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bioRxiv · 10.1101/2023.04.14.536959

Modeling synaptic integration of bursty and beta oscillatory inputs in ventromedial motor thalamic neurons in normal and parkinsonian states

Cavarretta, F.·Jaeger, D.
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Abstract

The Ventromedial Motor Thalamus (VM) is implicated in multiple motor functions and occupies a central position in the cortico-basal ganglia-thalamocortical loop. It integrates glutamatergic inputs from motor cortex (MC) and motor-related subcortical areas, and it is a major recipient of inhibition from basal ganglia. Previous experiments in vitro showed that dopamine depletion enhances the excitability of thalamocortical cells (TC) in VM due to reduced M-type potassium currents. To understand how these excitability changes impact synaptic integration in vivo, we constructed biophysically detailed VM TC models fit to normal and dopamine-depleted conditions, using the NEURON simulator. These models allowed us to assess the influence of excitability changes with dopamine depletion on the integration of synaptic inputs expected in vivo. We found that VM TCs in the dopamine-depleted state showed increased firing rates with the same synaptic inputs. Synchronous bursting in inhibitory input from the substantia nigra pars reticulata (SNR), as observed in parkinsonian conditions, evoked a post-inhibitory firing rate increase with a longer duration in dopamine-depleted than control conditions, due to different M-type potassium channel densities. With beta oscillations in the inhibitory inputs from SNR and the excitatory inputs from drivers and modulators, we observed spike-phase locking in the activity of the models in normal and dopamine-depleted states, which relayed and amplified the oscillations of the inputs, suggesting that the increased beta oscillations observed in VM of parkinsonian animals are predominantly a consequence of changes in the presynaptic activity rather than changes in intrinsic properties. Significance StatementThe Ventromedial Motor Thalamus is implicated in multiple motor functions. Experiments in vitro showed this area undergoes homeostatic changes following dopamine depletion (parkinsonian state). Here we studied the impact of these changes in vivo, using biophysically detailed modeling. We found that dopamine depletion increased firing rate in the ventromedial thalamocortical neurons and changed their responses to synchronous inhibitory inputs from substantia nigra reticulata. All thalamocortical neuron models relayed and amplified beta oscillations from substantia nigra reticulata and cortical/subcortical inputs, suggesting that increased beta oscillations observed in parkinsonian animals predominantly reflect changes in presynaptic activity.

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Cavarretta, F., Jaeger, D.. 2023-04-15. Modeling synaptic integration of bursty and beta oscillatory inputs in ventromedial motor thalamic neurons in normal and parkinsonian states. https://doi.org/10.1101/2023.04.14.536959

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