Network oscillation rules imposed by species-specific electrical coupling

Abstract

Electrical junctions are widespread within the mammalian CNS. Yet, their role in organizing neuronal ensemble activity remains incompletely understood. Here, in a functionally well-characterized system – neuroendocrine tuberoinfundibular dopamine (TIDA) neurons - we demonstrate a striking species difference in network behavior: rat TIDA cells discharge in highly stereotyped, robust, synchronized slow oscillations, whereas mouse oscillations are faster, flexible and show substantial cell-to-cell variability. We show that these distinct operational modes are explained by the presence of strong TIDA-TIDA gap junction coupling in the rat, and its complete absence in the mouse. Both species, however, encompass a similar heterogeneous range of intrinsic resonance frequencies, suggesting similar network building blocks. We demonstrate that gap junctions select and impose the slow network rhythm. These data identify a role for electrical junctions in determining oscillation frequency and show how related species can rely on distinct network strategies to accomplish adaptive control of hormone release.

Adaptive resetting of tuberoinfundibular dopamine (TIDA) network activity during lactation in mice

“…This current is implicated in network rhythmicity (see (Luthi and McCormick, 1998), and contributes to depolarization of the resting membrane potential (Maccaferri et al, 1993); see (He et al, 2014), as observed in the lactating mothers (present results). Indeed, we have described a correlation between depolarization and oscillation frequency in mouse TIDA neurons, (Stagkourakis et al, 2018) and the present data show that pharmacological blockade of I h reduces the lactation-associated fast rhythm similar to the rate of nulliparous dams.…”

“…Individual cells were marked as regions of interest (ROIs) from the image sequences i.e, all positive cells in one plane. Consistent with previous studies in mice, both oscillating and nonoscillating DAT-GCaMP3 cells were found (Stagkourakis et al, 2018;Zhang and van den Pol, 2015). Our focus in this study was on the oscillating population, which was selected by the fold difference in the intensity signal (≥ 1%) and the rhythmicity index (defined below; ≥ 0.2).…”

“…The issue of adaptive control of TIDA neurons is interesting, not only for their role in reproduction and nursing, but also for the intriguing pattern of their discharge activity, organized as slow, regular membrane potential oscillations (Lyons et al, 2010). These oscillations can be observed by whole-cell patch clamp recording as well as Ca 2+ imaging in both rats and mice, albeit with species-specific features in network configuration (Stagkourakis et al, 2018). TIDA network activity can be modulated by several hormones and transmitters implicated in prolactin control (Briffaud et al, 2015;Lyons et al, 2016;Stagkourakis et al, 2016).…”

Dopamine Release Dynamics in the Tuberoinfundibular Dopamine System

“…The expression of DAT in TIDA neurons is well documented (Meister and Elde, 1993;Revay et al, 1996;Demaria et al, 2000;Stagkourakis et al, 2018), yet the functional role of the transporter within the lactotropic axis remains controversial (Demarest and Moore, 1979;Annunziato et al, 1980;Meister and Elde, 1993;Revay et al, 1996;Bossé et al, 1997;Demaria et al, 2000;Stagkourakis et al, 2018). To assess whether reuptake is involved at determining dopamine levels at the entry to the portal vasculature, we performed optogenetic stimulation of TIDA terminals in the ME, in the absence and presence of the clinically prescribed DAT blocker, methylphenidate (Taylor and Ho, 1978;Volkow et al, 1999a, b).…”

“…Dopamine, released in the median eminence (ME) for passage to the hypophyseal portal blood circulation, tonically inhibits the lactotropes through dopamine D2-type receptors (Gudelsky, 1981;Malgaroli et al, 1987;Israel et al, 1990;Lledo et al, 1990;Stefaneanu et al, 2000). Recent studies have revealed distinguishing electrophysiological characteristics of TIDA cells (Lyons et al, 2010), including the capacity for a variable repertoire of firing frequencies in mouse neurons (Romanò et al, 2013;Stagkourakis et al, 2018).…”