Kölliker–Fuse GABAergic and glutamatergic neurons project to distinct targets

Abstract

The Kölliker-Fuse nucleus (KF) is known primarily for its respiratory function as the “pneumotaxic center” or “pontine respiratory group.” Considered part of the parabrachial (PB) complex, KF contains glutamatergic neurons that project to respiratory-related targets in the medulla and spinal cord (Yokota, Oka, Tsumori, Nakamura, & Yasui, 2007). Here we describe an unexpected population of neurons in the caudal KF and adjacent lateral crescent subnucleus (PBlc), which are γ-aminobutyric acid (GABA)ergic and have an entirely different pattern of projections than glutamatergic KF neurons. First, immunofluorescence, in situ hybridization, and Cre-reporter labeling revealed that many of these GABAergic neurons express FoxP2 in both rats and mice. Next, using Cre-dependent axonal tracing in Vgat-IRES-Cre and Vglut2-IRES-Cre mice, we identified different projection patterns from GABAergic and glutamatergic neurons in this region. GABAergic neurons in KF and PBlc project heavily and almost exclusively to trigeminal sensory nuclei, with minimal projections to cardiorespiratory nuclei in the brainstem, and none to the spinal cord. In contrast, glutamatergic KF neurons project heavily to the autonomic, respiratory, and motor regions of the medulla and spinal cord previously identified as efferent targets mediating KF cardiorespiratory effects. These findings identify a novel, GABAergic subpopulation of KF/PB neurons with a distinct efferent projection pattern targeting the brainstem trigeminal sensory system. Rather than regulating breathing, we propose that these neurons influence vibrissal sensorimotor function.

Intracerebroventricular streptozotocin‐induced Alzheimer's disease‐like sleep disorders in rats: Role of the GABAergic system in the parabrachial complex

“…Based on the effects of glutamatergic and GABAergic neurons in the PBN on sleep‐wake regulation, we evaluated neuronal activity in the PBN to explore the mechanisms of changes in states of behavioral arousal in STZ‐injected rats. Consistent with previous reports, glutamatergic neurons were distributed extensively in the whole PBN, and GABAergic neurons were distributed in the caudal part of the PBN. The density of v‐GLUT2+ neurons and density of GAD+ neurons in the caudal part of the PBN (−9.3 mm from bregma) were unaffected by the STZ injection.…”

Efferent projections of excitatory and inhibitory preBötzinger Complex neurons

“…Sheep anti‐FoxP2 antibody (R & D Systems, Cat# AF5647, RRID: AB_2107133) was raised against a recombinant peptide sequence from human FoxP2 (A640‐E715) and affinity purified. Immunolabeling in the mouse brainstem using this primary antibody resulted in a pattern that is similar to Foxp2 mRNA labeling as depicted in the Allen Brain Atlas (Allen Mouse Brain Atlas, RRID:SCR_002978; Geerling, Yokota, Rukhadze, Roe, & Chamberlin, ), and a Western blot from the manufacturer indicates that the antibody detects a single band at ∼90 kDa corresponding to FoxP2 in human glioblastoma lysate.…”

“…Different subtypes of neurons in the parabrachial nuclei and KF modulate inspiratory and expiratory duration, control the transition between inspiration to expiration, and may play a role in the generation of post-inspiratory activity (Dutschmann & Dick, 2012). The parabrachial nuclei and KF are reciprocally connected to many breathing CPG regions including VRG and NTS (Geerling et al, 2017;Yokota, Kaur, VanderHorst, Saper, & Chamberlin, 2015;Yokota, Oka, Tsumori, Nakamura, & Yasui, 2007). In addition to their reciprocal connectivity with the preB€ otC, these nuclei project rostrally to suprapontine regions including amygdala, cortex, bed nucleus of the stria terminalis, and hypothalamus (Krukoff, Harris, & Jhamandas, 1993), providing an ascending pathway for breathingrelated signals to influence higher-order functions, including emotion and cognition.…”

Differential impact of two critical respiratory centres in opioid‐induced respiratory depression in awake mice

“…; Geerling et al . ). Following the above hypothesis, in the KF‐MOR‐cKO mice, the KF neurons are not inhibited by morphine and appear to provide enough regulatory input to the preBötC and other respiratory centres to somewhat stabilize the rate and patterning of the respiratory motor output.…”