Substantia nigra pars reticulata single unit activity in normal and 60HDA-lesioned rats: Effects of intrastriatal apomorphine and subthalamic lesions

Abstract

The spontaneous activity and the response to intrastriatal application of apomorphine of substantia nigra pars reticulata (SNpr) single units was studied in four experimental groups of rats: (1) normal rats; (2) subthalamic nucleus (STN) lesioned rats; (3) rats bearing a 6-hydroxydopamine (60HDA) lesion; and (4) 60HDA-lesioned animals with an additional STN lesion. Thirty-eight percent of units from 60HDA-lesioned rats showed a bursting pattern of spontaneous activity, which was never found in normal rats. STN lesions had no effect on the spontaneous activity of SNpr units from normal rats, but reduced the percentage of burst units in 60HDA-lesioned animals. Intrastriatal apomorphine produced responses in 62% of SNpr units from normal rats and 85% of units from 60HDA-lesioned animals (P < 0.05). In addition, the modifications in the firing rate and in the coefficient of variation of the interspike intervals induced by intrastriatal apomorphine were significantly greater for the units isolated from 60HDA-lesioned rats. In particular, it was noted that all the burst units responded to apomorphine, showing the highest changes in firing rate and coefficient of variation. However, intrastriatal apomorphine did not always turn the activity of burst units into a more physiological pattern. STN lesions reduced the percentage of units responding to intrastriatal apomorphine in normal rats. In 60HDA-lesioned rats, STN lesions reduced the number of responsive units, and their change in mean firing rate and coefficient of variation. Our results show that the STN participates in the genesis of the bursting pattern of activity of SNpr units in 60HDA-lesioned rats, and that STN lesions can partially revert the abnormal spontaneous and apomorphine-induced responses of SNpr units in these animals.

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

“…Incidence of a bursty firing pattern, mean bursts per 1000 spikes, ISI CV and mean firing rate were significantly larger in the dopamine lesioned than control hemisphere (p<0.05). Results are consistent with previous reports of firing pattern changes in the rodent STN and basal ganglia output nuclei after loss of dopamine from this laboratory (Parr-Brownlie et al, 2007; Walters et al, 2005, 2007) and others (Belluscio et al, 2003, 2007; Breit et al, 2006; Burbaud et al, 1995; Hassani et al, 1996; Hollerman and Grace, 1990; MacLeod et al, 1990; Magill et al, 2001; Murer et al, 1997; Ni et al, 2001; Perier et al, 2000; Rohlfs et al, 1997; Sanderson et al, 1986; Tai et al, 2003; Tseng et al, 2001, 2005; Vila et al, 2000). …”

“…In the anesthetized 6-hydroxydopamine (6-OHDA) rat model of Parkinson’s disease, many inhibitory GABAergic projection neurons in basal ganglia output nuclei exhibit bursty and ~1 Hz oscillatory firing patterns (Belluscio et al, 2003, 2007; Burbaud et al, 1995; MacLeod et al, 1990; Murer et al, 1997; Rohlfs et al, 1997; Sanderson et al, 1986; Tseng et al, 2001, 2005; Walters et al, 2007). Slow wave (~1 Hz) oscillatory activity is prominent in the cortex in urethane anesthetized rats (Steriade et al, 1993a), and this cortical input is critical for expression of slow wave oscillations in the basal ganglia (Magill et al, 2001).…”

Optogenetic activation of nigral inhibitory inputs to motor thalamus in the mouse reveals classic inhibition with little potential for rebound activation

“…This was observed in 2 of 5 cells tested, while the other 3 only showed single spike suppression. It should be noted that the optogenetic light stimulation used here illuminated a large area around the recorded IZ neuron and is therefore likely to simultaneously activate a substantial proportion of all nigral inputs to the cell, a condition not expected to occur in the desynchronized normal state of nigral input in vivo , but possibly more common in the parkinsonian condition where nigral activity has been observed to become more bursty (Murer et al, 1997; Wichmann et al, 1999) and more synchronized between neurons (Avila et al, 2010; Brazhnik et al, 2012). Hence, in mice, LTS rebounds are unlikely to occur in the single-spike mode of thalamic activity as a consequence of desynchronized regular basal ganglia inputs, but may in some cases be triggered by synchronized bursts as observed in parkinsonian conditions.…”

Dissociable effects of dopamine on neuronal firing rate and synchrony in the dorsal striatum

“…Dopamine (DA) transmission within the basal ganglia is essential for the normal expression of spontaneous and voluntary movement (Poirier et al, 1975; Amalric and Koob, 1987; Fletcher and Starr, 1987; Zhou and Palmiter, 1995). Dysfunction of DA transmission has profound consequences upon the function of the basal ganglia, altering downstream activity and motor output (Lloyd, 1977; Filion, 1979; Sanderson et al, 1986; Pan and Walters, 1988; MacLeod et al, 1990; Calabresi et al, 1993; Burbaud et al, 1995; Chesselet and Delfs, 1996; Levy et al, 1997; Murer et al, 1997; Rohlfs et al, 1997; Moore et al, 1998; Ni et al, 2000; Chen et al, 2001; Magill et al, 2001; West and Grace, 2002). Loss of DA projections is the characteristic morphological feature of Parkinson's disease (PD) (Shimohama et al, 2003), wherein degeneration of substantia nigra pars compacta (SNc) projections results in decreased extracellular striatal DA levels (Schober, 2004).…”