Dopamine Autoreceptor Regulation of a Hypothalamic Dopaminergic Network

Summary

How autoreceptors contribute to maintaining a stable output of rhythmically active neuronal circuits is poorly understood. Here, we examine this issue in a dopamine population, spontaneously oscillating hypothalamic rat (TIDA) neurons, that underlie neuroendocrine control of reproduction and neuroleptic side effects. Activation of dopamine receptors of the type 2 family (D2Rs) at the cell-body level slowed TIDA oscillations through two mechanisms. First, they prolonged the depolarizing phase through a combination of presynaptic increases in inhibition and postsynaptic hyperpolarization. Second, they extended the discharge phase through presynaptic attenuation of calcium currents and decreased synaptic inhibition. Dopamine reuptake blockade similarly reconfigured the oscillation, indicating that ambient somatodendritic transmitter concentration determines electrical behavior. In the absence of D2R feedback, however, discharge was abolished by depolarization block. These results indicate the existence of an ultra-short feedback loop whereby neuroendocrine dopamine neurons tune network behavior to echoes of their own activity, reflected in ambient somatodendritic dopamine, and also suggest a mechanism for antipsychotic side effects.

Graphical Abstract

Highlights

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  Frequency tuning by autoreceptors occurs in an oscillating dopamine neuron network

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  Dopamine reuptake and D2 receptors at the cell-body level determine frequency

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  Oscillation is controlled through the combination of pre- and postsynaptic actions

Abstract

Stagkourakis et al. describe an ultra-short feedback loop in hypothalamic rat dopamine (TIDA) neurons. Using electrophysiology, they show that TIDA network oscillations are tuned to ambient levels of dopamine. This homeostatic regulation, involving complementary sets of pre- and postsynaptic mechanisms, may contribute to the hormonal side effects of antipsychotics.