Spreading of slow cortical rhythms to the basal ganglia output nuclei in rats with nigrostriatal lesions

Abstract

A high proportion of neurons in the basal ganglia display rhythmic burst firing after chronic nigrostriatal lesions. For instance, the periodic bursts exhibited by certain striatal and subthalamic nucleus neurons in 6-hydroxydopamine-lesioned rats seem to be driven by the approximately 1 Hz high-amplitude rhythm that is prevalent in the cerebral cortex of anaesthetized animals. Because the striatum and subthalamic nucleus are the main afferent structures of the substantia nigra pars reticulata, we examined the possibility that the low-frequency modulations (periodic bursts) that are evident in approximately 50% nigral pars reticulata neurons in the parkinsonian condition were also coupled to this slow cortical rhythm. By recording the frontal cortex field potential simultaneously with single-unit activity in the substantia nigra pars reticulata of anaesthetized rats, we proved the following. (i) The firing of nigral pars reticulata units from sham-lesioned rats is not coupled to the approximately 1 Hz frontal cortex slow oscillation. (ii) Approximately 50% nigral pars reticulata units from 6-hydroxydopamine-lesioned rats oscillate synchronously with the approximately 1 Hz cortical rhythm, with the cortex leading the substantia nigra by approximately 55 ms; the remaining approximately 50% nigral pars reticulata units behave as the units recorded from sham-lesioned rats. (iii) Periodic bursting in nigral pars reticulata units from 6-hydroxydopamine-lesioned rats is disrupted by episodes of desynchronization of cortical field potential activity. Our results strongly support that nigrostriatal lesions promote the spreading of low-frequency cortical rhythms to the substantia nigra pars reticulata and may be of outstanding relevance for understanding the pathophysiology of Parkinson's disease.

Phase relationships support a role for coordinated activity in the indirect pathway in organizing slow oscillations in basal ganglia output after loss of dopamine

“…In the context of the familiar dual circuit model of the basal ganglia (Albin et al, 1989;Alexander and Crutcher, 1990;DeLong, 1990), the present results argue that activity in the indirect pathway from the striatum to the SNpr via the GP and STN plays a more prominent role than the direct pathway in establishing slow oscillatory activity in the basal ganglia output nuclei after loss of dopamine. On the other hand, only 30-50% of the SNpr neurons are showing significant oscillations in the present study, a proportion consistent with other studies examining SNpr activity in the anesthetized dopamine cell lesioned preparation (Sanderson et al, 1986;Burbaud et al, 1995;Murer et al, 1997;Rohlfs et al, 1997;Tseng et al, 2000Tseng et al, , 2001aBelluscio et al, 2003). The observation that this proportion is considerably smaller than the proportion showing oscillatory activity in other areas of the basal ganglia suggests that the direct pathway is exerting a relatively greater influence, and counteracting the effect of the indirect pathway, on those SNpr neurons that fail to show oscillatory activity in the lesioned rats.…”

“…Firing rates of neurons recorded in the SNpr of the two preparations were not significantly different (Table 1), despite the marked difference in firing pattern after dopamine loss. These observations are consistent with a number of studies showing increased burstiness or oscillatory activity in the SNpr 2-8 weeks after dopamine cell lesion in anesthetized rats (Sanderson et al, 1986;MacLeod et al, 1990;Burbaud et al, 1995;Murer et al, 1997;Rohlfs et al, 1997;Tseng et al, 2000Tseng et al, ,2001aBelluscio et al, 2003).…”

“…Mean firing rates were significantly increased in the STN and the striatum but not significantly altered in the GP and SNpr at this post lesion time point. In general, the firing pattern changes observed are consistent with previous reports of alterations in individual basal ganglia nuclei in anesthetized, dopamine-depleted preparations at time periods 1-10 weeks after lesion (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, 2000Magill et al, , 2001Ni et al, 2000aNi et al, , 2001Tseng et al, 2000Tseng et al, , 2001aVila et al, 2000;Belluscio et al, 2003;Tai et al, 2003). It is interesting to note that dopamine receptor antagonist-induced reductions in dopamine receptor stimulation also induce changes in firing pattern in basal ganglia output nuclei in anesthetized rats (Degos et al, 2005).…”

“…In one commonly used animal model of PD, the anesthetized rodent with a unilateral 6-hydroxydopamine (6-OHDA)-induced medial forebrain bundle lesion, a number of studies have found that firing patterns in STN and SNpr become more bursty (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, , 2001aVila et al, 2000;Magill et al, 2001;Ni et al, 2001;Belluscio et al, 2003;Tai et al, 2003). This bursty activity has been shown to be correlated with slow oscillations in cortical EEG (Magill et al, 2001;Tseng et al, 2001b;Belluscio et al, 2003). While one must be cautious about generalizing from results obtained in anesthetized preparations, these preparations have a property that is useful for probing changes in network function.…”

“…This raises the possibility that the altered firing patterns observed in basal ganglia output nuclei after dopamine cell lesion are due to increased activity in the striatum, transmitted through the direct or indirect pathways to the SNpr. Other studies have stressed the importance of cortical or other input to the STN, and/or local changes in the STN in mediating changes in firing patterns in the external segment of the globus pallidus (GP) and the SNpr after loss of dopamine (Magill et al, 2001;Tseng et al, 2001b;Murer et al, 2002;Belluscio et al, 2003). Information about phase relationships of the oscillatory activity emerging in these nuclei could provide insight into how firing pattern changes in the striatum, GP, and STN are interrelated and contribute to changes in the basal ganglia output nuclei.…”