Imaging dopamine's role in timing-based corticostriatal synaptic plasticity
Final Report Abstract
The corticostriatal pathway consists of neurons from all over the cortex that are targeting the principal neurons of the striatum, the spiny projection neurons (SPNs). Long-term changes in synaptic strength of the corticostriatal pathway are involved in motor learning and habit formation. The neuromodulator dopamine is thought to be also involved in these two learning processes, as well as it is involved in disease states like Parkinson's disease. However, how dopamine exactly acts at the synaptic level in the striatum and how it is contributing to corticostriatal plasticity is poorly understood. So far, in vivo and in vitro studies investigating dopamine's action during corticostriatal synaptic plasticity have relied on stimulation protocols using high frequency presynaptic stimulation. However, high frequency action potential firing of the presynaptic cortical neurons as well as of their postsynaptic striatal target neurons is not readily observed in vivo. In this study, we have applied stimulation protocols designed to activate the presynaptic cortical and the postsynaptic striatal neurons in a more sparse and low frequent manner. Specifically, presynaptic activation was evoked by electrical stimulation of cortical afferents to SPNs, resulting in EPSPs (excitatory postsynaptic potentials), recorded in SPNs via a patch-clamp electrode. Postsynaptic activation was provided by inducing action potentials (APs) in SPNs by somatic current injection via the patch-clamp electrode. Presynaptic and postsynaptic activation was paired with delay times on the order of tens of milliseconds, and repeatedly applied at a very low frequency of 0.1 Hz. We show that SPNs undergo long-term potentiation (LTP) when the presynaptically evoked EPSP was followed by an AP within 10 ms. With the reverse order of presynaptic and postsynaptic activation, specifically when an AP was followed by an EPSP within 30 ms to up to 150 ms, long-term depression (LTD) resulted. Thus, relatively sparse presynaptic and postsynaptic activation can result in bidirectional corticostriatal plasticity, depending on the exact timing and order of presynaptic and postsynaptic activity. We also show that dopamine receptor activation is required for this corticostriatal "spike-timing-dependent plasticity" (STOP). Different dopamine receptor subtypes seem to subserve different roles, since dopamine Di/D5 receptor activation is critically required for corticostriatal spike-timing-dependent LTP and LTD, whereas dopamine 02 receptor activation modulates the initial phase of plasticity without having an effect on the final amount of LTP and LTD. Together, these results show that the timing of postsynaptic action potentials to presynaptic cortical inputs is not enough to induce corticostriatal plasticity, but that an additional "reward" signal such as the activation of dopamine receptors is required.
Publications
- (2008) Dopamine receptor activation is required for corticostriatal spike-timing-dependent plasticity. J Neurosci 28: 2435-2446
Pawlak V, Kerr JN
