Nucleus incertus

Last updated
Surface anatomy of the floor of the Fourth ventricle, with the nucleus incertus labeled 4thfloor.png
Surface anatomy of the floor of the Fourth ventricle, with the nucleus incertus labeled
Nucleus incertus
Identifiers
NeuroLex ID nlx_144477
Anatomical terms of neuroanatomy

The nucleus incertus is a brainstem region of the pontine brainstem, just ventral to the 4th ventricle. [1] The term was coined by George Streeter (Latin for "uncertain nucleus") based on its unknown function at the time to name a group of cells he observed near the midline of the floor of the 4th ventricle. [2] It sometimes called the 'nucleus O'. [3]

The nucleus incertus is a bilateral structure which sits near the brainstem, in front of the nucleus prepositus hypoglossi. [4] It consists of mostly ascending GABAergic projection neurons and glutamatergic neurons [5] which innervate a broad range of forebrain regions involved in behavioural activation.

It is part of the theta network acting as a relay from the reticularis pontis oralis nucleus to the septo-hippocampal system. [6] The stimulation of the nucleus incertus activates the hippocampal theta rhythm and either its lesion or inhibition suppress the theta oscillation induced by brainstem stimulation. [7] The nucleus incertus itself presents theta oscillations coupled to the hippocampal theta rhythm. [8]

In addition to hippocampal theta rhythms, the nucleus incertus is involved in the control of locomotor speed and arousal, [9] response to stress [3] and integrating the vestibulo-ocular reflex and gaze holding with hippocampal navigation. [6]

Neuroanatomy and Neurochemistry

The NI consists of GABAergic and glutamatergic neurons that project widely to other regions of the brain, including the septum, hippocampus, hypothalamus, amygdala, interpeduncular nucleus and prefrontal cortex. [1] One of the defining neurochemical characteristics of NI GABAergic neurons is their expression of relaxin-3, a neuropeptide that acts via the G-protein-coupled receptor, known as RXFP3 in various brain regions, but can also activate RXFP1. The primary effect of RXFP3 receptor activation is the suppression of neuronal activity, which occurs mainly through the opening of M-channels, allowing an outward flow of potassium ions. [4]

The relaxin-3/RXFP3 system has been extensively studied since its discovery in 2002 due to its involvement in stress and arousal-related functions. [5] This peptidergic system is preserved throughout vertebrate evolution and is present in zebrafish and several other species, including human. [6] [7] Relaxin-3 (RLN3) is detected in at least two neuronal clusters in both teleosts and mammals, in the periaqueductal grey (PAG) and the NI. However, while in the teleosts the PAG/RLN3 projections target extensive areas of the forebrain and optic tectum, the NI/RLN3 projection is concentrated in the interpeduncular nucleus. By contrast, in mammals, PAG/RLN3 projections are restricted to the brainstem and diencephalon, while NI/RLN3 projections display a wide pattern of ascending projections to areas ranging from the nearby interpeduncular nucleus to the more distant hippocampus and prefrontal cortex. In both teleosts and mammals, the RLN3 signaling system plays a central role in arousal control. [9] [10]

In addition to relaxin-3, NI GABAergic neurons express other neuromodulators such as cholecystokinin (CCK) and neuromedin-B (NMB). These neurons also express receptors for corticotropin-releasing factor (CRF), orexins (hypocretins), melanin- concentrating hormone (MCH), serotonin (5-HT) and glutamate; and this diverse receptor expression profile suggests that the NI integrates signals from multiple neurotransmitter systems. [11]

Related Research Articles

<span class="mw-page-title-main">Striatum</span> Nucleus in the basal ganglia of the brain

The striatum or corpus striatum is a cluster of interconnected nuclei that make up the largest structure of the subcortical basal ganglia. The striatum is a critical component of the motor and reward systems; receives glutamatergic and dopaminergic inputs from different sources; and serves as the primary input to the rest of the basal ganglia.

<span class="mw-page-title-main">Hippocampus</span> Vertebrate brain region involved in memory consolidation

The hippocampus is a major component of the brain of humans and many other vertebrates. The hippocampus is part of the hippocampal formation in the limbic system. It plays important roles in the consolidation of information from short-term memory to long-term memory, and in spatial memory that enables navigation. In humans, and other primates the hippocampus is located in the archicortex, one of the three regions of allocortex, with neural projections to the neocortex. The hippocampus, as the medial pallium, is a structure found in all vertebrates. In the human brain, the hippocampus proper is one of the components of the hippocampal formation.

