Looping circuit: a novel mechanism for prolonged spontaneous [Ca2+]i increases in developing embryonic mouse brainstem

J Physiol. 2014 Feb 15;592(4):711-27. doi: 10.1113/jphysiol.2013.265892. Epub 2013 Dec 23.

Abstract

Most cells maintain [Ca(2+)]i at extremely low levels; calcium entry usually occurs briefly, and within seconds it is cleared. However, at embryonic day 12.5 in the mouse brainstem, trains of spontaneous events occur with [Ca(2+)]i staying close to peak value, well above baseline, for minutes; we termed this 'bash bursts'. Here, we investigate the mechanism of this unusual activity using calcium imaging and electrophysiology. Bash bursts are triggered by an event originating at the mid-line of the rostral hindbrain and are usually the result of that event propagating repeatedly along a defined circular path. The looping circuit can either encompass both the midbrain and hindbrain or remain in the hindbrain only, and the type of loop determines the duration of a single lap time, 5 or 3 s, respectively. Bash bursts are supported by high membrane excitability of mid-line cells and are regulated by persistent inward 'window current' at rest, contributing to spontaneous activity. This looping circuit is an effective means for increasing [Ca(2+)]i at brief, regular intervals. Bash bursts disappear by embryonic day 13.5 via alteration of the looping circuit, curtailing the short epoch of bash bursts. The resulting sustained [Ca(2+)]i may influence development of raphe serotonergic and ventral tegmental dopaminergic neurons by modulating gene expression.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Action Potentials*
  • Animals
  • Brain Stem / embryology
  • Brain Stem / metabolism
  • Brain Stem / physiology*
  • Calcium / metabolism*
  • Calcium Signaling*
  • Mice

Substances

  • Calcium