Long-term plasticity of glutamatergic input from the subthalamic nucleus to the entopeduncular nucleus

Eur J Neurosci. 2018 Sep;48(5):2139-2151. doi: 10.1111/ejn.14105. Epub 2018 Aug 31.


The hyperdirect pathway of the basal ganglia bypasses the striatum, and delivers cortical information directly to the subthalamic nucleus (STN). In rodents, the STN excites the two output nuclei of the basal ganglia, the entopeduncular nucleus (EP) and the substantia nigra reticulata (SNr). Thus, during hyperdirect pathway activation, the STN drives EP firing inhibiting the thalamus. We hypothesized that STN activity could induce long-term changes to the STN->EP synapse. To test this hypothesis, we recorded in the whole-cell mode from neurons in the EP in acute brain slices from rats while electrically stimulating the STN. Repetitive pre-synaptic stimulation generated modest long-term depression (LTD) in the STN->EP synapse. However, pairing EP firing with STN stimulation generated robust LTD that manifested for pre-before post-as well as for post- before pre-synaptic pairing. This LTD was highly sensitive to the time difference and was not detected at a time delay of 10 ms. To investigate whether post-synaptic calcium levels were important for LTD induction, we made dendritic recordings from EP neurons that revealed action potential back-propagation and dendritic calcium transients. Buffering the dendritic calcium concentration in the EP neurons with EGTA generated long term potentiation instead of LTD. Finally, mild LTD could be induced by post-synaptic activity alone that was blocked by an endocannabinoid 1 (CB1) receptor blocker. These results thus suggest there may be an adaptive mechanism for buffering the impact of the hyperdirect pathway on basal ganglia output which could contribute to the de-correlation of STN and EP firing.

Keywords: basal ganglia; entopeduncular nucleus; glutamate receptors; long-term plasticity; subthalamic nucleus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology*
  • Animals
  • Basal Ganglia / physiology
  • Corpus Striatum / physiology
  • Entopeduncular Nucleus / physiology*
  • Neural Pathways / physiology
  • Neuronal Plasticity / physiology*
  • Neurons / physiology
  • Rats, Wistar
  • Substantia Nigra / physiology
  • Subthalamic Nucleus / physiology*
  • Synapses / physiology
  • Time Factors