Authors: Mayu Takahashi, Yuriko Sugiuchi, Jie Na...

Omnipause neurons (OPNs) in the nucleus raphe interpositus have tonic activity while the eyes are stationary ("fixation") but stop firing immediately before and during saccades. To locate the source of suppression, we analyzed synaptic inputs from the rostral and caudal superior colliculi (SCs) to OPNs by using intracellular recording and staining, and investigated pathways transmitting the inputs in anesthetized cats of both sexes. Electrophysiologically or morphologically identified OPNs received monosynaptic excitation from the rostral SCs with contralateral dominance, and received disynaptic inhibition from the caudal SCs with ipsilateral dominance. Cutting the tectoreticular tract transversely between the contralateral OPN and inhibitory burst neuron (IBN) regions eliminated inhibition from the caudal SCs, but not excitation from the rostral SCs in OPNs. In contrast, a midline section between IBN regions eliminated disynaptic inhibition in OPNs from the caudal SCs but did not affect the monosynaptic excitation from the rostral SCs. Stimulation of the contralateral IBN region evoked monosynaptic inhibition in OPNs, which was facilitated by preconditioning SC stimulation. Three-dimensional reconstruction of HRP-stained cells revealed that individual OPNs have axons that terminate in the opposite IBN area, while individual IBNs have axon collaterals to the opposite OPN area. These results show that there are differences in the neural circuit from the rostral and caudal SCs to the brainstem premotor circuitry and that IBNs suppress OPNs immediately before and during saccades. Thus, the IBNs, which are activated by caudal SC saccade neurons, shut down OPN firing and help to trigger saccades and suppress ("latch") OPN activity during saccades. Saccades are the fastest eye movements to redirect gaze to an object of interest and bring its image on the fovea for fixation. Burst neurons (BNs) and omnipause neurons (OPNs) which behave reciprocally in the brainstem, are important for saccade generation and fixation. This study investigated unsolved important questions about where these neurons receive command signals and how they interact for initiating saccades from visual fixation. The results show that the rostral superior colliculi (SCs) excite OPNs monosynaptically for fixation, whereas the caudal SCs monosynaptically excite inhibitory BNs, which then directly inhibit OPNs for the initiation of saccades. This inhibition from the caudal SCs may account for the omnipause behavior of OPNs for initiation and maintenance of saccades in all directions.

Topics: Animals; Brain Stem; Cats; Female; Fixation, Ocular; Inhibitory Postsynaptic Potentials; Male; Microelectrodes; Nerve Net; Saccades; Superior Colliculi; Synaptic Potentials

PubMed: 34880121
DOI: 10.1523/JNEUROSCI.1731-21.2021

Review

Authors: Iroise Dumontheil, Paul W Burgess, Sarah-Jayne Blakemore...

Information on the development and functions of rostral prefrontal cortex (PFC), or Brodmann area 10, has been gathered from different fields, from anatomical development to functional neuroimaging in adults, and put forward in relation to three particular cognitive and behavioural disorders. Rostral PFC is larger and has a lower cell density in humans than in other primates. It also has a large number of dendritic spines per cell and numerous connections to the supramodal cortex. These characteristics suggest that rostral PFC is likely to support processes of integration or coordination of inputs that are particularly developed in humans. The development of rostral PFC is prolonged, with decreases in grey matter and synaptic density continuing into adolescence. Functions attributed to rostral PFC, such as prospective memory, seem similarly to follow a prolonged development until adulthood. Neuroimaging studies have generally found a reduced recruitment of rostral PFC, for example in tasks requiring response inhibition, in adults compared with children or adolescents, which is consistent with maturation of grey matter. The examples of autism, attention-deficit-hyperactivity disorder, and schizophrenia show that rostral PFC could be affected in several disorders as a result of the susceptibility of its prolonged maturation to developmental abnormalities.

Topics: Adolescent; Cell Count; Child; Child Behavior Disorders; Child, Preschool; Cognition Disorders; Dendrites; Humans; Intelligence; Magnetic Resonance Imaging; Memory Disorders; Prefrontal Cortex; Severity of Illness Index; Synapses

PubMed: 18190537
DOI: 10.1111/j.1469-8749.2008.02026.x

Authors: Florence Netzer, Caroline Sévoz-Couche

BACKGROUND AND PURPOSE

Activation of the defence reaction inhibits the baroreflex response via the intermediate rostro-ventromedial medulla (B3 raphé) and nucleus tractus solitarius (NTS). Our aim was to determine whether and how baroreflex inhibition, induced by the disinhibition of the rostral cuneiform nucleus (part of the defence pathway), involves 5-HT neurons in B3 and 5-HT receptors in the NTS.

EXPERIMENTAL APPROACH

We performed immunohistochemistry and anatomical experiments to determine whether raphé 5-HT cells expressing Fos were directly targeted by the rostral cuneiform nucleus. The effect of blocking raphé 5-HT neurotransmission and NTS 5-HT receptors on cuneiform-induced inhibition of the baroreflex cardiac response were also analysed.

