Uncoupling of EphA/ephrinA Signaling and Spontaneous Activity in Neural Circuit Wiring

Abstract

Classic studies have proposed that genetically encoded programs and spontaneous activity play complementary but independent roles in the development of neural circuits. Recent evidence, however, suggests that these two mechanisms could interact extensively, with spontaneous activity affecting the expression and function of guidance molecules at early developmental stages. Here, using the developing chick spinal cord and the mouse visual system to ectopically express the inwardly rectifying potassium channel Kir2.1 in individual embryonic neurons, we demonstrate that cell-intrinsic blockade of spontaneous activity in vivo does not affect neuronal identity specification, axon pathfinding, or EphA/ephrinA signaling during the development of topographic maps. However, intrinsic spontaneous activity is critical for axon branching and pruning once axonal growth cones reach their correct topographic position in the target tissues. Our experiments argue for the dissociation of spontaneous activity from hard-wired developmental programs in early phases of neural circuit formation.

A long Stokes shift red fluorescent Ca2+ indicator protein for two-photon and ratiometric imaging

“…Of these new colours, red fluorescent indicators have the greatest potential to challenge the latest generation of highly optimized GCaMP variants 7 as the preferred tools for in vivo imaging. The versatility of currently available red FP-based Ca 2+ indicators has been demonstrated in various tissues and organisms including the retinotectal system in zebrafish 13 , mushroom body neurons in Drosophila 14,15 and chicken spinal cord 16 .…”

Activity dependent mechanisms of visual map formation - From retinal waves to molecular regulators

“…4B) [22,41,44,62]. This defect can be explained by ectopic branches along the axon and larger terminal arbor in beta2-AChR KO [24] a feature also observed after TTX blockade [59] or Kir2.1 expression [61]. In the beta2-AChR KO, a partial rescue of the TZ size refinement shown in the SC occurs between P7 and P14 [24,62].…”

“…In vivo data however, do not seem to confirm, so far, the involvement of activity for the final topographic positioning of RGCs. Monocular TTX injections, did not impair the retraction from the caudal SC of temporal RGCs [60] and expression of inward-rectifier potassium ion channels (Kir2.1) in the mouse retina (which blocks activity by membrane potential hyperpolarization) did not induce major targeting defects of retinal axons in the SC [61].…”

The assembly of developing motor neurons depends on an interplay between spontaneous activity, type II cadherins and gap junctions

“…1A). Whereas spontaneous electrical activity is known to regulate the late maturation of neuronal circuits (Yamamoto and López-Bendito, 2012), its influence on early developmental events, and interaction with molecular mechanisms has been unclear (Benjumeda et al, 2013;Hanson et al, 2008;Spitzer, 2006). However, rhythmic SA, which occurs in the absence of synaptic input, has previously been recorded from the avian cranial motor nerves at early developmental stages, suggesting a plausible involvement in nucleogenesis (Fortin et al, 1994(Fortin et al, , 1995.…”