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

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

NATURVETENSKAP  -- Data- och informationsvetenskap -- Bioinformatik (hsv//swe)

NATURAL SCIENCES  -- Computer and Information Sciences -- Bioinformatics (hsv//eng)

Nyckelord

substantia nigra pars reticulata

short-term plasticity

basal ganglia

network model

subthalamic nucleus

globus pallidus

facilitation

depression

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)