Dysregulation of external globus pallidus-subthalamic nucleus network dynamics in Parkinsonian mice

Ryan F. Kovaleski, Joshua W. Callahan, Marine Chazalon, Jérôme Baufreton, Mark D. Bevan
. 2019-09-20; :
DOI: 10.1101/774091

Reciprocally connected GABAergic external globus pallidus (GPe) and glutamatergic subthalamic nucleus (STN) neurons form a key, centrally-positioned network within the basal ganglia, a group of subcortical brain nuclei critical for voluntary movement. In Parkinson’s disease (PD) and its models, abnormal rates and patterns of GPe-STN network activity are linked to motor dysfunction. Using cell class-specific optogenetic identification and inhibition approaches during cortical slow-wave activity and activation, we report that in dopamine-depleted mice 1) D2 dopamine receptor expressing striatal projection neurons (D2-SPNs) are hyperactive 2) prototypic parvalbumin (PV)-expressing GPe neurons are excessively patterned by D2-SPNs 3) despite being disinhibited, STN neurons are not hyperactive 4) the STN opposes rather than facilitates abnormal striatopallidal patterning. Together with recent studies, these data argue that in Parkinsonian mice abnormal, temporally offset PV GPe neuron and STN activity results from increased striatopallidal transmission and that compensatory plasticity within the STN prevents its hyperactivity.

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