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The Lateral Hypothalamus Is Involved in the Pathway Mediating the Hypotensive Response to Cingulate Cortex-Cholinergic Stimulation

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Abstract

1. The injection of acetylcholine (ACh) into the medial prefrontal cortex (MPFC) caused marked hypotensive response in either unanesthetized or anesthetized rats.

2. The present experiment was designed to investigate anatomical connections of the ACh injection site in the MPFC with putative autonomic-related brain nuclei, as well as their possible involvement in the mediation of the hypotensive response to ACh.

3. For the above purpose, the bidirectional neuronal tracer biotinylated dextran amine (BDA) was injected into Cg1 and Cg3 areas, within the MPFC of male Wistar rats. Five days later the animals were sacrificed and brain slices were processed and analyzed to determine neuronal projections efferent from as well afferent to the MPFC.

4. Neuronal staining was more prominent in regions ipsilateral to the BDA injection site. Prominent efferent projections of the MPFC were observed in the contralateral MPFC; ipsi- and contralateral amygdala and hypothalamus; ipsilateral septal area, diagonal band, and zona incerta.

5. Similar but not equal patterns of neuronal labeling were observed when BDA injections were performed within the two adjacent MPFC areas. BDA injections centered in the ACh injection site in the Cg3 area caused strong labeling in the septal area and diagonal band as well as an overall hypothalamic labeling. Within the hypothalamus an intense cortical projection was observed in the lateral hypothalamus (LH). BDA injections into the Cg1 area caused a more evident labeling of the amygdaloid complex.

6. Neuronal cell bodies were evident throughout the MPFC as well as in the sensory-motor cortex when BDA was injected into the LH, thus indicating a massive ipsilateral cortical projection from the Cg3 to the LH.

7. Bilateral NMDA-induced lesions within the LH caused a significant attenuation of the depressor responses to ACh injection in the MPFC, whereas unilateral lesions were marginally effective. These results indicate the involvement of the LH in the mediation of the hypotensive response to ACh injection into the MPFC as well as the bilateral distribution of the hypotensive pathway.

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REFERENCES

  • Allen, G. V., and Cechetto, D. F. (1992). Functional and anatomical organization of cardiovascular pressor and depressor sites in the lateral hypothalamic area: I. Descending projections. J. Comp. Neurol. 315:313-332.

    Google Scholar 

  • Allen, G. V., and Cechetto, D. F. (1993). Functional and anatomical organization of cardiovascular pressor and depressor sites in the lateral hypothalamic area. II. Ascending projections. J. Comp. Neurol. 330:421-438.

    Google Scholar 

  • Bacon, S. J., and Smith, A. D. (1993). A monosynaptic pathway from an identified vasomotor centre in the medial prefrontal cortex to an autonomic area in the thoracic spinal cord. Neuroscience 54:719-728.

    Google Scholar 

  • Barbas, H., and Pandya, D. N. (1991). Patterns of connections of the prefrontal cortex in the rhesus monkeys associated with cortical architecture. In Levin, H. S., Eisenberg, H. M., and Benton, A. L. (eds.), Frontal Lobe Function and Dysfunction, Oxford University Press, New York, pp. 35-58.

    Google Scholar 

  • Burns, S. M., and Wyss, J. M. (1985). The involvement of the anterior cingulate cortex in blood pressure control. Brain Res. 340:71-77.

    Google Scholar 

  • Cechetto, D. F., and Chen, S. J. (1990). Subcortical sites mediating sympathetic responses from insular cortex in rats. Am. J. Physiol. 258:R245-R255.

    Google Scholar 

  • Crippa, G. E., Lewis, S. J., Johnson, A. K., and Corrêa F. M. A. (2000). Medial prefrontal cortex acetylcholine injection-induced hypotension: The role of hindlimb vasodilation. J. Auton. Nerv. System 79:1-7.

