Region-specific restoration of striatal synaptic plasticity by dopamine grafts in experimental parkinsonism

Intrastriatal transplantation of dopaminergic neurons can restore dopamine levels and improve parkinsonian deficits. However, underlying mechanisms are poorly understood. Here we evaluated the synaptic plasticity in the host striatum after neural transplantation using a rat model of Parkinson's disease. Naive rats showed distinct synaptic plasticity patterns in striatum. Ventrolateral striatum showed long-term potentiation (LTP) in approximately 63% of the neurons using the same protocol that elicited long-term depression (LTD) in the dorsolateral striatum. The LTP was linked to higher expression of post-synaptic AMPA- and GluN2B NMDA subunits and was shown not to be pathway dependent. In both regions, the synaptic plasticity was abolished after dopamine-depletion and could not be restored by grafted serotonergic neurons. Solely, dopamine grafts restored the LTP and partially restored motor deficits. The restoration was only present in ventrolateral striatum where grafted reinnervation was denser compared to the dorsolateral region. These data provide a first proof of concept that dopamine transplants are able to functionally integrate into the host brain and restore neuronal deficits in striatal synaptic plasticity after experimental PD. This might have implications for the limitation in symptomatic improvement following transplantation.