Network-wide modulation of synaptic plasticity and spike patterns in motor circuits after pallidal deep brain stimulation in a dystonia model.

Aims: We aimed to investigate the functional network effects of long-term deep brain stimulation (DBS) of the globus pallidus pars interna (GPi) on synaptic activity in motor thalamic and motor cortical neurons in an animal model of generalised dystonia (dt hamster) with a focus on understanding the underlying mechanisms of GPi-DBS in modulating neural activity.

Methods: Whole-cell recordings were performed on motor thalamic and motor cortical neurons from DBS-treated and sham-treated dt hamsters. Spontaneous synaptic activity was pharmacologically characterised and analysed by examining interspike intervals (ISI), postsynaptic current (PSC) frequencies, and discharge rates of spontaneous and evoked action potentials. Oscillatory patterns were also assessed to evaluate potential alterations in cortico-thalamo-cortical loops.

Results: The results revealed significant alterations in synaptic activity following long-term GPi-DBS. DBS-treated animals exhibited reduced ISI and increased PSC frequencies compared to sham-treated animals, with increased excitatory input to thalamic and a more clustered (though not more frequent) excitatory input to cortical M1. Fast oscillations were observed in both thalamic and motor cortical neurons, suggesting modulation of cortico-thalamo-cortical loops. While overall discharge rates of spontaneous and evoked action potentials remained unchanged, alterations in synaptic plasticity were noted, including increased PSC amplitudes and changes in inhibitory synaptic currents.

Conclusion And Main Finding: GPi-DBS modulates synaptic plasticity within the motor network by disrupting desynchronised neural activity. The alterations in pre- and postsynaptic mechanisms, including changes in inhibitory synaptic currents and axonal activity, lead to reorganising neuronal firing patterns and synaptic connectivity. These network-wide modulations may underpin the therapeutic effects of GPi-DBS in generalised dystonia.