Dopamine (DA) regulates synaptic plasticity in striatal medium spiny neurons (MSNs), with D1 and D2 receptors playing distinct roles. D1 receptors promote long-term potentiation (LTP), while D2 receptors promote long-term depression (LTD). However, previous studies suggested that DA was essential for both forms of plasticity. This study challenges that view, showing that D1 and D2 receptors in different MSN populations work together to enable bidirectional, Hebbian plasticity. In Parkinson's disease models, DA depletion disrupts this balance, leading to unidirectional plasticity and network dysfunction. The study used transgenic mice expressing green fluorescent protein (GFP) to identify D1 and D2 receptor-expressing MSNs. By pairing presynaptic stimulation with postsynaptic spikes, the researchers induced STDP, a form of spike-timing dependent plasticity. In D2 MSNs, this protocol induced LTP when presynaptic activity preceded postsynaptic spiking, and LTD when the order was reversed. In D1 MSNs, the protocol induced LTP when presynaptic activity followed postsynaptic spiking. These results suggest that D1 and D2 receptors in different MSN populations work together to enable bidirectional plasticity. The study also found that DA receptor signaling is necessary for the induction of both LTP and LTD. In D2 MSNs, blocking D2 receptors disrupted LTD, while blocking A2a receptors disrupted LTP. In D1 MSNs, blocking D1 receptors disrupted LTP, while blocking CB1 receptors disrupted LTD. These findings suggest that DA receptor signaling is essential for the induction of both forms of plasticity. The study also found that DA depletion in Parkinson's disease models led to unidirectional plasticity, suggesting that DA is necessary for maintaining bidirectional plasticity. The results suggest that DA neurons regulate striatal plasticity by modulating the activity of D1 and D2 receptors. This regulation is essential for maintaining the balance between LTP and LTD, which is necessary for normal striatal function. The study also suggests that DA depletion in Parkinson's disease leads to the loss of bidirectional plasticity, which may contribute to the symptoms of the disease.Dopamine (DA) regulates synaptic plasticity in striatal medium spiny neurons (MSNs), with D1 and D2 receptors playing distinct roles. D1 receptors promote long-term potentiation (LTP), while D2 receptors promote long-term depression (LTD). However, previous studies suggested that DA was essential for both forms of plasticity. This study challenges that view, showing that D1 and D2 receptors in different MSN populations work together to enable bidirectional, Hebbian plasticity. In Parkinson's disease models, DA depletion disrupts this balance, leading to unidirectional plasticity and network dysfunction. The study used transgenic mice expressing green fluorescent protein (GFP) to identify D1 and D2 receptor-expressing MSNs. By pairing presynaptic stimulation with postsynaptic spikes, the researchers induced STDP, a form of spike-timing dependent plasticity. In D2 MSNs, this protocol induced LTP when presynaptic activity preceded postsynaptic spiking, and LTD when the order was reversed. In D1 MSNs, the protocol induced LTP when presynaptic activity followed postsynaptic spiking. These results suggest that D1 and D2 receptors in different MSN populations work together to enable bidirectional plasticity. The study also found that DA receptor signaling is necessary for the induction of both LTP and LTD. In D2 MSNs, blocking D2 receptors disrupted LTD, while blocking A2a receptors disrupted LTP. In D1 MSNs, blocking D1 receptors disrupted LTP, while blocking CB1 receptors disrupted LTD. These findings suggest that DA receptor signaling is essential for the induction of both forms of plasticity. The study also found that DA depletion in Parkinson's disease models led to unidirectional plasticity, suggesting that DA is necessary for maintaining bidirectional plasticity. The results suggest that DA neurons regulate striatal plasticity by modulating the activity of D1 and D2 receptors. This regulation is essential for maintaining the balance between LTP and LTD, which is necessary for normal striatal function. The study also suggests that DA depletion in Parkinson's disease leads to the loss of bidirectional plasticity, which may contribute to the symptoms of the disease.