Dichotomous Dopaminergic Control of Striatal Synaptic Plasticity

TLDR

Cortical inputs to striatal medium spiny neurons rely on D1 and D2 dopamine receptors to induce long‑term potentiation and depression, implying that plasticity should be unidirectional within each MSN subtype. Our experiments in dopamine‑receptor transgenic mice reveal that dopamine actually supports bidirectional, Hebbian plasticity in both MSN types, and that Parkinson’s disease models disrupt this balance, producing unidirectional changes that may contribute to network dysfunction.

Abstract

At synapses between cortical pyramidal neurons and principal striatal medium spiny neurons (MSNs), postsynaptic D1 and D2 dopamine (DA) receptors are postulated to be necessary for the induction of long-term potentiation and depression, respectively—forms of plasticity thought to underlie associative learning. Because these receptors are restricted to two distinct MSN populations, this postulate demands that synaptic plasticity be unidirectional in each cell type. Using brain slices from DA receptor transgenic mice, we show that this is not the case. Rather, DA plays complementary roles in these two types of MSN to ensure that synaptic plasticity is bidirectional and Hebbian. In models of Parkinson's disease, this system is thrown out of balance, leading to unidirectional changes in plasticity that could underlie network pathology and symptoms.