Frequency‐selectivity of a thalamocortical relay neuron during Parkinson’s disease and deep brain stimulation: a computational study

Abstract

In this computational study, we investigated (i) the functional importance of correlated basal ganglia (BG) activity associated with Parkinson's disease (PD) motor symptoms by analysing the effects of globus pallidus internum (GPi) bursting frequency and synchrony on a thalamocortical (TC) relay neuron, which received GABAergic projections from this nucleus; (ii) the effects of subthalamic nucleus (STN) deep brain stimulation (DBS) on the response of the TC relay neuron to synchronized GPi oscillations; and (iii) the functional basis of the inverse relationship that has been reported between DBS frequency and stimulus amplitude, required to alleviate PD motor symptoms [A. L. Benabid et al. (1991)Lancet, 337, 403-406]. The TC relay neuron selectively responded to and relayed synchronized GPi inputs bursting at a frequency located in the range 2-25 Hz. Input selectivity of the TC relay neuron is dictated by low-threshold calcium current dynamics and passive membrane properties of the neuron. STN-DBS prevented the TC relay neuron from relaying synchronized GPi oscillations to cortex. Our model indicates that DBS alters BG output and input selectivity of the TC relay neuron, providing an explanation for the clinically observed inverse relationship between DBS frequency and stimulus amplitude.

Do gap junctions regulate synchrony in the Parkinsonian basal ganglia?

“…In contrast, entrainment of thalamic cells by basal ganglia input seems to be common in birds . Computational models, however, have assumed that GPi output has prominent cell-to-cell effects on thalamus, at least under parkinsonian conditions and in particular after the occurrence of bursts in GPi [Rubin and Terman, 2004, Guo et al, 2008, Guo and Rubin, 2011, Reitsma et al, 2011, Cagnan et al, 2009, Pirini et al, 2009, Meijer et al, 2011, Cleary et al, 2013. Although we found high LFP correlations between GPi and VLa, it is not clear which physiological properties are actually reflected in these correlations, and whether they describe a transmission of information.…”

Neural network dynamics in Parkinson's disease

“…With optimized stimulation parameters, established empirically [146,177,219,220] and confirmed theoretically [38,53,137], STN-DBS is able to reduce dyskinesia and to improve motor symptoms including tremor, bradykinesia and rigidity [109,179]. However, STN-DBS is less effective for gait disturbance and postural instability, and its therapeutic benefit may decline over time [109,179].…”

Simulating Idiopathic Parkinson's Disease by In Vitro and Computational Models

“…In two recent studies we have investigated how DBS can affect the functioning of the thalamus as a relay station (Cagnan et al, 2009;Meijer et al, 2011). Although this is a simplication, it is presumed that this relay should retransmit incoming information from cortex and sensory systems back to cortex.…”

“…Additionally we investigated the frequency dependence of this therapeutic regime and showed that in the model it persists to frequencies as low as 60 Hz, although the plateau starts at 100 Hz. In Cagnan et al (2009) we considered a similar setup but considered the frequency content of the output. In particular, we showed that DBS can diminish the power at pathological frequencies in the spectrum of the thalamic output.…”

“…One of the aims of these computational models is to understand the mechanism of DBS. This review relies also on earlier publications, congress abstracts and presented posters (Cagnan et al, 2009;Heida et al, , 2010aLourens et al, 2009Lourens et al, , 2011Marani et al, 2008Marani et al, , 2010Meijer et al, in press;Moroney et al, 2008;Stegenga et al, 2009Stegenga et al, , 2010a.…”