<span class="mw-page-title-main">Paraventricular nucleus of hypothalamus</span>

The paraventricular nucleus of hypothalamus is a nucleus in the hypothalamus, that lies next to the third ventricle. Many of its neurons project to the posterior pituitary where they secrete oxytocin, and a smaller amount of vasopressin. Other secretions are corticotropin-releasing hormone (CRH) and thyrotropin-releasing hormone (TRH). CRH and TRH are secreted into the hypophyseal portal system, and target different neurons in the anterior pituitary. Dysfunctions of the PVN can cause hypersomnia in mice. In humans, the dysfunction of the PVN and the other nuclei around it can lead to drowsiness for up to 20 hours per day. The PVN is thought to mediate many diverse functions through different hormones, including osmoregulation, appetite, wakefulness, and the response of the body to stress.

<span class="mw-page-title-main">Ventral tegmental area</span> Group of neurons on the floor of the midbrain

The ventral tegmental area (VTA), also known as the ventral tegmental area of Tsai, or simply ventral tegmentum, is a group of neurons located close to the midline on the floor of the midbrain. The VTA is the origin of the dopaminergic cell bodies of the mesocorticolimbic dopamine system and other dopamine pathways; it is widely implicated in the drug and natural reward circuitry of the brain. The VTA plays an important role in a number of processes, including reward cognition and orgasm, among others, as well as several psychiatric disorders. Neurons in the VTA project to numerous areas of the brain, ranging from the prefrontal cortex to the caudal brainstem and several regions in between.

<span class="mw-page-title-main">Locus coeruleus</span> Stress and panic response centre

The locus coeruleus (LC), also spelled locus caeruleus or locus ceruleus, is a nucleus in the pons of the brainstem involved with physiological responses to stress and panic. It is a part of the reticular activating system in the reticular formation.

<span class="mw-page-title-main">Reticular formation</span> Spinal trigeminal nucleus

The reticular formation is a set of interconnected nuclei in the brainstem that spans from the lower end of the medulla oblongata to the upper end of the midbrain. The neurons of the reticular formation make up a complex set of neural networks in the core of the brainstem. The reticular formation is made up of a diffuse net-like formation of reticular nuclei which is not well-defined. It may be seen as being made up of all the interspersed cells in the brainstem between the more compact and named structures.

<span class="mw-page-title-main">Ventrolateral preoptic nucleus</span> Nucleus of the anterior hypothalamus

The ventrolateral preoptic nucleus (VLPO), also known as the intermediate nucleus of the preoptic area (IPA), is a small cluster of neurons situated in the anterior hypothalamus, sitting just above and to the side of the optic chiasm in the brain of humans and other animals. The brain's sleep-promoting nuclei, together with the ascending arousal system which includes components in the brainstem, hypothalamus and basal forebrain, are the interconnected neural systems which control states of arousal, sleep, and transitions between these two states. The VLPO is active during sleep, particularly during non-rapid eye movement sleep, and releases inhibitory neurotransmitters, mainly GABA and galanin, which inhibit neurons of the ascending arousal system that are involved in wakefulness and arousal. The VLPO is in turn innervated by neurons from several components of the ascending arousal system. The VLPO is activated by the endogenous sleep-promoting substances adenosine and prostaglandin D2. The VLPO is inhibited during wakefulness by the arousal-inducing neurotransmitters norepinephrine and acetylcholine. The role of the VLPO in sleep and wakefulness, and its association with sleep disorders – particularly insomnia and narcolepsy – is a growing area of neuroscience research.

Theta waves generate the theta rhythm, a neural oscillation in the brain that underlies various aspects of cognition and behavior, including learning, memory, and spatial navigation in many animals. It can be recorded using various electrophysiological methods, such as electroencephalogram (EEG), recorded either from inside the brain or from electrodes attached to the scalp.

The zona incerta (ZI) is a horizontally elongated small nucleus that separates the larger subthalamic nucleus from the thalamus. Its connections project extensively over the brain from the cerebral cortex down into the spinal cord.

<span class="mw-page-title-main">Median raphe nucleus</span> Brain region having polygonal, fusiform, piriform neurons

The median raphe nucleus(MRN), also known as the superior central nucleus, is a nucleus in the brainstem composed of polygonal, fusiform, and piriform neurons, which exists rostral to the pontine raphe nucleus. The median raphe nucleus is one of several raphe nuclei that lies on the brainstem midline. It is one of two nuclei that are situated more superior to the others. The second of these nuclei is the dorsal raphe nucleus (DRN). The MRN extends from the lower part of the dorsal raphe nucleus to an approximate position at the decussation of the superior cerebellar peduncle.

<span class="mw-page-title-main">Mossy fiber (hippocampus)</span> Pathway in the hippocampus

In the hippocampus, the mossy fiber pathway consists of unmyelinated axons projecting from granule cells in the dentate gyrus that terminate on modulatory hilar mossy cells and in Cornu Ammonis area 3 (CA3), a region involved in encoding short-term memory. These axons were first described as mossy fibers by Santiago Ramón y Cajal as they displayed varicosities along their lengths that gave them a mossy appearance.

