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Nature Neuroscience Aug 2022
Topics: Raphe Nuclei
PubMed: 35915174
DOI: 10.1038/s41593-022-01142-1 -
ELife Jun 2023Opioids depress breathing by inhibition of interconnected respiratory nuclei in the pons and medulla. Mu opioid receptor (MOR) agonists directly hyperpolarize a...
Opioids depress breathing by inhibition of interconnected respiratory nuclei in the pons and medulla. Mu opioid receptor (MOR) agonists directly hyperpolarize a population of neurons in the dorsolateral pons, particularly the Kölliker-Fuse (KF) nucleus, that are key mediators of opioid-induced respiratory depression. However, the projection target and synaptic connections of MOR-expressing KF neurons are unknown. Here, we used retrograde labeling and brain slice electrophysiology to determine that MOR-expressing KF neurons project to respiratory nuclei in the ventrolateral medulla, including the preBötzinger complex (preBötC) and rostral ventral respiratory group (rVRG). These medullary-projecting, MOR-expressing dorsolateral pontine neurons express FoxP2 and are distinct from calcitonin gene-related peptide-expressing lateral parabrachial neurons. Furthermore, dorsolateral pontine neurons release glutamate onto excitatory preBötC and rVRG neurons via monosynaptic projections, which is inhibited by presynaptic opioid receptors. Surprisingly, the majority of excitatory preBötC and rVRG neurons receiving MOR-sensitive glutamatergic synaptic input from the dorsolateral pons are themselves hyperpolarized by opioids, suggesting a selective opioid-sensitive circuit from the KF to the ventrolateral medulla. Opioids inhibit this excitatory pontomedullary respiratory circuit by three distinct mechanisms-somatodendritic MORs on dorsolateral pontine and ventrolateral medullary neurons and presynaptic MORs on dorsolateral pontine neuron terminals in the ventrolateral medulla-all of which could contribute to opioid-induced respiratory depression.
Topics: Analgesics, Opioid; Medulla Oblongata; Neurons; Pons; Respiration
PubMed: 37314062
DOI: 10.7554/eLife.81119 -
Neuron May 2023In this issue of Neuron, Xiao et al. reported that inhibitory and excitatory neurons in the pontine central gray encode and transmit opposite valences of sensory...
In this issue of Neuron, Xiao et al. reported that inhibitory and excitatory neurons in the pontine central gray encode and transmit opposite valences of sensory stimuli through parallel circuits to a distributed brain network.
Topics: Pons; Neurons; Pontine Tegmentum; Cerebellar Nuclei
PubMed: 37141860
DOI: 10.1016/j.neuron.2023.04.009 -
Communications Biology Jun 2022Knowledge of the neural underpinnings of processing sad information and how it differs in people with depression could elucidate the neural mechanisms perpetuating sad...
Knowledge of the neural underpinnings of processing sad information and how it differs in people with depression could elucidate the neural mechanisms perpetuating sad mood in depression. Here, we conduct a 7 T fMRI study to delineate the neural correlates involved only in processing sad information, including pons, amygdala, and corticolimbic regions. We then conduct a 3 T fMRI study to examine the resting-state connectivity in another sample of people with and without depression. Only clinically depressed people demonstrate hyperactive amygdala-pons connectivity. Furthermore, this connectivity is related to depression symptom severity and is a significant indicator of depression. We speculate that visual sad information reinforces depressed mood and stimulates the pons, strengthening the amygdala-pons connectivity. The relationship between this connectivity and depressive symptom severity suggests that guiding one's visual attention and processing of sad information may benefit mood regulation.
Topics: Amygdala; Depression; Emotions; Humans; Magnetic Resonance Imaging; Pons
PubMed: 35688901
DOI: 10.1038/s42003-022-03463-0 -
Nature Jan 2024Survival requires the selection of appropriate behaviour in response to threats, and dysregulated defensive reactions are associated with psychiatric illnesses such as...
