RT Journal Article
SR Electronic
T1 Transient Response of Basal Ganglia Network in Healthy and Low-Dopamine State
JF eneuro
JO eNeuro
FD Society for Neuroscience
SP ENEURO.0376-21.2022
DO 10.1523/ENEURO.0376-21.2022
VO 9
IS 2
A1 Chakravarty, Kingshuk
A1 Roy, Sangheeta
A1 Sinha, Aniruddha
A1 Nambu, Atsushi
A1 Chiken, Satomi
A1 Hellgren Kotaleski, Jeanette
A1 Kumar, Arvind
YR 2022
UL http://www.eneuro.org/content/9/2/ENEURO.0376-21.2022.abstract
AB The basal ganglia (BG) are crucial for a variety of motor and cognitive functions. Changes induced by persistent low-dopamine (e.g., in Parkinson’s disease; PD) result in aberrant changes in steady-state population activity (β band oscillations) and the transient response of the BG. Typically, a brief cortical stimulation results in a triphasic response in the substantia nigra pars reticulata (SNr; an output of the BG). The properties of the triphasic responses are shaped by dopamine levels. While mechanisms underlying aberrant steady state activity are well studied, it is still unclear which BG interactions are crucial for the aberrant transient responses in the BG. Moreover, it is also unclear whether mechanisms underlying the aberrant changes in steady-state activity and transient response are the same. Here, we used numerical simulations of a network model of BG to identify the key factors that determine the shape of the transient responses. We show that an aberrant transient response of the SNr in the low-dopamine state involves changes in the direct pathway and the recurrent interactions within the globus pallidus externa (GPe) and between GPe and subthalamic nucleus (STN). However, the connections from D2-type spiny projection neurons (D2-SPN) to GPe are most crucial in shaping the transient response and by restoring them to their healthy level, we could restore the shape of transient response even in low-dopamine state. Finally, we show that the changes in BG that result in aberrant transient response are also sufficient to generate pathologic oscillatory activity in the steady state.