Fig. 12.

Corticostriatal synapse alterations in 6 months old Thy1-aSyn mice, prior to dopamine loss. Terminals from nigral dopaminergic neurons and from cortical glutamatergic neurons project to the striatum and form synapses onto GABAergic medium spiny neurons. Increased extrasynaptic dopamine results in alteration of dopaminergic modulation of the corticostriatal synapse. Reduced spontaneous and evoked excitatory postsynaptic currents (EPSCs) indicate decrease in neurotransmitter release at the corticostriatal synapse. Increased microglia activation and tumor necrosis factor-α (TNF-alpha) release might contribute to neuronal dysfunction in the striatum. AMPAR = xxxx; D1/2R = xxxx; D2R = xxxx; DAT = xxxx; NMDAR = xxxx; VMAT = xxxx.