Review of the cytology and connections of the lateral habenula, an avatar of adaptive behaving

Abstract

The cytology and connections of the lateral habenula (LHb) are reviewed. The habenula is first introduced, after which the cytology of the LHb is discussed mainly with reference to cell types, general topography and descriptions of subnuclei. An overview of LHb afferent connections is given followed by some details about the projections to LHb from a number of structures. An overview of lateral habenula efferent connections is given followed by some details about the projections from LHb to a number of structures. In considering the afferent and efferent connections of the LHb some attention is given to the relative validity of regarding it as a bi-partite structure featuring 'limbic' and 'pallidal' parts. The paper ends with some concluding remarks about the relative place of the LHb in adaptive behaving.

Keywords: Dopamine; Dorsal raphe; Lateral hypothalamus; Lateral preoptic area; Median raphe; Substantia nigra compacta; Ventral tegmental area; ventral pallidum.

Figure 1

Micrographs illustrating a PHA-L injection into the caudal part of the lateral preoptic area (A, inset in A shows additonal landmarks) and several frontal sections cut through the habenula (Hb) in rostrocaudal sequence from B to E. Outlines of lateral habenula subnuclei have been approximated on the contralateral side relative to the injection according to the original drawings of Andres et al. (1999). Note also the locations of the attachments of the roof of the dorsal part of the third ventricle (arIII). Panels B–E show anterograde labeling (brown reaction product) from the injection site shown in A. Sparse anterograde labeling is observed in the LHb contralateral to the injection. Note on the side ipsilateral to the injection that dense labeling is present in LHb, but not in MHb, and spreads across its entire mediolateral extent, although the labeling is ‘patchy’ with some areas being relatively devoid of reaction product (* and **). Areas exhibiting reaction product lacunae do not correspond precisely or consistently to subnuclei, however. For example, central area with lesser density of reaction product in B and C (*) has no obvious subnuclear correspondence. That in D –F may imprecisely approximate LHbMC and LHbMPc. A ventrolateral area lacking dense labeling (**) would seem to include LHbLO, consistent with the findings of Kowski et al. (2008), but is invariably much larger than that subnucleus. Alternatively, dense labeling appears to fill LHbLPc and LHbLMg. Additional abbreviations: arIII – attachment of the roof of the third ventricle; f – fornix; fr – fasciculus retroflexux; LPO – lateral preoptic area; LHbLB – basal subnucleus of LHbL; LHbLMc – magnocellular subnucleus of LHbL; LHbLMg – marginal subnucleus of LHbL; LHbLO – oval subnucleus of LHbL; LHbLPc – parvocellular nucleus of LHbL; LHbMA – anterior nucleus of LHbM; LHbMC – central subnucleus of LHbM; LHbMMg – marginal subnucleus of LHbM; LHbMPc – parvocellular subnucleus of LHbM; LHbMS – superior subnucleus of LHbM; MHb – medial habenula; ot – optic tract; PV – paraventricular nucleus of the thalamus; sm – stria medullaris; v – ventricle; IIId = dorsal part of the third ventricle. Scale bar: 1 mm

Figure 2

Micrographs illustrating additional injections of PHA-L into the lateral preoptic area-lateral hypothalamus continuum, one more rostral (A–C) and one more caudal (D–F) than the PHA-L injection shown in Figure 1. Injection sites are shown in the insets in A and D and frontal sections through the habenula are shown at rostral (A and D), middle (B and E) and caudal (C and F) levels. The medial habenula (MHb), lateral habenula (LHb) and stria medullaris (sm) are outlined for reference on one side of the midline. Subnuclei have been left out. Note also the locations of the attachments of the roof of the dorsal part of the third ventricle (arIII). Panels A–C and D–F show anterograde labeling resulting from injections of PHA-L into the rostralmost part of LPO where it transitions to ventral pallidum (A–C) and the rostralmost dorsolateral part of the lateral hypothalamus (D–F). Both injections produced sparse anterograde labeling in the LHb contralateral to the injection. Note in panels A–C, however, that dense labeling (black reaction product) on the side ipsilateral to the injection is present in LHb, but not in MHb, and spreads into the lateral half of the LHb as previously reported by Kowski et al. (2008) as marked by ** in B. Lacunae in the immunolabeling in B and C, the latter possibly corresponding to the position of LHbLO. Alternatively, in panels D–F ipsilateral labeling spreads densely, but in a ‘patchy’ disposition, across the entire LHb. In D, a central area in LHbL relatively devoid of labeling can be seen (*) as can a spread of dense labeling across dorsal parts of LHb curving around to its lateral parts (**). A small lacuna in the labeling of unclear correspondence, possibly part of the LHbMC/LHbMPc complex is also evident (* in E). Additional abbreviations: ac – anterior commissure; arIII – attachment of the roof of the third ventricle; EPN – entorpeduncular nucleus; f – fornix; fr – fasciculus retroflexux; LH – lateral hypothalamus; LHb – lateral habenula; MHb – medial habenula; ot –optic tract; PV – paraventricular nucleus of the thalamus; sm – stria medullaris; v – ventricle; VP – ventral pallidum; IIId = dorsal part of the third ventricle. Scale bar 1 mm.

Figure 3

Diagram of a cross-section through about the middle of the lateral habenula (LHb) illustrating the two ways that it has been conceptualized. On the right, LHb is shown comprising two divisions, a medial ‘limbic’ part (LHbM) and a lateral ‘pallidal’ part (LHbL). Various axonal projections are described as preferentially arising or terminating in LHbM or LHbL, although, as developed in the text, this is strictly true of but few of them. Subnuclei are depicted on the left side of the diagram. Upon discovery of the subnuclei, it was anticipated that they would reflect functional and connectional compartmentation of the LHb, but this has been realized only in small part, mainly as pertains to LHbMC and LHbMPc (green), which are small-celled, project preferentially to the raphe nuclei and receive input enriched in tyrosine hydroxylase immunoreactivity. Functional and connectional correlates are much more difficult to relate to other LHb subnuclei. Note on the left that subnuclei representing LHbL and LHbM are separated by a heavier, finely stippled line and, at this rostrocaudal level, only eight of ten LHb subnuclei are represented. Additional color codes: dark gray – stria medullaris (sm) ; light gray – medial habenula (MHb). Other abbreviations: LHbLMc – magnocellular subnucleus of the lateral division of the LHb; LHbLMg – marginal subnucleus of the lateral division of the LHb; LHbO – oval subnucleus of the lateral division of the LHb; LHbPc – parvocellular subnucleus of the lateral division of the LHb; LHbMC – central subnucleus of the medial division of the LHb; LHbMMg – marginal subnucleus of the medial division of the LHb; LHbMPc – parvocellular subnucleus of the medial division of the LHb; LHbMS – superior subnucleus of the medial division of the LHb.