Striatal cholinergic receptor activation causes a rapid, selective, & state-dependent rise in corticostriatalβactivity

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 -HFO phase-amplitude coupling. Finally, the direction of β PDC distinguished between β subbands. This suggests: (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; (3) altered striatal cholinergic tone differentially modulates distinct β subbands.

A biophysical model of striatal microcircuits suggests gamma and beta oscillations interleaved at delta/theta frequencies mediate periodicity in motor control

“…Our model provides mechanistic explanations for all four oscillatory bands observed in ventral striatum in vivo (δ/θ, β, low γ, and high γ) [70]. Previous modeling and experiments suggest β can be generated by striatal SPNs [45,71,72]. Our results suggest that FSIs generate striatal γ, and that motor-and reward-related increases in γ power reflect increased striatal FSI activity.…”

“…In Parkinson's disease, which is characterized by motor deficits and chronic DA depletion, β power is correlated with the severity of bradykinesia [2]. Parkinsonian β may be generated by striatal D2 SPNs [45,71,72]. Parkinsonian conditions also produce high cholinergic tone [107], known to decrease the conductance of GABAergic FSI-SPN synapses [108].…”

“…The current study focuses on the oscillatory bands frequently observed in striatal local field potential: δ (1-3 Hz), θ (4-7 Hz), β (8-30 Hz), low γ (50)(51)(52)(53)(54)(55)(56)(57)(58)(59)(60), and high γ (70)(71)(72)(73)(74)(75)(76)(77)(78)(79)(80) [10,16,28]. Power in these bands consistently correlates with responses to task parameters including motor initiation, decision making, and reward [10][11][12]20].…”