Cortical Slow Oscillatory Activity Is Reflected in the Membrane Potential and Spike Trains of Striatal Neurons in Rats with Chronic Nigrostriatal Lesions

Abstract

Neurons in the basal ganglia output nuclei display rhythmic burst firing after chronic nigrostriatal lesions. The thalamocortical network is a strong endogenous generator of oscillatory activity, and the striatum receives a massive projection from the cerebral cortex. Actually, the membrane potential of striatal projection neurons displays periodic shifts between a very negative resting potential (down state) and depolarizing plateaus (up states) during which they can fire action potentials. We hypothesized that an increased excitability of striatal neurons may allow transmission of cortical slow rhythms through the striatum to the remaining basal ganglia in experimental parkinsonism. In vivo intracellular recordings revealed that striatal projection neurons from rats with chronic nigrostriatal lesions had a more depolarized membrane potential during both the down and up states and an increased firing probability during the up events. Furthermore, lesioned rats had significantly fewer silent neurons than control rats. Simultaneous recordings of the frontal electrocorticogram and membrane potential of striatal projection neurons revealed that the signals were oscillating synchronously in the frequency range 0.4-2 Hz, both in control rats and rats with chronic nigrostriatal lesions. Spreading of the slow cortical rhythm is limited by the very low firing probability of control rat neurons, but a slow oscillation is well reflected in spike trains of ϳ60% of lesioned rat neurons. These findings provide in vivo evidence for a role of dopamine in controlling the flow of cortical activity through the striatum 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

“…Striatal firing rate in the lesioned hemisphere was 2.4 times greater than in intact rats (Table 1). These observations are consistent with intracellular recording studies (Tseng et al, 2001b) that demonstrated striatal neurons have more depolarized membrane potentials during both the down-states and up-states and fire more spikes per up-state after dopamine cell lesion.Striatal spike-SNpr LFP phase relationships-When striatal activity was recorded in the lesioned hemisphere in conjunction with SNpr LFP recordings ( Fig. 3C; n=6), spectral analysis of striatal firing rate slow oscillations showed peak frequencies (mean main peak: 1.0 ± 0.2 Hz) similar to peak frequencies of SNpr LFP oscillations (mean main peak: 1.0 ± 0.2 Hz).…”

“…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.…”

“…Murer, Tseng and coworkers have shown that striatal neurons are more depolarized after dopamine cell lesion and fire more frequently in conjunction with the slow oscillations that are prominent in cortical EEG in anesthetized rats (Tseng et al, 2001b). 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.…”

“…In anesthetized rats, this synchronized activity has a periodicity of ∼1 Hz. As this oscillatory activity is relatively stable in the cortex over time, it can be viewed as a probe or input signal for assessing the effects of dopamine loss on passage of slow oscillatory activity through the basal ganglia.Murer, Tseng and coworkers have shown that striatal neurons are more depolarized after dopamine cell lesion and fire more frequently in conjunction with the slow oscillations that are prominent in cortical EEG in anesthetized rats (Tseng et al, 2001b). 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.…”

Deep Brain Stimulation for Movement Disorders of Basal Ganglia Origin: Restoring Function or Functionality?

“…Among these, the effects of dopamine on striatal transmission play a central role in all models of basal ganglia function and in the proposed pathophysiologic mechanisms in both PD and dystonia. Dopamine is released in the striatum and other nodes of the motor circuit from terminals of projections from the substantia nigra pars compacta, and regulates the activity of the basal ganglia output neurons by facilitating corticostriatal transmission upon MSNs of the direct pathway and inhibiting corticostriatal transmission upon MSNs of the indirect pathway ( [99][100][101][102]; Fig. 1).…”