Survival requires the selection of appropriate behaviour in response to threats, and dysregulated defensive reactions are associated with psychiatric illnesses such as post-traumatic stress and panic disorder. Threat-induced behaviours, including freezing and flight, are controlled by neuronal circuits in the central amygdala (CeA); however, the source of neuronal excitation of the CeA that contributes to high-intensity defensive responses is unknown. Here we used a combination of neuroanatomical mapping, in vivo calcium imaging, functional manipulations and electrophysiology to characterize a previously unknown projection from the dorsal peduncular (DP) prefrontal cortex to the CeA. DP-to-CeA neurons are glutamatergic and specifically target the medial CeA, the main amygdalar output nucleus mediating conditioned responses to threat. Using a behavioural paradigm that elicits both conditioned freezing and flight, we found that CeA-projecting DP neurons are activated by high-intensity threats in a context-dependent manner. Functional manipulations revealed that the DP-to-CeA pathway is necessary and sufficient for both avoidance behaviour and flight. Furthermore, we found that DP neurons synapse onto neurons within the medial CeA that project to midbrain flight centres. These results elucidate a non-canonical top-down pathway regulating defensive responses.
Topics: Avoidance Learning; Central Amygdaloid Nucleus; Neurons; Prefrontal Cortex; Excitatory Amino Acid Agents; Glutamic Acid; Neural Pathways; Calcium; Electrophysiology; Pons
PubMed: 38233522
DOI: 10.1038/s41586-023-06912-w -
Trends in Neurosciences Nov 2022A shared mechanism across species heralds the arrival of self-generated sensations, helping the brain to anticipate, and therefore distinguish, self-generated from... (Review)
Review
A shared mechanism across species heralds the arrival of self-generated sensations, helping the brain to anticipate, and therefore distinguish, self-generated from externally generated sensations. In mammals, this sensory prediction mechanism is supported by communication within a cortico-ponto-cerebellar-thalamo-cortical loop. Schizophrenia is associated with impaired sensory prediction as well as abnormal structural and functional connections between nodes in this circuit. Despite the pons' principal role in relaying and processing sensory information passed from the cortex to cerebellum, few studies have examined pons connectivity in schizophrenia. Here, we first briefly describe how the pons contributes to sensory prediction. We then summarize schizophrenia-related abnormalities in the cortico-ponto-cerebellar-thalamo-cortical loop, emphasizing the dearth of research on the pons relative to thalamic and cerebellar connections. We conclude with recommendations for advancing our understanding of how the pons relates to sensory prediction failures in schizophrenia.
Topics: Humans; Schizophrenia; Thalamus; Cerebral Cortex; Pons; Cerebellum; Magnetic Resonance Imaging; Neural Pathways
PubMed: 36123224
DOI: 10.1016/j.tins.2022.08.008 -
World Neurosurgery Mar 2022The decision-making process surrounding resection of arteriovenous malformations (AVMs) in proximity to vital brainstem structures is a complex topic. Intricate... (Review)
Review
BACKGROUND
The decision-making process surrounding resection of arteriovenous malformations (AVMs) in proximity to vital brainstem structures is a complex topic. Intricate vasculature in the setting of exquisite brainstem eloquence creates a high-risk operative landscape with the potential for devastating complications. Effective resections are driven by mastery of the relevant operative anatomy, preservation of pertinent vasculature, and technical experience and acumen.
METHODS
This article provides a narrative literature review on the resection of brainstem AVMs.
RESULTS
Operative anatomy and approaches to AVMs of the midbrain (anterior/posterior), pons (anterior/lateral), and medulla (anterior/lateral) are discussed herein, with a focus on pearls and pitfalls for minimizing complications during resection.
CONCLUSIONS
Careful consideration of the patient's clinical background, the natural history of the lesion, and expertise of the treating surgeon are paramount for improving the natural course of brainstem AVMs.
Topics: Brain Stem; Embolization, Therapeutic; Humans; Intracranial Arteriovenous Malformations; Microsurgery; Pons; Treatment Outcome
PubMed: 35255634
DOI: 10.1016/j.wneu.2021.08.120 -
Journal of Ultrasound in Medicine :... Jan 2021To investigate the pons anteroposterior diameter (APD) and cerebellar vermis craniocaudal diameter (CCD) of fetuses with Down syndrome (DS). (Observational Study)
Observational Study
OBJECTIVES
To investigate the pons anteroposterior diameter (APD) and cerebellar vermis craniocaudal diameter (CCD) of fetuses with Down syndrome (DS).
METHODS
This was a prospective observational study including 200 low-risk pregnancies and 18 pregnancies with fetuses who had DS. A midsagittal view was obtained to measure the pons APD and cerebellar vermis CCD. Gestational age-related 5th, mean, and 95th percentiles for the pons APD and cerebellar vermis CCD between 18 and 32 weeks' gestation were created from the low-risk population. Each measurement of a fetus with DS was plotted on growth charts, and those below the 5th percentile for gestational age were considered small.
