Induction frequency affects cortico-striatal synaptic plasticity with implications for frequency filtering

Long-term synaptic depression (LTD) in cortico-striatal circuits is initiated by depolarization of striatal medium spiny neurons through a convergent cortical glutamatergic input. This produces retrograde endocannabinoid signaling to presynaptic cortical terminals and eventually results in long term (>30 min) decreases in glutamate release. These same circuits can also undergo short-term depression (STD) through a less well-defined process in which the magnitude of postsynaptic responses returns to baseline levels within 10 min. Additionally, the cortico-striatal circuit shows characteristics of a GABAA receptor-dependent low-pass filter, which results in significant attenuation of high frequency cortical inputs. The majority of in vitro studies of LTD have used a 100-Hz induction paradigm and it is unclear whether other frequencies, which may also have physiological relevance, have equivalent ability to induce this form of plasticity. Here we have investigated the effectiveness of a range of induction paradigms in producing LTD in cortico-striatal circuits, and demonstrate that some lower frequency paradigms, with perhaps more physiological relevance, are more effective at inducing LTD. We also show that GABAA receptor-dependent frequency filtering in this circuit is altered following the induction of LTD and STD suggesting an important role for synaptic depression in signal processing in these circuits.