Table 1.
Anatomical connections between Locus Coeruleus and hypothalamus which have been documented by experimental/post-mortem studies
| Study | Animal | Method | Hypothalamus | Preoptic | Supraoptic | Median | Mammillary | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Ant | Post | Med | Lat | MPO | LPO | PeVN | SCN | PVN | AN | LHN | SON | DMN | VMN | ArN | PN | TMN | |||
| Mizuno, 1970 | Rabbits | Electrolytic lesion of hypothalamus and EM observation of cellular debris | AFF | AFF | AFF | AFF | |||||||||||||
| Mizuno, 1972 | Rabbits | Electrolytic lesion of hypothalamus and EM observation of cellular debris | AFF | AFF | |||||||||||||||
| Ross, 1974 | Rats | Electrolytic lesion of LC and DBH staining | EFF | ||||||||||||||||
| Kobayashi, 1974 | Rats | Electrolytic lesion of LC and NA concentration assay | EFF | EFF | |||||||||||||||
| Roizen, 1976 | Rats | Stereotaxic lesion of dorsal NA bundle and NA concentration assay | EFF | ||||||||||||||||
| McBride, 1976 | Cats | Electrolytic lesion of LC and FH staining | EFF | EFF | |||||||||||||||
| 6-OHDA lesion of LC and FH staining | EFF | ||||||||||||||||||
| Injection of radiolabeled proline in the LC | EFF | ||||||||||||||||||
| HRP (retrograde tracing) | EFF | EFF | |||||||||||||||||
| Worth, 1976 | Rats | 6-OHDA lesion of LC and NA concentration assay | EFF | EFF | EFF | EFF | |||||||||||||
| Swanson, 1976 | Rats | Injection of radiolabeled proline in the MPO | AFF | ||||||||||||||||
| Saper, 1976 | Rats | Injection of radiolabeled proline in the VMN | AFF | ||||||||||||||||
| Farley, 1977 | Humans | NA concentration assay in post-mortem brain sample | EFF | EFF | EFF | EFF | EFF | ||||||||||||
| Jones, 1977 | Rats | NA concentration assay; injection of radiolabeled proline | EFF | EFF | EFF | EFF | |||||||||||||
| Levin, 1977 | Rats | Injection of 3H-fucosyl-glycoprotein in the LC | EFF | EFF | |||||||||||||||
| Jones, 1977 | Rats | Injection of radiolabeled amino acid | EFF | EFF | EFF | EFF | |||||||||||||
| Cedarbaum, 1978 | Rats | HRP into hypothalamus | AFF | AFF | AFF | AFF | AFF | AFF | |||||||||||
| Levin, 1978 | Rats | Injection of radiolabeled leucine in the LC | EFF | EFF | |||||||||||||||
| Bowden, 1978 | Rhesus monkeys | Injection of radiolabeled proline in the LC | EFF | EFF | EFF | EFF | |||||||||||||
| Cimarusti, 1979 | Rats | DBH staining of hypothalamus | EFF | EFF | EFF | ||||||||||||||
| Saper, 1979 | Rats | Injection of radiolabeled proline in the lateral hypothalamic nucleus | AFF | ||||||||||||||||
| Clavier, 1979 | Rats | Injection of HRP in the LC | AFF | AFF | |||||||||||||||
| Mason, 1979 | Rats | Injection of HRP in the hypothalamus | EFF | EFF | EFF | EFF | |||||||||||||
| Iijima, 1980 | Rats | Injection of HRP in the SON | EFF | ||||||||||||||||
| Palkovits, 1980 | Rats | Lesion of NA nuclei (not only LC) and NA concentration assay | EFF | EFF | EFF | EFF | |||||||||||||
| Anterograde tracing with CBT or PHLA in hypothalamus | AFF | AFF | AFF | AFF | |||||||||||||||
| Barone, 1981 | Rats | Injection of HRP in the lateral hypothalamus | EFF | ||||||||||||||||
| McKellar, 1981 | Rats | Injection of radiolabeled amino acid in the LC | EFF | ||||||||||||||||
| Sawchenko, 1981 | Rats | Both injection of radiolabeled amino acid in the LC and retrograde tracing with TB | EFF | EFF | |||||||||||||||
| Kita, 1982 | Rats | Injection of HRP in the lateral hypothalamus | EFF | ||||||||||||||||
| Veazey, 1982 | Monkeys | Injection of radiolabeled amino acid in the posterior hypothalamus | AFF | AFF | |||||||||||||||
| Hawthorn, 1985 | Rats | Electric stereotaxic lesion of paraventricular, supraoptic and suprachiasmatic nuclei and VPA concentration assessment | AFF | AFF | AFF | ||||||||||||||
| Tribollet, 1985 | Rats | Injection of HRP in the supraoptic nucleus | EFF | ||||||||||||||||
| Injection of TB in the supraoptic nucleus | EFF | ||||||||||||||||||
| Logue, 1985 | Rats | Intraperitoneal DSP4 administration and NA concentration assessment | EFF | EFF | EFF | EFF | |||||||||||||
| Jones, 1985 | Rats | Injection of radiolabeled leucine in the LC | EFF | EFF | EFF | EFF | |||||||||||||
| Javitch, 1985 | Rats | Mazindol autoradiography via desipramine inhibition of NET | EFF | EFF | EFF | EFF | |||||||||||||
| Sawchenko, 1985 | Rats | Retrograde tracing with TB and immunoreactivity for DBH and NPY | EFF | ||||||||||||||||
| Alonso, 1986 | Rats | Injection of radiolabeled leucine in the SON | AFF | ||||||||||||||||
| Loughlin, 1986 | Rats | Injection of HRP in the hypothalamus | EFF | EFF | EFF | EFF | |||||||||||||
