Connections of the nucleus incertus

Abstract

The nucleus incertus (NI) is a distinct cell group in caudoventral regions of the pontine periventricular gray, adjacent to the ventromedial border of the caudal dorsal tegmental nucleus. Recent interest in the NI stems from evidence that it represents one of the periventricular sites with the highest expression levels of mRNA encoding the type 1 corticotropin-releasing hormone (CRH) receptor, which has a high affinity for naturally occurring CRH, perhaps accounting for some of the extrapituitary actions of the peptide on autonomic and behavioral components of the stress response. However, almost nothing is known about NI function and hodological relationships. In this paper, we present the results of a systematic analysis of NI inputs and outputs using cholera toxin B subunit as a retrograde tracer and Phaseolus vulgaris-leucoagglutinin as an anterograde tracer. Our retrograde tracer experiments indicate that the NI is in a strategic position to integrate information related to behavioral planning (from the prefrontal cortex), lateral habenular processing, hippocampal function, and oculomotor control. Based on its efferent connections, the NI is in a position to exert significant modulating influences on prefrontal and hippocampal cortical activity, and the nucleus is also in a position to influence brain sites known to control locomotor behavior, attentive states, and learning processes. Overall, the present results support the idea that the NI is a distinct region of the pontine periventricular gray, and together with the superior central (median raphé) and interpeduncular nuclei the NI appears to form a midline behavior control network of the brainstem.

Loss of Goosecoid-like and DiGeorge syndrome critical region 14 in interpeduncular nucleus results in altered regulation of rapid eye movement sleep

“…Injection of an anterograde tracer, an adeno-associated viral vector containing the gene for GFP (AAV-GFP), in the IPl of Gscl −/− and Gscl +/+ mice showed dense efferent fibers throughout pontine midline structures, including the MnR, DRN, LDTg, NI, and posterodorsal tegmental nucleus (PDTg) (Fig. 1P), as previously described (8,9,11). Thus, we found no apparent differences between the two genotypes in the afferent and efferent fiber connections to and from the IP, although there were small differences in the number of labeled cells and fibers among all tracer-injected brains because of inevitable differences in the exact locations and amounts of tracer injected.…”

“…The IP is located on the midline in the ventral region of the midbrain-hindbrain transition and is evolutionarily conserved from fish to mammals. It has reciprocal connections with the median raphe nucleus (MnR), dorsal raphe nucleus (DRN), laterodorsal tegmental nucleus (LDTg), and nucleus incertus (NI) (8)(9)(10)(11)(12)(13), which are implicated in the regulation of sleep and wakefulness and the generation of hippocampal theta waves (2,3,14,15). In addition, the IP receives input from the basal forebrain via the fasciculus retroflexus directly or relayed at the medial habenular nucleus.…”

Central relaxin-3 receptor (RXFP3) activation reduces elevated, but not basal, anxiety-like behaviour in C57BL/6J mice

“…The largest population of relaxin-3 expressing neurons is located within the tegmental area known as the nucleus incertus (NI), and these neurons project broadly throughout the brain [15][16][17][18][19]. The neuroanatomy of the relaxin-3/RXFP3 system suggests a broad role as an ascending neuromodulatory network [20,21], akin to the monoamine systems including serotonin, and noradrenaline [22][23][24][25].…”

“…The neuroanatomy of the relaxin-3/RXFP3 system suggests a broad role as an ascending neuromodulatory network [20,21], akin to the monoamine systems including serotonin, and noradrenaline [22][23][24][25]. Anatomical and functional data [15][16][17][18] suggest that relaxin-3/RXFP3 systems may interact directly with monoamine [19,26] and other peptide systems [27][28][29], and/or act at shared downstream limbic and hypothalamic target areas to modulate 'anxiety' and other stress-related responses [30][31][32][33][34].…”

Connections of the lateral hypothalamic area juxtadorsomedial region in the male rat

“…Intriguingly, in a recent study in which sexually inexperienced male rats were exposed to the odors of male and female conspecifics, the male odors activated a significantly higher percentage of GAD 67 -expressing neurons in the MEA (Donato et al, 2010), which, as discussed, has more extensive connections with the LHAjd than with the LHAjp; analysis of Fos activation of GAD 67 neurons in the SUM was not included in the study (Donato et al, 2010). Another well-described input to the SUM originates in the nucleus incertus (NI) and targets differently the SUMl and SUMm such that the NI compact part sends a prominent input to the SUMm and sparse input to the SUMl, whereas for the NI diffuse part the opposite is true (Goto et al, 2001); the NI also sends a prominent projection to the HPF including the dentate gyrus (Goto et al, 2001). Functionally, it is noteworthy that the SUM and NI have a role in the modulation of the hippocampal theta rhythm (Bland, 1986;Kocsis and Vertes, 1994;Vertes and Kocsis, 1997;Kirk, 1998;Pan and McNaughton, 2004;Nunez et al, 2006).…”