Florey Department of Neuroscience and Mental Health - Research Publications
Permanent URI for this collection
Search Results
1 - 3 of 3
-
ItemForebrain projection neurons target functionally diverse respiratory control areas in the midbrain, pons, and medulla oblongata(WILEY, 2021-06)Eupnea is generated by neural circuits located in the ponto-medullary brainstem, but can be modulated by higher brain inputs which contribute to volitional control of breathing and the expression of orofacial behaviors, such as vocalization, sniffing, coughing, and swallowing. Surprisingly, the anatomical organization of descending inputs that connect the forebrain with the brainstem respiratory network remains poorly defined. We hypothesized that descending forebrain projections target multiple distributed respiratory control nuclei across the neuroaxis. To test our hypothesis, we made discrete unilateral microinjections of the retrograde tracer cholera toxin subunit B in the midbrain periaqueductal gray (PAG), the pontine Kölliker-Fuse nucleus (KFn), the medullary Bötzinger complex (BötC), pre-BötC, or caudal midline raphé nuclei. We quantified the regional distribution of retrogradely labeled neurons in the forebrain 12-14 days postinjection. Overall, our data reveal that descending inputs from cortical areas predominantly target the PAG and KFn. Differential forebrain regions innervating the PAG (prefrontal, cingulate cortices, and lateral septum) and KFn (rhinal, piriform, and somatosensory cortices) imply that volitional motor commands for vocalization are specifically relayed via the PAG, while the KFn may receive commands to coordinate breathing with other orofacial behaviors (e.g., sniffing, swallowing). Additionally, we observed that the limbic or autonomic (interoceptive) systems are connected to broadly distributed downstream bulbar respiratory networks. Collectively, these data provide a neural substrate to explain how volitional, state-dependent, and emotional modulation of breathing is regulated by the forebrain.
-
ItemReflex regulation of breathing by the paratrigeminal nucleus via multiple bulbar circuits(SPRINGER HEIDELBERG, 2018-12)Sensory neurons of the jugular vagal ganglia innervate the respiratory tract and project to the poorly studied medullary paratrigeminal nucleus. In the present study, we used neuroanatomical tracing, pharmacology and physiology in guinea pig to investigate the paratrigeminal neural circuits mediating jugular ganglia-evoked respiratory reflexes. Retrogradely traced laryngeal jugular ganglia neurons were largely (> 60%) unmyelinated and expressed the neuropeptide substance P and calcitonin gene-related peptide, although a population (~ 30%) of larger diameter myelinated jugular neurons was defined by the expression of vGlut1. Within the brainstem, vagal afferent terminals were confined to the caudal two-thirds of the paratrigeminal nucleus. Electrical stimulation of the laryngeal mucosa evoked a vagally mediated respiratory slowing that was mimicked by laryngeal capsaicin application. These laryngeal reflexes were modestly reduced by neuropeptide receptor antagonist microinjections into the paratrigeminal nucleus, but abolished by ionotropic glutamate receptor antagonists. D,L-Homocysteic acid microinjections into the paratrigeminal nucleus mimicked the laryngeal-evoked respiratory slowing, whereas capsaicin microinjections evoked a persistent tachypnoea that was insensitive to glutamatergic inhibition but abolished by neuropeptide receptor antagonists. Extensive projections from paratrigeminal neurons were anterogradely traced throughout the pontomedullary respiratory column. Dual retrograde tracing from pontine and ventrolateral medullary termination sites, as well as immunohistochemical staining for calbindin and neurokinin 1 receptors, supported the existence of different subpopulations of paratrigeminal neurons. Collectively, these data provide anatomical and functional evidence for at least two types of post-synaptic paratrigeminal neurons involved in respiratory reflexes, highlighting an unrecognised complexity in sensory processing in this region of the brainstem.
-
ItemNo Preview AvailableDescending forebrain projections targeting respiratory control areas in the midbrain and brainstem of rats(WILEY, 2020-04)Breathing can be voluntarily modulated via descending inputs from the forebrain to evoke respiratory‐related behaviours, such as vocalization, sniffing, swallowing or breath‐holding. Such behaviors require controlled laryngeal adduction and thus, are conducted during the post‐inspiratory phase of respiratory cycle. However, descending pathways that connect forebrain regions with primary post‐inspiratory control areas such as the pontine Kölliker‐Fuse nucleus (KF) and the medullary Bötzinger complex (BötC) remain to be identified. Here, we investigated the topography of forebrain descending projection neurons to a variety of bulbar respiratory nuclei. We locally microinjected the conventional retrograde tracer cholera toxin subunit B (CT‐B, 100–150nL) into the BötC, KF, the pre‐Bötzinger complex (pre‐BötC), the midline raphé nuclei and the midbrain periaqueductal gray (PAG). Twelve days after unilateral CT‐B injections, brains were sectioned (40μm) and immunohistochemically stained with an anti‐CT‐B antibody. The strength of descending projections was qualitatively assessed: as strong (+++), moderate (++) or weak (+) numbers of CT‐B labeled cell bodies. Retrogradely labelled neurons after unilateral injections into the lateral PAG confirmed the predominantly ipsilateral location of strong and moderate descending projection neurons in the cingulate (+++), pre‐limbic (+++), ectorhinal (++), motor (+++) and insular (++) cortices, the lateral septum (++), amygdala (+++) and hypothalamus (+++). In comparison, retrogradely labeled neurons after unilateral KF injection were also found ipsilaterally in the motor (++), prelimbic (++) and insular cortices (+++), the amygdala (++) and hypothalamus (+++). However, amongst all analysed descending target areas, only the KF receives substantial inputs from the ectorhinal (+++) and endopiriform (++) cortices. In addition, the medullary BötC receives weaker inputs from prelimbic (+) and insular (+) cortices and receives moderate inputs from the amygdala and hypothalamus. Descending projection neurons to the pre‐BötC were in accordance with the literature: motor (+) and insular (+) cortices, amygdala (+++) and hypothalamus (++). Finally, descending inputs to the medullary raphé obscurus and raphé magnus nuclei also arose from motor, prelimbic and insular cortices, amygdala and hypothalamus. However, these projections were significantly weaker compared to KF or PAG. The results suggest that descending forebrain projections into respiratory control areas are organized in general pathways that originate from motor, prelimbic and insular cortices as well as the amygdala and hypothalamus. However, only the KF, a key area for the gating of post‐inspiratory activity and respiratory plasticity, receives projections arising from the endopiriform and ectorhinal cortex. The functional implications of these descending control pathways need to be explored in future studies. Support or Funding Information Melbourne Research Scholarship (University of Melbourne) [181858] to PT‐B.