title: Physiological and morphological properties of Dbx1-derived respiratory neurons in the pre-Botzinger complex of neonatal mice.
abstract: Breathing in mammals depends on an inspiratory-related rhythm that is generated by glutamatergic neurons in the pre-Bötzinger complex (preBötC) of the lower brainstem. A substantial subset of putative rhythm-generating preBötC neurons derive from a single genetic line that expresses the transcription factor Dbx1, but the cellular mechanisms of rhythmogenesis remain incompletely understood. To elucidate these mechanisms, we carried out a comparative analysis of Dbx1-expressing neurons (Dbx1(+)) and non-Dbx1-derived (Dbx1(-)) neurons in the preBötC. Whole-cell recordings in rhythmically active newborn mouse slice preparations showed that Dbx1(+) neurons activate earlier in the respiratory cycle and discharge greater magnitude inspiratory bursts compared with Dbx1(-) neurons. Furthermore, Dbx1(+) neurons required less input current to discharge spikes (rheobase) in the context of network activity. The expression of intrinsic membrane properties indicative of A-current (IA) and hyperpolarization-activated current (Ih) tended to be mutually exclusive in Dbx1(+) neurons. In contrast, there was no such relationship in the expression of currents IA and Ih in Dbx1(-) neurons. Confocal imaging and digital morphological reconstruction of recorded neurons revealed dendritic spines on Dbx1(-) neurons, but Dbx1(+) neurons were spineless. The morphology of Dbx1(+) neurons was largely confined to the transverse plane, whereas Dbx1(-) neurons projected dendrites to a greater extent in the parasagittal plane. The putative rhythmogenic nature of Dbx1(+) neurons may be attributable, in part, to a higher level of intrinsic excitability in the context of network synaptic activity. Furthermore, Dbx1(+) neuronal morphology may facilitate temporal summation and integration of local synaptic inputs from other Dbx1(+) neurons, taking place largely in the dendrites, which could be important for initiating and maintaining bursts and synchronizing activity during the inspiratory phase.
authors: Department of Applied Science, McGlothlin-Street Hall, Room 318, The College of William & Mary, Williamsburg, VA 23187-8795, USA. cadeln@wm.edu
authors: Maria Cristina D
authors: MC
authors: Picardo
authors: Krishanthi T H
authors: KT
authors: Weragalaarachchi
authors: Victoria T
authors: VT
authors: Akins
authors: Christopher A
authors: CA
authors: Del Negro
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001933:Brain Stem / Q000166:cytology / Q000502:physiology*; D018398:Homeodomain Proteins / Q000502:physiology*; D066298:In Vitro Techniques; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000502:physiology*; D012119:Respiration
chemical_list: C103403:Dbx1 protein, mouse; D018398:Homeodomain Proteins