Existence of long-lasting experience-dependent plasticity in endocrine cell networks

Abstract

Experience-dependent plasticity of cell and tissue function is critical for survival by allowing organisms to dynamically adjust physiological processes in response to changing or harsh environmental conditions. Despite the conferred evolutionary advantage, it remains unknown whether emergent experience-dependent properties are present in cell populations organized as networks within endocrine tissues involved in regulating body-wide homeostasis. Here we show, using lactation to repeatedly activate a specific endocrine cell network in situ in the mammalian pituitary, that templates of prior demand are permanently stored through stimulus-evoked alterations to the extent and strength of cell–cell connectivity. Strikingly, following repeat stimulation, evolved population behaviour leads to improved tissue output. As such, long-lasting experience-dependent plasticity is an important feature of endocrine cell networks and underlies functional adaptation of hormone release.

Plasticity of Hypothalamic Dopamine Neurons during Lactation Results in Dissociation of Electrical Activity and Release

“…To support this point, we show that D 2 antagonists increase plasma PRL levels in virgin animals by releasing the inhibitory tone on the pituitary (Mueller et al, 1976;Russell et al, 2000;Anderson et al, 2008;Hodson et al, 2012). During lactation, lactotrophs continue to express D 2 receptors (Pazos et al, 1985), and the pituitary remains sensitive to DA receptor agonists (Li et al, 1999).We show that treatment with D 2 antagonists did not generate a significant increase in PRL levels during lactation, confirming that the endogenous inhibitory DA tone is strongly reduced.…”

Lipotoxicity disrupts incretin-regulated human β cell connectivity

“…Since exocytosis in electrically excitable endocrine cells is Ca 2+ dependent (32), the effects of intervention on the cell population dynamics underlying insulin release were determined by subjecting the resulting traces to large-scale correlation analyses (31). We note that, although α and other neuroendocrine cells comprise a substantial proportion (~40%) of the human islet (26), the former are unlikely to contribute to the recordings here, since elevated glucose is expected to have no effect or to reduce intracellular free Ca 2+ concentrations ([Ca 2+ ] i ) in these cells (33).…”

“…Using in situ imaging approaches, together with large-scale correlation analyses to map cell-cell interconnectivity (31), we demonstrate that GLP-1 recruits a highly coordinated subnetwork of β cells to augment GSIS, and this is targeted by lipotoxic insults to reduce insulin secretion. Providing evidence for an association with circulating lipid levels in humans, donor BMI was found to be negatively correlated with the coordinated β cell responses to GLP-1.…”

The Molecular Cell Biology of Anterior Pituitary Cells

“…Likewise, the lactotroph network retains functional connectivity through changes in the extent and strength of cellÀcell communication, allowing repeated lactation demands to be met with evolved network dynamics and improved tissue output. 49 Thus, experience-dependent plasticity allows lactotrophs to adapt their hormone releasing activity upon repeated stimulation, a feature that is likely shared by other endocrine cells within the anterior pituitary and, possibly, throughout the body. Endocrine cells of the anterior pituitary have a remarkably varied signaling toolkit at their disposal which, in combination with GPCR expression profiles, and gap junctional electrical coupling, may allow incoming signals to be processed and propagated from cell to cell in a specific manner.…”

“…This concept has been recently illustrated in female mice that underwent one or more lactations to repeatedly and selectively stimulate activity of pituitary lactotrophs. 49 Throughout the lactotroph population, each lactation event induced alterations in functional connectivity through changes in structural connectivity mediated by differential homotypic lactotrophÀlactotroph gap junctional contacts. Following weaning, the lactotroph population is able to maintain the pattern of functional connectivity for weeks to months, a hallmark of long-term experiencedependent plasticity that is reminiscent to that observed in neurons.…”