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

Adam, Elie M.; Brown, Emery N.; McCarthy, Michelle M.

doi:10.1073/pnas.2120808119

Cited by 24 publications

(17 citation statements)

References 150 publications

(384 reference statements)

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“…Further limitations of our model include the lack of dynamics to account for plasticity effects, and the fact that selecting an adaptive integrate and fire neuron model we did not take into account specific currents that are included in Hodgkin and Huxley models of basal ganglia (e.g. [ 89 ]).…”

Section: Discussionmentioning

confidence: 99%

Dopamine depletion leads to pathological synchronization of distinct basal ganglia loops in the beta band

Ortone¹,

Vergani²,

Ahmadipour³

et al. 2023

PLoS Comput Biol

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Motor symptoms of Parkinson’s Disease (PD) are associated with dopamine deficits and pathological oscillation of basal ganglia (BG) neurons in the β range ([12-30] Hz). However, how dopamine depletion affects the oscillation dynamics of BG nuclei is still unclear. With a spiking neurons model, we here capture the features of BG nuclei interactions leading to oscillations in dopamine-depleted condition. We highlight that both the loop between subthalamic nucleus (STN) and Globus Pallidus pars externa (GPe) and the loop between striatal fast spiking and medium spiny neurons and GPe display resonances in the β range, and synchronize to a common β frequency through interaction. Crucially, the synchronization depends on dopamine depletion: the two loops are largely independent for high levels of dopamine, but progressively synchronize as dopamine is depleted due to the increased strength of the striatal loop. The model is validated against recent experimental reports on the role of cortical inputs, STN and GPe activity in the generation of β oscillations. Our results highlight the role of the interplay between the GPe-STN and the GPe-striatum loop in generating sustained β oscillations in PD subjects, and explain how this interplay depends on the level of dopamine. This paves the way to the design of therapies specifically addressing the onset of pathological β oscillations.

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Section: Discussionmentioning

confidence: 99%

Dopamine depletion leads to pathological synchronization of distinct basal ganglia loops in the beta band

Ortone¹,

Vergani²,

Ahmadipour³

et al. 2023

PLoS Comput Biol

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“…Because the recording site was >1.3 mm upstream of the stimulation site, the excitation induced at the efferent axons by the stimulation should have propagated antidromically along the axons to close to the INs in the recording site before activating the INs through axon branches (see the pathway denoted by the orange curve in Figure 1 a). The experiment provides a new method to investigate the antidromic activations of efferent fibers on the local INs rather than the orthodromic activations of afferent fibers, as in previous studies [ 14 , 15 , 16 ].…”

Section: Discussionmentioning

confidence: 99%

“…The action potential induced by a pulse on the axonal membrane can simultaneously propagate along the axon in two directions: orthodromic propagation to the axonal terminals and antidromic propagation to the neuronal soma [ 9 ]. Studies have shown that through orthodromic propagations, HFS at afferent axons can increase the firing of the postsynaptic neurons (including the interneurons of feedforward circuits) in the downstream area of the stimulation site via synaptic transmissions at axonal terminals [ 14 , 15 , 16 ]. However, it is not clear yet whether the HFS-induced excitation at efferent axons can activate the interneurons of local feedback circuits in the upstream area of the stimulation site through antidromic propagations (see Figure 1 a).…”

Section: Introductionmentioning

confidence: 99%

Activating Interneurons in Local Inhibitory Circuits by High-Frequency Stimulations at the Efferent Fibers of Pyramidal Neurons in Rat Hippocampal CA1 Region

Feng

Wang

et al. 2022

Brain Sciences

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Stimulation-induced inhibition is one of the important effects of high-frequency stimulation (HFS) utilized by the therapy of deep brain stimulation (DBS) to treat certain neurological diseases such as epilepsy. In order to explore the stimulation sites to induce inhibition, this study investigated the activation effect of HFS of efferent fibers on the local inhibitory interneurons (IN). Antidromic HFS (A-HFS) of 100 Hz pulses was applied for 2 min at the efferent fibers—the alveus (i.e., the axons of pyramidal neurons) in the hippocampal CA1 region of anesthetized rats. Single unit spikes of INs in local feedback inhibitory circuits, as well as antidromically-evoked population spikes (APS) of pyramidal neurons, were recorded simultaneously in the CA1 region upstream of the stimulation site. Results showed that during the late 60 s of A-HFS, with a substantial suppression in APS amplitudes, the mean firing rate of INs was still significantly greater than the baseline level even when the A-HFS was applied with a weak pulse intensity of 0.08 ± 0.05 mA (9 rats). With a strong pulse intensity of 0.33 ± 0.08 mA (10 rats), the mean firing rate of INs was able to keep at a high level till the end of A-HFS. In addition, the mean latency of IN firing was significantly prolonged during the sustained A-HFS, indicating that alterations had been generated in the pathway to activate INs by the stimulations at efferent fibers. The results suggested that HFS at efferent fibers with various stimulation intensities can modulate the firing of local inhibitory neurons. The finding provides new clues for selecting stimulation sites to enhance inhibition in neural circuits by DBS.

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“…The dynamics and structure of neuronal networks can be manipulated by stimulation 35 , 37 , 43 , 54 , 73 – 83 . We use an anti-kindling coordinated reset (CR) stimulation to desynchronize initially synchronized networks.…”

Section: Methodsmentioning

confidence: 99%

Dynamics of phase oscillator networks with synaptic weight and structural plasticity

Chauhan

Khaledi-Nasab

Neiman

et al. 2022

Sci Rep

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We study the dynamics of Kuramoto oscillator networks with two distinct adaptation processes, one varying the coupling strengths and the other altering the network structure. Such systems model certain networks of oscillatory neurons where the neuronal dynamics, synaptic weights, and network structure interact with and shape each other. We model synaptic weight adaptation with spike-timing-dependent plasticity (STDP) that runs on a longer time scale than neuronal spiking. Structural changes that include addition and elimination of contacts occur at yet a longer time scale than the weight adaptations. First, we study the steady-state dynamics of Kuramoto networks that are bistable and can settle in synchronized or desynchronized states. To compare the impact of adding structural plasticity, we contrast the network with only STDP to one with a combination of STDP and structural plasticity. We show that the inclusion of structural plasticity optimizes the synchronized state of a network by allowing for synchronization with fewer links than a network with STDP alone. With non-identical units in the network, the addition of structural plasticity leads to the emergence of correlations between the oscillators’ natural frequencies and node degrees. In the desynchronized regime, the structural plasticity decreases the number of contacts, leading to a sparse network. In this way, adding structural plasticity strengthens both synchronized and desynchronized states of a network. Second, we use desynchronizing coordinated reset stimulation and synchronizing periodic stimulation to induce desynchronized and synchronized states, respectively. Our findings indicate that a network with a combination of STDP and structural plasticity may require stronger and longer stimulation to switch between the states than a network with STDP only.

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

Cited by 24 publications

References 150 publications

Dopamine depletion leads to pathological synchronization of distinct basal ganglia loops in the beta band

Dopamine depletion leads to pathological synchronization of distinct basal ganglia loops in the beta band

Activating Interneurons in Local Inhibitory Circuits by High-Frequency Stimulations at the Efferent Fibers of Pyramidal Neurons in Rat Hippocampal CA1 Region

Dynamics of phase oscillator networks with synaptic weight and structural plasticity

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