Striatal cholinergic receptor activation causes a rapid, selective and state‐dependent rise in cortico‐striatal β activity

Abstract

Cortico-basal ganglia-thalamic (CBT) β oscillations (15-30 Hz) are elevated in Parkinson's disease and correlated with movement disability. To date, no experimental paradigm outside of loss of dopamine has been able to specifically elevate β oscillations in the CBT loop. Here, we show that activation of striatal cholinergic receptors selectively increased β oscillations in mouse striatum and motor cortex. In individuals showing simultaneous β increases in both striatum and M1, β partial directed coherence (PDC) increased from striatum to M1 (but not in the reverse direction). In individuals that did not show simultaneous β increases, β PDC increased from M1 to striatum (but not in the reverse direction), and M1 was characterized by persistent β-high frequency oscillation phase-amplitude coupling. Finally, the direction of β PDC distinguished between β sub-bands. This suggests that (1) striatal cholinergic tone exerts state-dependent and frequency-selective control over CBT β power and coordination; (2) ongoing rhythmic dynamics can determine whether elevated β oscillations are expressed in striatum and M1; and (3) altered striatal cholinergic tone differentially modulates distinct β sub-bands.

Deep brain stimulation in the subthalamic nucleus for Parkinson’s disease can restore dynamics of striatal networks

“…Specifically, the beta oscillations will be exaggerated under conditions of high cholinergic tone or under conditions that tonically increase MSN excitation, such as loss of dopaminergic stimulation of D2 receptors. Consistent with our modeling findings, increasing the striatal cholinergic tone of normal mice produced robust, exaggerated beta oscillation in both the striatal local field potential and in cortex [13,84,85] as well as parkinsonian-like behavioral deficits [84]. Exaggerated beta oscillations further emerge in the striatal LFP of parkinsonian rats [86,87] and parkinsonian non-human primates [88,89].…”

D1/D5 Inverse Agonists Restore Striatal Cholinergic Interneuron Physiology in Dyskinetic Mice

“…Therefore, the SCIN hyperexcitability observed in l ‐dopa off‐states may further worsen the already established striatal hypercholinergic state, 4,75,76 aggravating the imbalance towards the indirect pathway that causes bradykinesia 77‐79 . Moreover, the mechanisms of the burst‐pause pattern likely change SCIN frequency tuning to synaptic inputs contributing to aberrant circuit oscillations 80‐83 . Consequently, higher l ‐dopa levels would be needed to escape from the off‐medication state, which further promotes the emergence of motor fluctuations 2,85 .…”

“…[77][78][79] Moreover, the mechanisms of the burst-pause pattern likely change SCIN frequency tuning to synaptic inputs contributing to aberrant circuit oscillations. [80][81][82][83] Consequently, higher L-dopa levels would be needed to escape from the off-medication state, which further promotes the emergence of motor fluctuations. 2,85 Here we show that reducing D5R ligand-independent activity with inverse agonists restores normal SCIN physiology, and we propose that targeting D5R ligand-independent activity in SCIN could have therapeutic effects for PD and LID by normalizing striatal cholinergic signaling.…”

Orchestration of brain oscillations: principles and functions

“…A review contributed by Singh focuses on the various observations of aberrant oscillatory activity within the cortico‐basal ganglia‐thalamic (CBT) observed in patients with Parkinson Disease (Singh, ), and an empirical study by Pittman‐Polletta et al . () describes the potential mechanism underlying these anomalies. Another neurodevelopmental condition oft‐linked with aberrant oscillatory functioning is autism (Murphy et al ., ), especially so in the gamma band (David et al ., ).…”