Reduced reach-related modulation of motor thalamus neural activity in a rat model of Parkinson's disease.

Motor thalamus (Mthal) is a key node in the corticobasal ganglia (BG) loop that controls complex, cognitive aspects of movement. In Parkinson's disease (PD), profound alterations in neuronal activity occur in BG nuclei and cortex. Because Mthal is located between these two structures, altered Mthal activity has been assumed to underlie the pathogenesis of PD motor deficits. However, to date, inconsistent changes in neuronal firing rate and pattern have been reported in parkinsonian animals. Moreover, although a distinct firing pattern of Mthal neurons, called low-threshold calcium spike bursts (LTS bursts), is observed in reduced preparations, it remains unknown whether they occur or what their role might be in behaving animals. We recorded Mthal spiking activity in control and unilateral 6-hydroxydopamine lesioned rats performing a skilled forelimb-reaching task. We show for the first time that Mthal firing rate in control rats is modulated in a temporally precise pattern during reach-to-grasp movements, with a peak at the time of the reach-end and troughs just before and after it. We identified LTS-like events on the basis of LTS burst characteristics. These were rare, but also modulated, decreasing in incidence just after reach-end. The inhibitory modulations in firing rate and LTS-like events were abolished in parkinsonian rats. These data confirm that nigrostriatal dopamine depletion is accompanied by profound and specific deficits in movement-related Mthal activity. These changes would severely impair Mthal contributions to motor program development in motor cortex and are likely to be an important factor underlying the movement deficits of PD.

Oscillatory waveform sharpness asymmetry changes in motor thalamus and motor cortex in a rat model of Parkinson's disease.

Parkinson's disease (PD) causes bursty and oscillatory activity in basal ganglia output that is thought to contribute to movement deficits through impact on motor thalamus and motor cortex (MCx). We examined the effect of dopamine loss on motor thalamus and motor cortex activity by recording neuronal and LFP activities in ventroanterior-ventrolateral (VAVL) thalamus and MCx in urethane-anesthetised control and parkinsonian rats. Dopamine lesion decreased the firing rate and increased the bursting of putative pyramidal neurons in layer V, but not layer VI, of the MCx without changing other aspects of firing pattern. In contrast, dopamine lesion did not affect VAVL firing rate, pattern or low threshold calcium spike bursts. Slow-wave (~1 Hz) oscillations in LFP recordings were analyzed with conventional power and waveform shape analyses. While dopamine lesion did not influence total power, it was consistently associated with an increase in oscillatory waveform sharpness asymmetry (i.e., sharper troughs vs. peaks) in both motor thalamus and MCx. Furthermore, we found that measures of sharpness asymmetry were positively correlated in paired motor thalamus-MCx recordings, and that correlation coefficients were larger in dopamine lesioned rats. These data support the idea that dysfunctional MCx activity in parkinsonism emerges from subsets of cell groups (e.g. layer V pyramidal neurons) and is evident in the shape but not absolute power of slow-wave oscillations. Hypoactive layer V pyramidal neuron firing in dopamine lesioned rats is unlikely to be driven by VAVL thalamus and may, therefore, reflect the loss of mesocortical dopaminergic afferents and/or changes in intrinsic excitability.