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Cerebellar cortical interneurones. (ai) Spontaneous activity of a molecular layer interneurone. Lower panel shows ten superimposed spikes at an expanded time base. (aii) Interspike interval distribution of molecular layer interneurone activity. (aiii) Population histogram of mean firing rates of molecular layer interneurones (n = 13) (aiv) Autocorrelogram of molecular layer interneurone spontaneous activity. (bi) Spontaneous activity of a putativeGolgi cell. Lower panel shows ten superimposed spikes at an expanded time base. (bii) Interspike interval distribution of Golgi cell activity. (biii) Population histogram of mean firing rates of Golgi cells (n = 6). (biv) Autocorrelogram of Golgi cell spontaneous activity. CV coefficient of variation
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In the present study, a non-pulsatile arterially perfused hindbrain and upper body rat preparation is described which is an extension of the brainstem preparation reported by Potts et al., (Brain Res Bull 53(1):59-67), 1. The modified in situ preparation allows study of cerebellar function whilst preserving the integrity of many of its interconnect...
Citations
Rate and temporal coding in Purkinje cells (PC), the sole output of the cerebellar cortex, play a major role in motor control. PC receives excitatory inputs from granule cells (GC) which also provide feedforward inhibition on PC through the activation of molecular layer interneurons (MLI). In this thesis, I studied the influence of the combined action of excitation/inhibition (E/I) balance and short-term plasticity of GC-MLI-PC synapses on PC discharge, by using electrophysiological recordings, optogenetic stimulation and modelling. This work demonstrates that E/I balances are not equalized in the cerebellar cortex and showed a wide distribution of PC discharge modulation in response to GC inputs, from an increase to a shut down of the discharge. The number of stims in GC bursts strongly controls the strength and sign of PC modulation. Lastly, the interplay between short-term plasticity and E/I balance implements complex but reproducible output patterns of PC responses to GC inputs that should play a key role in stimulus encoding by the cerebellar cortex.
Deep brain stimulation (DBS) is effective in managing motor symptoms of Parkinson's disease in well-selected individuals. Recently, research has shown that DBS in the basal ganglia (BG) can alter neural circuits beyond the traditional basal ganglia-thalamus-cortical (BG-TH-CX) loop. For instance, functional imaging showed alterations in cerebellar activity with DBS in the subthalamic nucleus (STN). However, these imaging studies revealed very little about how cell-specific cerebellar activity responds to STN stimulation or if these changes contribute to its efficacy. In this study, we assess whether STN-DBS provides efficacy in managing motor symptoms in Parkinson's disease by recruiting cerebellar activity. We do this by applying STN-DBS in hemiparkinsonian rats and simultaneously recording neuronal activity from the STN, brainstem and cerebellum. We found that STN neurons decreased spiking activity by 55 % during DBS (P = 0.038), which coincided with a decrease in most pedunculopontine tegmental nucleus and Purkinje neurons by 29 % (P < 0.001) and 28 % (P = 0.003), respectively. In contrast, spike activity in the deep cerebellar nuclei increased 45 % during DBS (P < 0.001), which was likely from reduced afferent activity of Purkinje cells. Then, we applied STN-DBS at sub-therapeutic current along with stimulation of the deep cerebellar nuclei and found similar improvement in forelimb akinesia as with therapeutic STN-DBS alone. This suggests that STN-DBS can engage cerebellar activity to improve parkinsonian motor symptoms. Our study is the first to describe how STN-DBS in Parkinson's disease alters cerebellar activity using electrophysiology in vivo and reveal a potential for stimulating the cerebellum to potentiate deep brain stimulation of the subthalamic nucleus.
