Signal enhancement in the output stage of the basal ganglia by synaptic short-term plasticity in the direct, indirect, and hyperdirect pathways.

Mikael Lindahl,Iman Kamali Sarvestani,Orjan Ekeberg,Jeanette Hellgren Kotaleski

doi:10.3389/fncom.2013.00076

Mikael Lindahl, Iman Kamali Sarvestani + Show 2 more

Open Access

https://doi.org/10.3389/fncom.2013.00076

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Abstract

Many of the synapses in the basal ganglia display short-term plasticity. Still, computational models have not yet been used to investigate how this affects signaling. Here we use a model of the basal ganglia network, constrained by available data, to quantitatively investigate how synaptic short-term plasticity affects the substantia nigra reticulata (SNr), the basal ganglia output nucleus. We find that SNr becomes particularly responsive to the characteristic burst-like activity seen in both direct and indirect pathway striatal medium spiny neurons (MSN). As expected by the standard model, direct pathway MSNs are responsible for decreasing the activity in SNr. In particular, our simulations indicate that bursting in only a few percent of the direct pathway MSNs is sufficient for completely inhibiting SNr neuron activity. The standard model also suggests that SNr activity in the indirect pathway is controlled by MSNs disinhibiting the subthalamic nucleus (STN) via the globus pallidus externa (GPe). Our model rather indicates that SNr activity is controlled by the direct GPe-SNr projections. This is partly because GPe strongly inhibits SNr but also due to depressing STN-SNr synapses. Furthermore, depressing GPe-SNr synapses allow the system to become sensitive to irregularly firing GPe subpopulations, as seen in dopamine depleted conditions, even when the GPe mean firing rate does not change. Similar to the direct pathway, simulations indicate that only a few percent of bursting indirect pathway MSNs can significantly increase the activity in SNr. Finally, the model predicts depressing STN-SNr synapses, since such an assumption explains experiments showing that a brief transient activation of the hyperdirect pathway generates a tri-phasic response in SNr, while a sustained STN activation has minor effects. This can be explained if STN-SNr synapses are depressing such that their effects are counteracted by the (known) depressing GPe-SNr inputs.

Highlights

An important question in neuroscience is to understand how synaptic signaling contributes to network function in the brain
CHARACTERISTICS OF THE DERIVED MODEL NEURONS AND THEIR SYNAPTIC INPUTS The substantia nigra reticulata (SNr), globus pallidus externa (GPe) and subthalamic nucleus (STN) neuron models were tuned to exhibit properties that are characteristic of the firing of these neurons in vitro, exhibiting realistic membrane resistances (Figure 1A) and current frequency relationships (Figure 1B)
We have investigated how dynamical synapses in the direct, indirect and hyperdirect pathways quantitatively shape the activity in SNr neurons over time

Summary

Introduction

An important question in neuroscience is to understand how synaptic signaling contributes to network function in the brain. The effect of the synaptic signal varies with previous activity pattern either at one or at both sides of the synapse, and these modifications include short-term- to long-term plasticities, which together span from milliseconds up to months (Abbott and Regehr, 2004). The ability of synapses to perform non-linear transformations of signals over time makes them crucial components enabling a diverse set of circuit functions in the nervous system such as gain control, information filtering, coincident detection, short term- and long term memory (Abbott and Regehr, 2004; Deng and Klyachko, 2011). Synaptic short-term plasticity is prominent in the basal ganglia, it has not been included in computational models of the basal ganglia

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