    Google Scholar 

  • Crippa, G. E., Peres-Polon, V. L., Kuboyama, R. H., and Corrêa, F. M. A. (1999). Cardiovascular response to the injection of acetylcholine into the anterior cingulate region of the medial prefrontal cortex of unanesthetized rats. Cereb. Cortex 9:362-365.

    Google Scholar 

  • Delgado, J. M. R. (1960). Circulatory effects of cortical stimulation. Physiol. Rev. 40(Suppl.4):146-171.

    Google Scholar 

  • Eckenstein, F., and Thoenen, H. (1983). Cholinergic neurons in the rat cerebral cortex demonstrated by immunohistochemical localization of choline acetyltransferase. Neurosci. Lett. 36:211-215.

    Google Scholar 

  • Fibiger, H. C. (1982). The organization and some projections of cholinergic neurons of the mammalian forebrain. Brain Res. Rev. 4:372-388.

    Google Scholar 

  • Fisk, G. D., and Wyss, J. M. (1997). Pressor and depressor sites are intermingled in the cingulate cortex of the rat. Brain Res. 754:204-212.

    Google Scholar 

  • Frysztak, R. J., and Neafsey, E. J. (1994). The effect of medial frontal cortex lesions on cardiovascular conditioned emotional responses in the rat. Brain Res. 643:181-193.

    Google Scholar 

  • Goldman-Rakic, P. S. (1987). Circuitry of primate prefrontal cortex and the regulation of behavior by representational memory. In Mountcastle, V. B., Plum, F., and Geiger, S. R. (eds.), Handbook of physiology: Vol. 5. The Nervous System, American Physiological Society, Bethesda, pp. 373-417.

    Google Scholar 

  • Hardy, S. G. P., and Holmes, D. E. (1988). Prefrontal stimulus-produced hypotension in rat. Exp. Brain Res. 73:249-255.

    Google Scholar 

  • Hardy, S. G. P., and Mack, S. M. (1990). Brainstem mediation of prefrontal stimulus-produced hypotension. Exp. Brain Res. 79:393-399.

    Google Scholar 

  • Houser, C. R., Crawford, G. D., Barber R. P., Salvaterra, P. M., and Vaughn, J. E., (1983). Organization and morphological characteristics of cholinergic neurons: An immunocytochemical study with a monoclonal antibody to choline acetyltransferase. Brain Res. 266:97-119.

    Google Scholar 

  • Houser, C. R., Crawford, G. D., Salvaterra, P. M., and Vaughn, J. E. (1985). Immunocytochemical localization of choline acetyltransferase in rat cerebral cortex: A study of cholinergic neurons and synapses. J. Comp. Neurol. 234:17-34.

    Google Scholar 

  • Hurley-Gius, K. M., and Neafsey, E. J. (1986). The medial frontal cortex and gastric motility: Microstimulation results and their possible significance for the overall pattern of organization of rat frontal and parietal cortex. Brain Res. 365:241-248.

    Google Scholar 

  • Iwata, J., LeDoux, J. E., Meeley, M. P., Arneric, S., and Reis, D. J. (1986a). Intrinsic neurons in the amygdaloid field projected to by the medial geniculate body mediate emotional responses conditioned to acoustic stimuli. Brain Res. 383:195-214.

    Google Scholar 

  • Iwata, J., leDoux, J.E., and Reis D.J. (1986b). Destruction of intrinsic neurons in the lateral hypothalamus disrupts the classical conditioning of autonomic but not behavioral emotional responses in the rat. Brain Res. 368:161-166.

    Google Scholar 

  • Kaada, B. R. (1960). Cingulate, posterior orbital, anterior insular and temporal pole cortex. In: Field., J., Magoun, H. W., and Hall, V. E. (eds.), Handbook of Physiology: Neurophysiology. American Physiological Society, Washington, pp. 1345-1372.

    Google Scholar 

  • Krettek, J. E., and Price, J. L. (1977). The cortical projections of the mediodorsal nucleus and adjacent thalamic nuclei in the rat. J. Comp. Neurol. 171:157-192.

