Dopamine Autoreceptor Regulation of a Hypothalamic Dopaminergic Network

Abstract

SummaryHow 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.

Oscillating from Neurosecretion to Multitasking Dopamine Neurons

“…Moreover, gonadotropin-releasing hormone neurons were found to lack classical axons, with the signal transmission function controlling release of this hormone in the median eminence being subsumed into an integrated dendrite and axon, termed a dendron (Herde et al, 2013). Stagkourakis et al (2016) now provide convincing evidence for autoregulatory control mechanisms in TIDA neurons that further the perception that these dopamine neurons are also more complex than original descriptions suggest. Such autoregulation would not be required for a simple neuroendocrine function involving secretion to regulate the pituitary gland.…”

“…Instead, they were thought to be controlled by a short feedback loop based on pituitary prolactin secretion (Advis et al, 1977) (Figure 1A). The data presented by Stagkourakis et al (2016) demonstrate that this perception was not completely accurate, and, in doing so, they open up significant new insights into the regulation and potential function of this physiologically relevant and intriguing dopamine population.…”

“… In this issue of Cell Reports , Stagkourakis et al (2016) report that oscillating hypothalamic TIDA neurons, previously thought to be simple neurosecretory neurons controlling pituitary prolactin secretion, control dopamine output via autoregulatory mechanisms and thus could potentially regulate other physiologically important hypothalamic neuronal circuits. …”

“…In particular, it is important to understand both the similarities and differences between different dopaminergic projections in order to fully appreciate the impact of pharmacological manipulation of dopamine systems in the treatment of these disorders. In this issue of Cell Reports , Stagkourakis et al (2016) provide novel insight into a specific dopamine population, the tuberoinfundibular dopamine (TIDA) neurons of the hypothalamus.…”

An updated view of hypothalamic–vascular–pituitary unit function and plasticity

“…One possible mechanism is the coordinated changes in firing rates of a subset of tuberoinfundibular dopamine neurons over tens of minutes; these correlate with episodic dopamine secretion recorded from multiple terminals at the median eminence in mice 2 . Gap junctions and local dendritic dopamine release have been proposed to mediate this activity 82,83 , and integration of single cell firing rates seems to be involved in the generation of longer dopamine release output events (N.…”