KEY RESULTS

Bicuculline, microinjected into the rostral cuneiform nucleus, induced an increase of double-labelled Fos-5-HT-IR cells in both the lateral paragigantocellular nucleus (LPGi) and raphé magnus. The anterograde tracer Phaseolus vulgaris leucoaggutinin injected into the rostral cuneiform nucleus revealed a dense projection to the LPGi but not raphé magnus. Cuneiform-induced baroreflex inhibition was prevented by B3 injection of 8-OH-DPAT, a selective 5-HT receptor agonist. Cuneiform disinhibition also failed to inhibit the baroreflex bradycardia after NTS microinjection of the 5-HT receptor antagonist granisetron and in 5-HT receptor knockout mice.

CONCLUSION AND IMPLICATIONS

The rostral cuneiform nucleus participates in the defence inhibition of the baroreflex bradycardia via direct activation of the LPGi and via a projection to the raphé magnus to activate NTS 5-HT receptors and inhibit second-order baroreflex neurons. These data bring new insights in primary and secondary mechanisms involved in vital baroreflex prevention during stress.

Topics: Animals; Baroreflex; Mesencephalon; Mice; Midbrain Reticular Formation; Rats; Rats, Sprague-Dawley; Serotonin; Solitary Nucleus

PubMed: 33543768
DOI: 10.1111/bph.15406

Review

Authors: John C O'Donnell, Kritika S Katiyar, Kate V Panzer...

New neurons are integrated into the circuitry of the olfactory bulb throughout the lifespan in the mammalian brain-including in humans. These new neurons are born in the subventricular zone and subsequently mature as they are guided over long distances via the rostral migratory stream through mechanisms we are only just beginning to understand. Regeneration after brain injury is very limited, and although some neuroblasts from the rostral migratory stream will leave the path and migrate toward cortical lesion sites, this neuronal replacement is generally not sustained and therefore does not provide enough new neurons to alleviate functional deficits. Using newly discovered microtissue engineering techniques, we have built the first self-contained, implantable constructs that mimic the architecture and function of the rostral migratory stream. This engineered microtissue emulates the dense cord-like bundles of astrocytic somata and processes that are the hallmark anatomical feature of the glial tube. As such, our living microtissue-engineered rostral migratory stream can serve as an in vitro test bed for unlocking the secrets of neuroblast migration and maturation, and may potentially serve as a living transplantable construct derived from a patient's own cells that can redirect their own neuroblasts into lesion sites for sustained neuronal replacement following brain injury or neurodegenerative disease. In this paper, we summarize the development of fabrication methods for this microtissue-engineered rostral migratory stream and provide proof-of-principle evidence that it promotes and directs migration of immature neurons.

PubMed: 30106034
DOI: 10.4103/1673-5374.235215

Authors: Eileen Nguyen, Kelly M Smith, Nathan Cramer...

In perilous and stressful situations, the ability to suppress pain can be critical for survival. The rostral ventromedial medulla contains neurons that robustly inhibit nocioception at the level of the spinal cord through a top-down modulatory pathway. Although much is known about the role of the rostral ventromedial medulla in the inhibition of pain, the precise ability to directly manipulate pain-inhibitory neurons in the rostral ventromedial medulla has never been achieved. We now expose a cellular circuit that inhibits nocioception and itch in mice. Through a combination of molecular, tracing and behavioural approaches, we found that rostral ventromedial medulla neurons containing the kappa-opioid receptor inhibit itch and nocioception. With chemogenetic inhibition, we uncovered that these neurons are required for stress-induced analgesia. Using intersectional chemogenetic and pharmacological approaches, we determined that rostral ventromedial medulla kappa-opioid receptor neurons inhibit nocioception and itch through a descending circuit. Lastly, we identified a dynorphinergic pathway arising from the periaqueductal grey that modulates nociception within the rostral ventromedial medulla. These discoveries highlight a distinct population of rostral ventromedial medulla neurons capable of broadly and robustly inhibiting itch and nocioception.

Topics: Animals; Medulla Oblongata; Mice; Neurons; Pain; Pruritus; Receptors, Opioid, kappa

PubMed: 35598161
DOI: 10.1093/brain/awac189

Review

Authors: Earl Carstens, Tasuku Akiyama

This chapter summarizes recent findings regarding the central transmission of acute and chronic itch. Itch is transduced by cutaneous pruriceptors that transmit signals to neurons in the superficial spinal cord. Spinal itch-signaling circuits utilize several neuropeptides whose receptors represent novel targets to block itch transmission. Itch is relieved by scratching, which activates spinal interneurons to inhibit itch-transmitting neurons. Spinal itch transmission is also thought to be modulated by descending pathways. Itch is transmitted rostrally via ascending pathways to activate a variety of brain regions involved in sensory discrimination of affective and motor responses to itch. The pathophysiological mechanisms of chronic itch are poorly understood but likely involve sensitization of itch-signaling pathways and/or dysfunction of itch-inhibitory circuits. Improved understanding of central itch mechanisms has identified a number of novel targets for the development of antipruritic treatment strategies.

Topics: Acute Disease; Brain; Chronic Disease; Humans; Interneurons; Neural Pathways; Neurons; Pruritus; Signal Transduction; Skin; Spinal Cord

PubMed: 27578065
DOI: 10.1159/000446011