Dorsoventral Arrangement of Lateral Hypothalamus Populations in the Mouse Hypothalamus: a Prosomeric Genoarchitectonic Analysis

Abstract

The lateral hypothalamus (LH) has a heterogeneous cytoarchitectonic organization that has not been elucidated in detail. In this work, we analyzed within the framework of the prosomeric model the differential expression pattern of 59 molecular markers along the ventrodorsal dimension of the medial forebrain bundle in the mouse, considering basal and alar plate subregions of the LH. We found five basal (LH1–LH5) and four alar (LH6–LH9) molecularly distinct sectors of the LH with neuronal cell groups that correlate in topography with previously postulated alar and basal hypothalamic progenitor domains. Most peptidergic populations were restricted to one of these LH sectors though some may have dispersed into a neighboring sector. For instance, histaminergic Hdc-positive neurons were mostly contained within the basal LH3, Nts (neurotensin)- and Tac2 (tachykinin 2)-expressing cells lie strictly within LH4, Hcrt (hypocretin/orexin)-positive and Pmch (pro-melanin-concentrating hormone)-positive neurons appeared within separate LH5 subdivisions, Pnoc (prepronociceptin)-expressing cells were mainly restricted to LH6, and Sst (somatostatin)-positive cells were identified within the LH7 sector. The alar LH9 sector, a component of the Foxg1-positive telencephalo-opto-hypothalamic border region, selectively contained Satb2-expressing cells. Published studies of rodent LH subdivisions have not described the observed pattern. Our genoarchitectonic map should aid in systematic approaches to elucidate LH connectivity and function.

Critical test of the assumption that the hypothalamic entopeduncular nucleus of rodents is homologous with the primate internal pallidum

“…Finally, the subthalamic nucleus (originally lumped together with the pallidal primordia by Spatz, 1921, 1924, 1925) became dissociated from the hypothalamic entopeduncular population, once it was discovered that the former primordium is produced in the retromamillary basal plate region (within the hp1 prosomere of Puelles et al, 2012; this area is identified by columnar authors as ‘supramamillary area’). The subthalamic primordium migrates tangentially dorsalward under the pial surface of the peduncular hypothalamus into its dorsal retrotuberal final position (secondarily covered by the cerebral peduncle), as was concluded from descriptive data (Gilbert, 1935; Papez, 1940; Jiao et al, 2000), and confirmed experimentally by autoradiographic (Altman & Bayer 1986; Keyser, 1972; Marchand et al, 1986) and molecular analysis (Martin et al, 2002, 2004; Puelles et al, 2012; see also Diaz et al, 2023; López‐González et al, 2021; Puelles & Rubenstein, 2015).…”

“…Several other mRNA transcripts typically characterizing the EPV include the transcription factors Arx , Foxp2 , and Meis1 and other genes such as Cbln2 , Chrm3 , Pvalb , Trpc4 , Rgs4 , and Spp1 (Figure 2a,b; Table 3). The EPV is typically aligned dorsoventrally within the Dlx ‐positive subparaventricular band (in longitudinal continuity with the recently defined rostral liminar nucleus [RLi] of the prethalamus, which is also Dlx5/6 ‐ LacZ positive; Díaz et al., 2023; Puelles et al., 2021; EPV, RLi; Figure 1a). The peduncular position of EPV typically coincides roughly with the subpial course of the optic tract (ot; Figures 1c and 3) and is somewhat dorsal relative to the STh in the underlying basal plate (Figures 1b–d and 2b,k) and ventral to its alar companion, the EPD (the optic tract is thus useful for the distinction of the neighboring EPV and EPD formations).…”

“…The alar peduncular hypothalamus is divided dorsoventrally between the Dlx ‐negative paraventricular area and the Dlx ‐positive subparaventricular area (Díaz et al., 2023; Puelles & Rubenstein, 2003; Puelles et al., 2012, 2021; Figure 1a).…”

“…The SPa domain displays a relatively massive rostral part in the terminal hypothalamus (TSPa; encompassing the anterior hypothalamic and suprachiasmatic grisea) and caudally a thinner peduncular part (PSPa; Figure 4a). The PSPa displays superficially the peduncular fibers with the EPV, underlined by a molecularly distinct lateral hypothalamus sector (Díaz et al., 2023), and its periventricular stratum is dorsoventrally thin (Figure 4a). The PSPa is continuous caudally with the Dlx5/6 ‐ LacZ‐ positive primordium of the prethalamic liminar band in prosomere 3, which borders ventrally the zona incerta, from which it was not distinguished by classic neuroanatomists (PSPa, RLi; Figure 4a–c).…”

“…As regards the entopeduncular nucleus of rodents, Gilbert (1935), Papez (1940), Keyser (1972, 1979) and Marchand et al (1986) agreed that it originates in a preincertal hypothalamic area (just rostral to the prethalamic zona incerta in the prosomeric model), where it is found also in adult rodents. The described preincertal origin of the rodent entopeduncular nucleus corresponds within the prosomeric model to an origin in the alar subparaventricular area of the peduncular hypothalamus (Diaz et al, 2023; Puelles & Rubenstein, 2003, 2015; Puelles et al, 2012, 2021).…”