Parafascicular thalamic nucleus activity in a rat model of Parkinson's disease

Abstract

Parkinson's disease is associated with increased oscillatory firing patterns in basal ganglia output, which are thought to disrupt thalamocortical activity. However, it is unclear how specific thalamic nuclei are affected by these changes in basal ganglia activity. The thalamic parafascicular nucleus (PFN) receives input from basal ganglia output nuclei and directly projects to the subthalamic nucleus (STN), striatum and cortex; thus basal ganglia mediated changes on PFN activity may further impact basal ganglia and cortical functions. To investigate the impact of increased oscillatory activity in basal ganglia output on PFN activity after dopamine cell lesion, PFN single-unit and local field potential activities were recorded in neurologically intact (control) rats and in both non-lesioned and dopamine lesioned hemispheres of unilateral 6-hydroxydopamine lesioned rats anesthetized with urethane. Firing rates were unchanged 1-2 weeks after lesion; however, significantly fewer spontaneously active PFN neurons were evident. Firing pattern assessments after lesion showed a larger proportion of PFN spike trains had 0.3-2.5 Hz oscillatory activity and significantly fewer spike trains exhibited low threshold calcium spike (LTS) bursts. In paired recordings, more PFN-STN spike oscillations were significantly correlated, but as these oscillations were in-phase, results are inconsistent with feedforward control of PFN activity by inhibitory oscillatory basal ganglia output. Furthermore, the decreased incidence of LTS bursts is incompatible with inhibitory basal ganglia output inducing rebound bursting in PFN after dopamine lesion. Together, results show that robust oscillatory activity observed in basal ganglia output nuclei after dopamine cell lesion does not directly drive changes in PFN oscillatory activity.

Pathway-Specific Remodeling of Thalamostriatal Synapses in Parkinsonian Mice

“…Given the reported increase in firing of thalamic CM/Pf neurons in PD models (Jouve et al, 2010; Magnin et al, 2000; Orieux et al, 2000; Parr-Brownlie et al, 2009; Yan et al, 2008), and the decrease in thalamic connectivity with dMSNs after chronic dopamine depletion, we hypothesized that thalamostriatal inputs might be actively contributing to decreased spontaneous motor activity in parkinsonian mice through selective drive of the indirect pathway, relative to the direct pathway. We reasoned that disconnection of this pathway could rescue motor behavior.…”

“…CM/Pf neurons in PD patients and animal models show higher firing rates and increased oscillatory activity (Jouve et al, 2010; Orieux et al, 2000; Parr-Brownlie et al, 2009; Yan et al, 2008). In parkinsonian rats, Pf lesions decrease response latency on a motivational task (Henderson et al, 2005), and Pf DBS rescues sensorimotor neglect (Jouve et al, 2010).…”

Cortico-basal ganglia circuitry: a review of key research and implications for functional connectivity studies of mood and anxiety disorders

“…2) seems ideally constructed to facilitate both feedforward and feedback control and both processes are thought to occur in these networks, for example see (Ryan and Clark 1991;Ryan and Sanders 1994;Haber 2003;Gustafson et al 2006;Calabresi et al 2007). In contrast, one recent study reported evidence inconsistent with feedforward modulation of the parafascicular thalamic nucleus by basal ganglia output (Parr-Brownlie et al 2009). Thus, while these control mechanisms are incompletely understood, there is compelling evidence of both feedback and feedforward functionality within the cortico-basal ganglia circuitry.…”

The effects of nigrostriatal dopamine depletion on the thalamic parafascicular nucleus

“…However, it is possible that the function of PF neurons is compromised by dopamine depletion, although they retain their structural integrity. For example, Parr-Brownlie et al (2009) found that although the firing rate of PF neurons was unchanged in response to 6-OHDA MFB lesions, the number of spontaneously active PF cells was decreased in response to 6-OHDA MFB lesions at 1 to 2 weeks postoperatively. Other groups have reported time dependent changes in the firing rate of PF neurons after nigrostriatal dopamine denervation, with changes observed relatively early after dopamine denervation but then returning to normal within several weeks (Ni et al, 2000; Yan et al, 2008); Yan et al also noted a rebound to an increase in firing rate at five weeks postoperatively.…”