title: Structural-functional properties of identified excitatory and inhibitory interneurons within pre-Botzinger complex respiratory microcircuits.
abstract: We comparatively analyzed cellular and circuit properties of identified rhythmic excitatory and inhibitory interneurons within respiratory microcircuits of the neonatal rodent pre-Bötzinger complex (pre-BötC), the structure generating inspiratory rhythm in the brainstem. We combined high-resolution structural-functional imaging, molecular assays for neurotransmitter phenotype identification in conjunction with electrophysiological property phenotyping, and morphological reconstruction of interneurons in neonatal rat and mouse slices in vitro. This approach revealed previously undifferentiated structural-functional features that distinguish excitatory and inhibitory interneuronal populations. We identified distinct subpopulations of pre-BötC glutamatergic, glycinergic, GABAergic, and glycine-GABA coexpressing interneurons. Most commissural pre-BötC inspiratory interneurons were glutamatergic, with a substantial subset exhibiting intrinsic oscillatory bursting properties. Commissural excitatory interneurons projected with nearly planar trajectories to the contralateral pre-BötC, many also with axon collaterals to areas containing inspiratory hypoglossal (XII) premotoneurons and motoneurons. Inhibitory neurons as characterized in the present study did not exhibit intrinsic oscillatory bursting properties, but were electrophysiologically distinguished by more pronounced spike frequency adaptation properties. Axons of many inhibitory neurons projected ipsilaterally also to regions containing inspiratory XII premotoneurons and motoneurons, whereas a minority of inhibitory neurons had commissural axonal projections. Dendrites of both excitatory and inhibitory interneurons were arborized asymmetrically, primarily in the coronal plane. The dendritic fields of inhibitory neurons were more spatially compact than those of excitatory interneurons. Our results are consistent with the concepts of a compartmental circuit organization, a bilaterally coupled excitatory rhythmogenic kernel, and a role of pre-BötC inhibitory neurons in shaping inspiratory pattern as well as coordinating inspiratory and expiratory activity.
authors: Cellular and Systems Neurobiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors: Hidehiko
authors: H
authors: Koizumi
authors: Naohiro
authors: N
authors: Koshiya
authors: Justine X
authors: JX
authors: Chia
authors: Fang
authors: F
authors: Cao
authors: Joseph
authors: J
authors: Nugent
authors: Ruli
authors: R
authors: Zhang
authors: Jeffrey C
authors: JC
authors: Smith
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling / Q000502:physiology; D003712:Dendrites / Q000502:physiology / Q000648:ultrastructure; D049229:Dendritic Spines / Q000502:physiology / Q000648:ultrastructure; D055724:Electrophysiological Phenomena; D025461:Feedback, Physiological / Q000502:physiology; D005260:Female; D018698:Glutamic Acid / Q000502:physiology; D005998:Glycine / Q000502:physiology; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007395:Interneurons / Q000502:physiology*; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology; D009415:Nerve Net / Q000166:cytology / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D015656:Respiratory Mechanics / Q000502:physiology; D012143:Respiratory Physiological Phenomena; D056969:Voltage-Sensitive Dye Imaging; D005680:gamma-Aminobutyric Acid / Q000502:physiology
chemical_list: D002121:Calcium Channel Blockers; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D005998:Glycine