic nucleus (STN), and the striatum .…”

Power Fluctuations in Beta and Gamma Frequencies in Rat Globus Pallidus: Association with Specific Phases of Slow Oscillations and Differential Modulation by Dopamine D1and D2Receptors

“…Some previous data showing enhanced coherence at gamma frequencies between GP and other structures in anesthetized rats (but during periods of cortical activation considered physiologically similar to the awake state) also support a local component to LFP signals recorded in GP (Magill et al, 2004;Sharott et al, 2005). There is also considerable evidence for expression of anesthetic-induced slow-wave activity in rat GP (Magill et al, 2004;Walters et al, 2007;Zold et al, 2007). How the local rhythms are generated remains uncertain, but cocultures of GP and STN neurons form networks that show intrinsic slow oscillations (Plenz and Kital, 1999), suggesting that basal ganglia networks including GP have the necessary machinery to generate such rhythms, and modeling studies indicate that the properties of the intact GP-STN network would support oscillations in both the beta (Holgado et al, 2010) and gamma (Humphries et al, 2006) ranges.…”

NMDA Receptor Gating of Information Flow through the StriatumIn Vivo

“…All methods including signal analysis were similar to those described previously (Tseng et al, 2001;Kasanetz et al, 2006;Belluscio et al, 2007;Zold et al, 2007;Kasanetz et al, 2008). Recordings were performed under urethane anesthesia [1.2 g/kg i.p.…”