| Loughlin, 1986 (b) | Rats | Injection of HRP in the hypothalamus | EFF | EFF | EFF | EFF | |||||||||||||
| Shirokawa, 1987 | Rats | Electrode stimulation of LC and antidromic assessment of DMN | AFF | ||||||||||||||||
| Rizvi, 1994 | Rats | Anterograde tracing with PHLA/WGA-HRP | AFF | ||||||||||||||||
| Retrograde tracing with FG/WGA-HRP | AFF | ||||||||||||||||||
| Canteras, 1994 | Rats | Injection of HRP in the DMN | AFF | AFF | |||||||||||||||
| Zardetto-Smith, 1995 | Rats | Injection of PHAL in MPO and DBH staining | AFF | ||||||||||||||||
| Luppi, 1995 | Rats | Injection of CTB in the LC | AFF | AFF | AFF | AFF | AFF | AFF | AFF | ||||||||||
| Peyron, 1998 | Rats | Immunohistochemical assay of ORX fibers | AFF (ORX) | AFF (ORX) | AFF (ORX) | AFF (ORX) | |||||||||||||
| Horvath, 1999 | Rats | Immunohistochemical assay of ORX fibers | AFF (ORX) | AFF (ORX) | AFF (ORX) | AFF (ORX) | |||||||||||||
| Monkeys | Immunohistochemical assay of ORX fibers | AFF (ORX) | AFF (ORX) | ||||||||||||||||
| Steininger, 2001 | Rats | Injection of BD into the ventral hypothalamus | AFF | AFF | |||||||||||||||
| Aston-Jones, 2001 | Rats | Transfection with Pseudorabies virus of LC | AFF | AFF | |||||||||||||||
| Krout, 2002 | Rats | Injection of CTB and Pseudorabies virus in the SCN | AFF | ||||||||||||||||
| Chou, 2002 | Rats | Injection of CTB in the preoptic area of hypothalamus | EFF | ||||||||||||||||
| Injection of BD, PHAL, WGA-HRP in the preoptic area | AFF | ||||||||||||||||||
| Baldo, 2003 | Rats | Immunohistochemical assay for DBH | EFF | EFF | EFF | ||||||||||||||
| Injection of BD and PHAL into the LC | EFF | ||||||||||||||||||
| Deurveilher, 2005 | Rats | Injection of CTB and BD into the MPO, DMN and PVN | AFF | AFF | |||||||||||||||
| Lee, 2005 | Rats | Injection of FG and WGA into the LC | AFF | AFF | AFF | AFF | AFF | ||||||||||||
| Espana, 2005 | Rats | Injection of WGA into the LC | AFF (ORX) | ||||||||||||||||
| Reyes, 2005 | Rats | Injection of BD and PHAL into the PVN | AFF | ||||||||||||||||
| Campbell, 2007 | Rats | Transfection of viral vector into the GnRH releasing neurons of preoptic area of hypothalamus | EFF | ||||||||||||||||
| Uschakov, 2007 | Rats | Injection of BD into the MPO | AFF | ||||||||||||||||
| Injection of FG into the LC | AFF | ||||||||||||||||||
| Puskas, 2010 | Rats | Immunohistochemical assay of ORX fibers | AFF (ORX) | AFF (ORX) | |||||||||||||||
| Geerling, 2010 | Rats | Injection of PHAL into the PVN | AFF | ||||||||||||||||
| Sobrinho, 2011 | Rats | Injection of FG into the median/mammillary area of hypothalamus | EFF | EFF | EFF | ||||||||||||||
| Dimitrov, 2013 | Mice | Injection of FG into the LC | AFF | AFF | AFF (GABA) | AFF | AFF (GABA) | ||||||||||||
| Injection of BD into hypothalamus | AFF | AFF | AFF (GABA) | AFF (GABA) | |||||||||||||||
| Yoon, 2013 | Rats | Injection of green RetroBeads™ into the LC | AFF (NPY) | ||||||||||||||||
The table reports all the available studies performed in animals or in humans assessing the anatomical connections between Locus Coeruleus and the hypothalamus; first author, year of publication, animal model and tracing technique are reported in the first three columns on the left. In the following columns, observed connections are enlisted under the generic label of “hypothalamus” or under the specific labels of hypothalamic area/nucleus explored, according to reported results. When specified in the study, the neurotransmitter released by hypothalamic projections is reported
AFF afferences from hypothalamus or hypothalamic nuclei to the LC, Ant anterior hypothalamus, AN anterior nucleus, ArN arcuate nucleus, BD biotinylated dextran, CTB cholera toxin B, DBH dopamine beta-hydroxylase, DMN dorsomedial nucleus, DSP-4 N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine, EFF efferences from the LC to hypothalamus or hypothalamic nuclei, EM electronic microscopy, FH fink-heimer, FG fluorogold, GABA gamma-amino-butyric-acid, GnRH gonadotropin release-hormone, HRP horseradish peroxidase, Lat lateral hypothalamus, LC Locus Coeruleus, LHN lateral hypothalamic nucleus, LPO lateral preoptic nucleus, Med medial hypothalamus, MPO medial preoptic nucleus, NA noradrenaline, NPY neuropeptide-Y, 6-OHDA 6-hydroxydopamine, ORX orexin, PeVN periventricular nucleus, PHAL phaseolus vulgaris leukoagglutinin, PN posterior nucleus, Post posterior hypothalamus, PVN paraventricular nucleus, SCN suprachiasmatic nucleus, SON supraoptic nucleus, TB true blue, TMN tuberomammillary nucleus, VMN ventromedial nucleus, VPA vasopressin, WGA wheat germ agglutinin