RESULTS
The pons APD and cerebellar vermis CCD measurements were below the 5th percentile for gestational age in 7 of the 18 (38.8%) fetuses with DS. Fetuses who had pons APDs below the 5th percentile for gestational age also had cerebellar vermis CCDs below the 5th percentile. Fetuses who had pons and cerebellar vermis measurements below the 5th percentile for gestational age on the initial examination continued to have small measurements during follow-up.
CONCLUSIONS
Fetal pons and cerebellar vermis abnormalities could be observed prenatally in fetuses with DS, which could help in the antenatal counseling and postnatal follow-up of such pregnancies.
Topics: Cerebellar Vermis; Down Syndrome; Female; Fetus; Gestational Age; Humans; Pons; Pregnancy; Ultrasonography, Prenatal
PubMed: 32592425
DOI: 10.1002/jum.15382 -
Nature Communications Jul 2023Rapid-eye-movement (REM) sleep is a distinct behavioral state associated with vivid dreaming and memory processing. Phasic bursts of electrical activity, measurable as...
Rapid-eye-movement (REM) sleep is a distinct behavioral state associated with vivid dreaming and memory processing. Phasic bursts of electrical activity, measurable as spike-like pontine (P)-waves, are a hallmark of REM sleep implicated in memory consolidation. However, the brainstem circuits regulating P-waves, and their interactions with circuits generating REM sleep, remain largely unknown. Here, we show that an excitatory population of dorsomedial medulla (dmM) neurons expressing corticotropin-releasing-hormone (CRH) regulates both REM sleep and P-waves in mice. Calcium imaging showed that dmM CRH neurons are selectively activated during REM sleep and recruited during P-waves, and opto- and chemogenetic experiments revealed that this population promotes REM sleep. Chemogenetic manipulation also induced prolonged changes in P-wave frequency, while brief optogenetic activation reliably triggered P-waves along with transiently accelerated theta oscillations in the electroencephalogram (EEG). Together, these findings anatomically and functionally delineate a common medullary hub for the regulation of both REM sleep and P-waves.
Topics: Mice; Animals; Sleep, REM; Electroencephalography; Pons; Medulla Oblongata; Neurons; Corticotropin-Releasing Hormone; Sleep
PubMed: 37400467
DOI: 10.1038/s41467-023-39496-0 -
The Journal of Comparative Neurology Jul 2022Diverse neurons in the parabrachial nucleus (PB) communicate with widespread brain regions. Despite evidence linking them to a variety of homeostatic functions, it...
Diverse neurons in the parabrachial nucleus (PB) communicate with widespread brain regions. Despite evidence linking them to a variety of homeostatic functions, it remains difficult to determine which PB neurons influence which functions because their subpopulations intermingle extensively. An improved framework for identifying these intermingled subpopulations would help advance our understanding of neural circuit functions linked to this region. Here, we present the foundation of a developmental-genetic ontology that classifies PB neurons based on their intrinsic, molecular features. By combining transcription factor labeling with Cre fate-mapping, we find that the PB is a blend of two, developmentally distinct macropopulations of glutamatergic neurons. Neurons in the first macropopulation express Lmx1b (and, to a lesser extent, Lmx1a) and are mutually exclusive with those in a second macropopulation, which derive from precursors expressing Atoh1. This second, Atoh1-derived macropopulation includes many Foxp2-expressing neurons, but Foxp2 also identifies a subset of Lmx1b-expressing neurons in the Kölliker-Fuse nucleus (KF) and a population of GABAergic neurons ventrolateral to the PB ("caudal KF"). Immediately ventral to the PB, Phox2b-expressing glutamatergic neurons (some coexpressing Lmx1b) occupy the KF, supratrigeminal nucleus, and reticular formation. We show that this molecular framework organizes subsidiary patterns of adult gene expression (including Satb2, Calca, Grp, and Pdyn) and predicts output projections to the amygdala (Lmx1b), hypothalamus (Atoh1), and hindbrain (Phox2b/Lmx1b). Using this molecular ontology to organize, interpret, and communicate PB-related information could accelerate the translation of experimental findings from animal models to human patients.
Topics: Animals; Brain; GABAergic Neurons; Humans; Hypothalamus; Kolliker-Fuse Nucleus; Parabrachial Nucleus; Pons; Transcription Factors
PubMed: 35134251
DOI: 10.1002/cne.25307