<span class="mw-page-title-main">Median preoptic nucleus</span> Nucleus in the anterior hypothalamus

The median preoptic nucleus is located dorsal to the other three nuclei of the preoptic area of the anterior hypothalamus. The hypothalamus is located just beneath the thalamus, the main sensory relay station of the nervous system, and is considered part of the limbic system, which also includes structures such as the hippocampus and the amygdala. The hypothalamus is highly involved in maintaining homeostasis of the body, and the median preoptic nucleus is no exception, contributing to regulation of blood composition, body temperature, and non-REM sleep.

The trisynaptic circuit or trisynaptic loop is a relay of synaptic transmission in the hippocampus. The trisynaptic circuit is a neural circuit in the hippocampus, which is made up of three major cell groups: granule cells in the dentate gyrus, pyramidal neurons in CA3, and pyramidal neurons in CA1. The hippocampal relay involves 3 main regions within the hippocampus which are classified according to their cell type and projection fibers. The first projection of the hippocampus occurs between the entorhinal cortex (EC) and the dentate gyrus (DG). The entorhinal cortex transmits its signals from the parahippocampal gyrus to the dentate gyrus via granule cell fibers known collectively as the perforant path. The dentate gyrus then synapses on pyramidal cells in CA3 via mossy cell fibers. CA3 then fires to CA1 via Schaffer collaterals which synapse in the subiculum and are carried out through the fornix. Collectively the dentate gyrus, CA1 and CA3 of the hippocampus compose the trisynaptic loop.

<span class="mw-page-title-main">Hippocampus anatomy</span> Component of brain anatomy

Hippocampus anatomy describes the physical aspects and properties of the hippocampus, a neural structure in the medial temporal lobe of the brain. It has a distinctive, curved shape that has been likened to the sea-horse monster of Greek mythology and the ram's horns of Amun in Egyptian mythology. This general layout holds across the full range of mammalian species, from hedgehog to human, although the details vary. For example, in the rat, the two hippocampi look similar to a pair of bananas, joined at the stems. In the human and other primates, the portion of the hippocampus near the base of the temporal lobe is much broader than the part at the top. Due to the three-dimensional curvature of this structure, two-dimensional sections such as shown are commonly seen. Neuroimaging pictures can show a number of different shapes, depending on the angle and location of the cut.

<span class="mw-page-title-main">Medial septal nucleus</span>

The medial septal nucleus (MS) is one of the septal nuclei. Neurons in this nucleus give rise to the bulk of efferents from the septal nuclei. A major projection from the medial septal nucleus terminates in the hippocampal formation.

<span class="mw-page-title-main">Relaxin-3</span>

Relaxin-3 is a neuropeptide that was discovered in 2001, and which is highly conserved in species ranging from flies, fish, rodents and humans. Relaxin-3 is a member and ancestral gene of the relaxin family of peptides, which includes the namesake hormone relaxin which mediates peripheral actions during pregnancy and which was found to relax the pelvic ligament in guinea pigs almost a century ago. The cognate receptor for relaxin-3 is the G-protein coupled receptor RXFP3, however relaxin-3 is pharmacologically able to also cross react with RXFP1 and RXFP3.

<span class="mw-page-title-main">Parabrachial nuclei</span>

The parabrachial nuclei, also known as the parabrachial complex, are a group of nuclei in the dorsolateral pons that surrounds the superior cerebellar peduncle as it enters the brainstem from the cerebellum. They are named from the Latin term for the superior cerebellar peduncle, the brachium conjunctivum. In the human brain, the expansion of the superior cerebellar peduncle expands the parabrachial nuclei, which form a thin strip of grey matter over most of the peduncle. The parabrachial nuclei are typically divided along the lines suggested by Baxter and Olszewski in humans, into a medial parabrachial nucleus and lateral parabrachial nucleus. These have in turn been subdivided into a dozen subnuclei: the superior, dorsal, ventral, internal, external and extreme lateral subnuclei; the lateral crescent and subparabrachial nucleus along the ventrolateral margin of the lateral parabrachial complex; and the medial and external medial subnuclei

The parafacial zone (PZ) is a brain structure located in the brainstem within the medulla oblongata believed to be heavily responsible for non-rapid eye movement (non-REM) sleep regulation, specifically for inducing slow-wave sleep.

<span class="mw-page-title-main">Hippocampus proper</span> Part of the brain of mammals

The hippocampus proper refers to the actual structure of the hippocampus which is made up of four regions or subfields. The subfields CA1, CA2, CA3, and CA4 use the initials of cornu Ammonis, an earlier name of the hippocampus.

