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Nature Neuroscience Sep 2023The vast expansion from mossy fibers to cerebellar granule cells (GrC) produces a neural representation that supports functions including associative and internal model...
The vast expansion from mossy fibers to cerebellar granule cells (GrC) produces a neural representation that supports functions including associative and internal model learning. This motif is shared by other cerebellum-like structures and has inspired numerous theoretical models. Less attention has been paid to structures immediately presynaptic to GrC layers, whose architecture can be described as a 'bottleneck' and whose function is not understood. We therefore develop a theory of cerebellum-like structures in conjunction with their afferent pathways that predicts the role of the pontine relay to cerebellum and the glomerular organization of the insect antennal lobe. We highlight a new computational distinction between clustered and distributed neuronal representations that is reflected in the anatomy of these two brain structures. Our theory also reconciles recent observations of correlated GrC activity with theories of nonlinear mixing. More generally, it shows that structured compression followed by random expansion is an efficient architecture for flexible computation.
Topics: Cerebellum; Brain; Pons; Learning; Neurons
PubMed: 37604889
DOI: 10.1038/s41593-023-01403-7 -
Journal of Neurochemistry Jan 2021The Kölliker-Fuse nucleus (KF) is a functionally distinct component of the parabrachial complex, located in the dorsolateral pons of mammals. The KF has a major role in... (Review)
Review
The Kölliker-Fuse nucleus (KF) is a functionally distinct component of the parabrachial complex, located in the dorsolateral pons of mammals. The KF has a major role in respiration and upper airway control. A comprehensive understanding of the KF and its contributions to respiratory function and dysfunction requires an appreciation for its neurochemical characteristics. The goal of this review is to summarize the diverse neurochemical composition of the KF, focusing on the neurotransmitters, neuromodulators, and neuropeptides present. We also include a description of the receptors expressed on KF neurons and transporters involved in each system, as well as their putative roles in respiratory physiology. Finally, we provide a short section reviewing the literature regarding neurochemical changes in the KF in the context of respiratory dysfunction observed in SIDS and Rett syndrome. By over-viewing the current literature on the neurochemical composition of the KF, this review will serve to aid a wide range of topics in the future research into the neural control of respiration in health and disease.
Topics: Animals; Humans; Kolliker-Fuse Nucleus; Respiration
PubMed: 32396650
DOI: 10.1111/jnc.15041 -
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 -
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 -
Current Neurology and Neuroscience... Oct 2018Hemicrania Continua (HC) is a daily and persistent form of headache that is characterized by side-locked pain which is continuous, varies in severity and can be... (Review)
Review
PURPOSE OF REVIEW
Hemicrania Continua (HC) is a daily and persistent form of headache that is characterized by side-locked pain which is continuous, varies in severity and can be associated with conjunctival injection, lacrimation, nasal congestion, rhinorrhea, eyelid edema, forehead or facial sweating and miosis and/or ptosis.
RECENT FINDINGS
Functional imaging studies have shown activation of subcortical structures such as the posterior hypothalamus and dorsal rostral pons, which are known to disinhibit the trigeminal autonomic reflex, a reflex responsible for autonomic outflow through trigeminal efferents. A similar pathway activation is seen in other Trigeminal autonomic cephalalgias (TAC) which solidifies HC as a TAC. While we also discuss promising treatments in our review, more evidence is needed before making them a standard of therapy for HC. This article aims to review the recent research on the diagnosis and clinical management of this potentially underdiagnosed primary headache disorder.
Topics: Headache; Humans; Pons; Trigeminal Autonomic Cephalalgias
PubMed: 30328517
DOI: 10.1007/s11910-018-0899-2 -
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 -
World Neurosurgery Oct 2015Multicentric low-grade gliomas are rare entities that occur in disparate regions of the brain. They can present with distinct pathologic and imaging findings and may...
BACKGROUND
Multicentric low-grade gliomas are rare entities that occur in disparate regions of the brain. They can present with distinct pathologic and imaging findings and may harbor a worse prognosis. We present a case of multicentric low-grade gliomas and highlight their pathogenesis, imaging characteristics, and molecular signatures, with implications for clinical management.
CASE
A 49-year-old man presented with left-sided headaches for 3 months. Magnetic resonance imaging revealed concurrent non-enhancing lesions in the left medial temporal lobe and superior cerebellum. Increased size and the development of contrast enhancement in the temporal lesion promoted a left temporal craniotomy. Pathology revealing a grade II ganglioglioma. Three months later, the cerebellar lesion also acquired new contrast enhancement and was found to be a grade II astrocytoma following a supracerebellar infratentorial approach for resection. At 2 years follow-up, the patient remains clinically stable, receiving adjuvant chemotherapy for new non-enhancing, unresectable pontine lesion.
CONCLUSION
Tumor growth rate, detailed pathologic findings, imaging characteristics, and molecular signatures influence the clinical course of multicentric low-grade gliomas. PDGFRA amplifications and IDH1 wild-type status may act in a concerted fashion to produce an accelerated course of radiologic changes and tumor recurrence, as noted in our case. Additional research is needed to stratify the risk of transformation in patients with multicentric low-grade glioma and to guide management strategies.
Topics: Astrocytoma; Brain Stem Neoplasms; Cerebellar Neoplasms; Cerebellum; Craniotomy; Disease Progression; Ganglioglioma; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Recurrence, Local; Neuroimaging; Neurosurgical Procedures; Pons; Temporal Lobe
PubMed: 26004698
DOI: 10.1016/j.wneu.2015.05.021