Induction of striatal long‐term synaptic depression by moderate frequency activation of cortical afferents in rat

Abstract

The striatum regulates motor output, and it is thought that changes in the synaptic efficacy of inputs to the striatum contribute to motor learning and habit formation. Previously, several laboratories have observed that brief high frequency stimulation (HFS) of cortical afferents innervating the dorsolateral striatum induces a long-term decrease in synaptic efficacy called long-term depression (LTD). We recently showed that HFS-induced striatal LTD requires retrograde signalling involving postsynaptic release of endocannabinoids and activation of presynaptic CB1 cannabinoid receptors. In the present study we have employed whole-cell recording in brain slices to examine a new form of LTD at corticostriatal synapses that can be induced by a 10 Hz, 5 min train. The decrease in synaptic efficacy is associated with a decrease in presynaptic release probability, as demonstrated by a decrease in frequency but not amplitude of spontaneous excitatory postsynaptic currents (sEPSCs) and an increase in the paired pulse ratio (PPR). This form of LTD is blocked by antagonists for CB1 and D2 dopamine receptors and impaired by blockers of L-type calcium channels. However, 10 Hz-induced LTD does not depend on postsynaptic depolarization, unlike HFS-induced LTD. Furthermore, this new form of LTD is not prevented by treatments known to block HFS-induced LTD, including antagonism of metabotropic glutamate receptors (mGluRs), chelation of postsynaptic calcium, or intracellular application of an anandamide membrane transport inhibitor (VDM11). From these findings it is not clear that the endocannabinoid responsible for this form of LTD acts in a retrograde fashion, and the cellular source of endocannabinoid necessary for 10 Hz-induced LTD is as yet unknown. Our results demonstrate that a prolonged moderate frequency train induces cannabinoid-dependent LTD, further supporting the idea that endocannabinoids play a prominent role in the regulation of long-lasting changes in striatal output.