Changes in neuronal activity of cortico‐basal ganglia–thalamic networks induced by acute dopaminergic manipulations in rats

Abstract

The basal ganglia are thought to be particularly sensitive to changes in dopaminergic tone, and the realization that reduced dopaminergic signaling causes pronounced motor dysfunction is the rationale behind dopamine replacement therapy in Parkinson's disease. It has, however, proven difficult to identify which neurophysiological changes that ultimately lead to motor dysfunctions. To clarify this, we have here recorded neuronal activity throughout the cortico-basal ganglia-thalamic circuits in freely behaving rats during periods of immobility following acute dopaminergic manipulations, involving both vesicular dopamine depletion and antagonism of D1 and D2 type dopamine receptors. Synchronized and rhythmic activities were detected in the form of betaband oscillations in local field potentials and as cortical entrainment of action potentials in several basal ganglia structures. Analyses of the temporal development of synchronized oscillations revealed a spread from cortex to gradually also include deeper structures. In addition, firing rate changes involving neurons in all parts of the network were observed. These changes were typically relatively balanced within each structure, resulting in negligible net rate changes. Animals treated with D1 receptor antagonist showed a rapid onset of hypokinesia that preceded most of the neurophysiological changes, with the exception of these balanced rate changes. Parallel rate changes in functionally coupled ensembles of neurons in different structures may therefore be the first step in a cascade of neurophysiological changes underlying motor symptoms in the parkinsonian state. We suggest that balanced rate changes in distributed networks are possible mechanism of disease that should be further investigated in conditions involving dopaminergic dysfunction.

Modulation of dopamine tone induces frequency shifts in cortico-basal ganglia beta oscillations

“…However, the mechanisms that determine and regulate properties of beta oscillatory activity, like frequency, power and coherence, are still not well defined. There is a significant upregulation of the power (amplitude) of beta activity in the BG of patients with Parkinson’s disease (PD) 2 – 4 and PD animal models 5 – 7 . In line with the “status quo” hypothesis, PD beta activity has been correlated with akinetic symptoms 8 .…”

The Association of Dexmedetomidine with Firing Properties in Pallidal Neurons

“…27 Accordingly, dopaminergic manipulations through the inhibition of tyrosine hydroxylase and the use of D1/D2 receptor antagonists have been shown to alter neuronal firing patterns in the basal ganglia, including the GPi. 28 Alternatively, the effect of DEX on neuronal activity in the GPi could be explained by a direct activation of locally expressed alpha-2 receptors. Between the three subtypes of alpha-adrenergic receptors, the alpha-2c subtype has been found to be highly expressed in the basal ganglia.…”

Dopamine depletion can be predicted by the aperiodic component of subthalamic local field potentials

“…In fact, many studies in humans and animal models have reported pathological PD symptoms without significant beta oscillation. [19][20][21][22] We noted the possibility that the aperiodic (nonoscillatory) component, which is the component of power spectral densities (PSD) in local field potentials (LFP) that does not include the periodic (oscillatory) component, can be a biomarker reflecting behavioral and cognitive states. 23,24 The aperiodic component can be described by a Lorentzian function as 𝐿 = 𝑏 − log(𝑘 + 𝑓 −𝜒 ), where 𝑏 , 𝑘 , and 𝜒 represent the aperiodic offset, the knee parameter, and the aperiodic exponent (see Methods for details).…”

“…However, beta frequency oscillation is far from a robust biomarker of PD. In fact, many studies in humans and animal models have reported pathological PD symptoms without significant beta oscillation (Bronte-Stewart et al, 2009; Ivica et al, 2018; Pan et al, 2016; Rosa et al, 2011). We noted the possibility that the aperiodic (nonoscillatory) component, which is the component of power spectral densities (PSD) in local field potentials (LFP) that does not include the periodic (oscillatory) component, can be a biomarker reflecting behavioral and cognitive states (Belova et al, 2021; Donoghue et al, 2020).…”