The supramammillary nucleus (SuM), or supramammillary area, is a thin layer of cells in the brain that lies above the mammillary bodies. It can be considered part of the hypothalamus and diencephalon. The nucleus can be divided into medial and lateral sections. The medial SuM, or SuMM, is made of smaller cells which release dopamine and give input to the lateral septal nucleus. The lateral SuM, or SuML, is made of larger cells that project to the hippocampus.

References

  1. 1 2 Goto M, Swanson LW, Canteras NS (September 2001). "Connections of the nucleus incertus". The Journal of Comparative Neurology. 438 (1): 86–122. doi:10.1002/cne.1303. PMID   11503154.
  2. Streeter GL (1903). "Anatomy of the floor of the fourth ventricle. (The relations between the surface markings and the underlying structures.)". American Journal of Anatomy. 2 (3): 299–313. doi:10.1002/aja.1000020303. ISSN   1553-0795.
  3. 1 2 Ryan PJ, Ma S, Olucha-Bordonau FE, Gundlach AL (May 2011). "Nucleus incertus--an emerging modulatory role in arousal, stress and memory". Neuroscience and Biobehavioral Reviews. 35 (6): 1326–41. doi:10.1016/j.neubiorev.2011.02.004. PMID   21329721. S2CID   24464719.
  4. 1 2 Cheron, Guy; Ris, Laurence; Cebolla, Ana Maria (2023). "Nucleus incertus provides eye velocity and position signals to the vestibulo-ocular cerebellum: a new perspective of the brainstem–cerebellum–hippocampus network". Frontiers in Systems Neuroscience. 17. doi: 10.3389/fnsys.2023.1180627 . ISSN   1662-5137. PMC   10248067 .
  5. 1 2 Cervera-Ferri A, Rahmani Y, Martínez-Bellver S, Teruel-Martí V, Martínez-Ricós J (May 2012). "Glutamatergic projection from the nucleus incertus to the septohippocampal system". Neuroscience Letters. 517 (2): 71–6. doi:10.1016/j.neulet.2012.04.014. PMID   22521581. S2CID   32163510.
  6. 1 2 3 Teruel-Martí V, Cervera-Ferri A, Nuñez A, Valverde-Navarro AA, Olucha-Bordonau FE, Ruiz-Torner A (July 2008). "Anatomical evidence for a ponto-septal pathway via the nucleus incertus in the rat". Brain Research. 1218: 87–96. doi:10.1016/j.brainres.2008.04.022. PMID   18514169. S2CID   5519042.
  7. 1 2 Nuñez A, Cervera-Ferri A, Olucha-Bordonau F, Ruiz-Torner A, Teruel V (May 2006). "Nucleus incertus contribution to hippocampal theta rhythm generation". The European Journal of Neuroscience. 23 (10): 2731–8. doi:10.1111/j.1460-9568.2006.04797.x. PMID   16817876.
  8. Cervera-Ferri A, Guerrero-Martínez J, Bataller-Mompeán M, Taberner-Cortes A, Martínez-Ricós J, Ruiz-Torner A, Teruel-Martí V (June 2011). "Theta synchronization between the hippocampus and the nucleus incertus in urethane-anesthetized rats". Experimental Brain Research. 211 (2): 177–92. doi:10.1007/s00221-011-2666-3. PMID   21479657. S2CID   23444954.
  9. 1 2 Lu L, Ren Y, Yu T, Liu Z, Wang S, Tan L, et al. (January 2020). "Control of locomotor speed, arousal, and hippocampal theta rhythms by the nucleus incertus". Nature Communications. 11 (1): 262. Bibcode:2020NatCo..11..262L. doi:10.1038/s41467-019-14116-y. PMC   6959274 . PMID   31937768.
  10. Olucha-Bordonau, Francisco E.; Teruel, Vicent; Barcia-González, Jorge; Ruiz-Torner, Amparo; Valverde-Navarro, Alfonso A.; Martínez-Soriano, Francisco (2003-09-08). "Cytoarchitecture and efferent projections of the nucleus incertus of the rat". The Journal of Comparative Neurology. 464 (1): 62–97. doi:10.1002/cne.10774. ISSN   0021-9967. PMID   12866129.
  11. Ryan, Philip J.; Ma, Sherie; Olucha-Bordonau, Francisco E.; Gundlach, Andrew L. (2011-05-01). "Nucleus incertus—An emerging modulatory role in arousal, stress and memory". Neuroscience & Biobehavioral Reviews. 35 (6): 1326–1341. doi:10.1016/j.neubiorev.2011.02.004. ISSN   0149-7634.