High frequency stimulation induces LTD of AMPA receptor-mediated postsynaptic responses and LTP of synaptically-evoked firing in the dorsolateral striatum

In the striatum, long term potentiation (LTP) and long-term depression (LTD) of glutamatergic transmission are believed to underlie motor learning and are impaired in animal models of Parkinson's disease. High frequency stimulation (HFS) is often used to induce synaptic plasticity in the brain. In the striatum, the polarity of HFS-induced plasticity is influenced by the recording conditions, which can differ between various studies. Here, we examined the ability of HFS to induce synaptic plasticity in the dorsolateral striatum in the presence of extracellular Mg2+ ions, with no GABAA receptor blocker, and without membrane depolarization during HFS. We found that HFS induced a LTD of excitatory postsynaptic currents (EPSCs) mediated by AMPA receptors (AMPARs) in medium spiny neurons (MSNs) recorded with whole-cell voltage-clamp. However, HFS induced a LTP of field excitatory postsynaptic potentials/population spikes (fEPSP/PSs), which was dependent on the stimulation intensity applied. The rate of synaptically-evoked spiking in MSNs, measured with cell-attached recordings, showed LTP following HFS. LTD and LTP were impaired in the dopamine-depleted striatum of 6-hydroxydopamine (6-OHDA) lesioned mice, a model of Parkinson's disease. This study shows that HFS induces opposing forms of dopamine-dependent synaptic plasticity in the striatum, i.e. LTD of AMPAR-EPSCs and LTP of both fEPSP/PS and synaptically-evoked firing in MSNs.