Input- and cell-type-specific endocannabinoid-dependent LTD in the striatum

Cell Rep. 2015 Jan 6;10(1):75-87. doi: 10.1016/j.celrep.2014.12.005. Epub 2014 Dec 24.


Changes in basal ganglia plasticity at the corticostriatal and thalamostriatal levels are required for motor learning. Endocannabinoid-dependent long-term depression (eCB-LTD) is known to be a dominant form of synaptic plasticity expressed at these glutamatergic inputs; however, whether eCB-LTD can be induced at all inputs on all striatal neurons is still debatable. Using region-specific Cre mouse lines combined with optogenetic techniques, we directly investigated and distinguished between corticostriatal and thalamostriatal projections. We found that eCB-LTD was successfully induced at corticostriatal synapses, independent of postsynaptic striatal spiny projection neuron (SPN) subtype. Conversely, eCB-LTD was only nominally present at thalamostriatal synapses. This dichotomy was attributable to the minimal expression of cannabinoid type 1 (CB1) receptors on thalamostriatal terminals. Furthermore, coactivation of dopamine receptors on SPNs during LTD induction re-established SPN-subtype-dependent eCB-LTD. Altogether, our findings lay the groundwork for understanding corticostriatal and thalamostriatal synaptic plasticity and for striatal eCB-LTD in motor learning.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basal Ganglia / metabolism
  • Basal Ganglia / pathology
  • Corpus Striatum / metabolism
  • Corpus Striatum / pathology
  • Endocannabinoids / metabolism*
  • Gene Expression
  • Learning / physiology
  • Long-Term Synaptic Depression*
  • Mice
  • Motor Neurons / metabolism
  • Motor Neurons / pathology
  • Neuronal Plasticity*
  • Receptor, Cannabinoid, CB1 / biosynthesis*
  • Receptor, Cannabinoid, CB1 / metabolism
  • Synapses / metabolism
  • Synapses / pathology
  • Thalamus / metabolism
  • Thalamus / pathology


  • Endocannabinoids
  • Receptor, Cannabinoid, CB1