    Google Scholar 

  • Leonard, C. M. (1969). The prefrontal cortex of the rat. I. Cortical projection of the mediodorsal nucleus. II. Efferent connections. Brain Res. 12:321-343.

    Google Scholar 

  • Papez, J. W. (1937). A proposed mechanism of emotion. Arch. Neurol. Psychiat. 38:725-743.

    Google Scholar 

  • Paxinos, G., and Watson, C. (1986). The Rat Brain in Stereotaxic Coordinates, 2nd ed., Academic Press, Sydney.

    Google Scholar 

  • Preuss, T. M., and Goldman-Rakic, P. S. (1991a). Myelo-and cytoarchitecture of the granular frontal cortex and surrounding regions in the strepsirhine primate Galago and the anthropoid primate Macaca. J. Comp. Neurol. 310:429-474.

    Google Scholar 

  • Preuss, T. M., and Goldman-Rakic, P. S. (1991b). Ipsilateral cortical connections of granular frontal cortex in the strepsirhine primate Galago, with comparative comments on anthropoid primates. J. Comp. Neurol. 310:507-549.

    Google Scholar 

  • Reis, D. J., and LeDoux, J. E. (1987). Some central neural mechanisms governing resting and behaviorally coupled control of blood pressure. Circulation 76(Suppl. I):12-19.

    Google Scholar 

  • Rose, J. E., and Woolsey, C. N. (1948). The orbitofrontal cortex and its connections with the mediodorsal nucleus in rabbit, sheep and cat. Res. Publ. Ass. Nerv. Ment. Dis. 27:210-232.

    Google Scholar 

  • Spencer, S. E., Sawyer, W. B., and Loewy, A. D. (1988). L-Glutamate stimulation of the zona incerta in the rat decreases heart rate and blood pressure. Brain Res. 458:72-81.

    Google Scholar 

  • Spencer, S. E., Sawyer, W. B., and Loewy, A. D. (1989). Cardiovascular effects produced by L-glutamate stimulation of the lateral hypothalamic area. Am. J. Physiol. 257:H540-H552.

    Google Scholar 

  • Terreberry, R., and Neafsey, E. J. (1983). Rat medial frontal cortex: A visceral motor region with a direct projection to the solitary nucleus. Brain Res. 278:245-249.

    Google Scholar 

  • Verberne, A. J. M. (1996). Medullary sympathoexcitatory neurons are inhibited by activation of the medial prefrontal cortex in the rat. Am. J. Physiol. 270:R713-R719.

    Google Scholar 

  • Verberne, A. J. M., and Owens, N. C. (1998). Cortical modulation of the cardiovascular system. Prog. Neurobiol. 54:149-168.

    Google Scholar 

  • Winn, P., Clark, A., Hastings, M., Clark, J., Latimer, M., Rugg, E., and Brownlee, B. (1990). Excitotoxic lesions of the lateral hypothalamus made by N-methyl-d-aspartate in the rat: Behavioural, histological and biochemical analyses. Exp. Brain Res. 82:628-636.

    Google Scholar 

  • Yasui, Y., Breder, C. D., Saper, C. B., and Cechetto, D. F. (1991). Autonomic responses and efferent pathways from the insular cortex in the rat. J. Comp. Neurol. 303:355-374.

    Google Scholar 

  • Zilles, K., and Wree, A. (1985). Cortex: Areal and laminar structure. In Paxinos, G. (ed.), The Rat Nervous System, Vol. 1, Academic Press, Sidney, pp. 375-415.

    Google Scholar 

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Pajolla, G.P., Crippa, G.E., Corrêa, S.A.L. et al. The Lateral Hypothalamus Is Involved in the Pathway Mediating the Hypotensive Response to Cingulate Cortex-Cholinergic Stimulation. Cell Mol Neurobiol 21, 341–356 (2001). https://doi.org/10.1023/A:1012650021137

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