Heterosynaptic LTP of GABAergic inputs to dopaminergic neurons




Simmons, DeNard Vincent

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The net output of a dopamine neuron is partly regulated by its inhibitory inputs. Persistent increases in the synaptic weight of these inputs can significantly diminish synaptic release of dopamine. It has been demonstrated that GABAergic inputs onto dopamine neurons in the ventral tegmental area exhibit long term potentiation (LTP GABA) following high frequency activity at glutamatergic inputs onto the same cell. Through this heterosynaptic mechanism, high frequency activation of glutamatergic synapses increases the synaptic weight of neighboring GABAergic synapses. It is unknown however which GABAergic inputs participate in LTPGABA. Rostromedial Tegmental nucleus (RMTg) neurons, local ventral tegmental area (VTA) GABA neurons, and nucleus accumbens (NAc) projection neurons are prominent GABAergic projections to ventral tegmental area dopamine neurons, and contribute to reward processing. I infected each nucleus with an adeno-associated virus that promotes the expression of the light-activated protein, channelrhodopsin, at synaptic terminals upon dopamine neurons. These inputs were selectively stimulated with light. High frequency excitation of glutamate release upon VTA dopamine neurons induces LTP GABA upon NAc and VTA GABA specific inputs, but not inputs arising from the RMTg. LTPGABA also enhanced VTA GABA and NAc, but not RMTG specific inhibition of tonic action potential firing. An alternative potentiation induced by activation of the enzyme adenylyl cyclase successfully potentiated RMTg alongside NAc and VTA GABA inputs, suggesting different mechanisms of plasticity differ in their input specificity.


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Dopamine, GABA, LTP, VTA



Integrative Biology