Establishment of vagal sensorimotor circuits during fetal development in rats

Abstract

The differentiation of vagal motor neurons and their emerging central relationship with vagal sensory afferents was examined in fetal rats. To identify peripherally projecting sensory and motor neurons, 1,1'-dioctadecyl-3,3,3'3'-tetramethylindocarbocyanine perchlorate (DiI) was inserted into the proximal gut or cervical vagus nerve in fixed preparations. At embryonic day (E) 12, labeled vagal sensory neurons are present in the nodose ganglia and a few sensory axons project into the dorsolateral medulla. Central sensory processes become increasingly prevalent between E13 and E14 but remain restricted to the solitary tract. Vagal motor neurons are first labeled at E13, clustered within a region corresponding to the nucleus ambiguus (NA). Additional motor neurons appear to be migrating toward the NA from the germinal zone of the fourth ventricle. Motor neurons in the dorsal motor nucleus of the vagus (DMV) first project to the gut at E14 and have processes that remain in physical contact with the ventricular zone through E16. Sensory axons emerge from the solitary tract at E15 and project medially through the region of the nucleus of the solitary tract (NST) to end in the ventricular zone. A possible substrate for direct vagovagal, sensorimotor interaction appears at E16, when vagal sensory fibers arborize within the DMV and DMV dendrites extend into the NST. By E18, the vagal nuclei appear remarkably mature. These data suggest specific and discrete targeting of vagal sensory afferents and motor neuron dendrites in fetal rats and define an orderly sequence of developmental events that precedes the establishment of vagal sensorimotor circuits.

Silent Synapses in Developing Rat Nucleus Tractus Solitarii Have AMPA Receptors

“…With this approach, we observed that nearly all excitatory NTS synapses expressed AMPARs from birth. Glutamatergic synapses formed by primary afferent fibers develop before birth, whereas those made by central projections start to develop few days after birth (Rinaman and Levitt, 1993;Rinaman et al, 2000;Zhang and Ashwell, 2001;Lachamp et al, 2002;Rinaman, 2003). Thus, it is likely that synapses investigated in this study by electrophysiology as well as those analyzed by confocal microscopy belongs to the same population (i.e., primary afferent synapses).…”

Visceral sensory inputs to the endocrine hypothalamus

“…The ability of exogenous CCK to engage medullary NST neurons and to suppress food intake in 2-day-old rats means that CCK-1 receptor-mediated activation of vagal afferent inputs to the NST and subsequent processes for recruitment of brainstem circuits that underlie CCK-induced hypophagia already are functional. This is not surprising, because anatomical tracing studies revealed a precocious development of vagal viscerosensory inputs to the NST during embryonic development [144]. In newborn rat pups, exogenous CCK causes a significant increase in the excitability of NST neurons that are synaptically activated by electrical stimulation of the subdiaphragmatic vagus nerve, and the increased sensitivity is blocked by a specific CCK-1 receptor antagonist [145].…”

Ontogeny of hypothalamic-hindbrain feeding control circuits

“…Anatomical and functional analyses indicate that the DVC in rats undergoes an early, largely prenatal assembly and maturation of its primary viscerosensory inputs and vagovagal reflex circuitry (Rinaman, Card, Schwaber, & Miselis, 1989;Rinaman & Levitt, 1993;Shapiro & Miselis, 1985){Shapiro, 1985Rinaman, 1989 #138;Rinaman, 1993#505}(Zhang & Ashwell, 2001a. Conversely, hypothalamic and other central neural inputs to the DVC undergo a significant amount of postnatal maturation, together with significant remodeling of local DVC networks (Kawai & Senba, 2000;Lachamp, Tell, & Kessler, 2002;Rao, Jean, & Kessler, 1997;Vincent & Tell, 1999).…”