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The Journal of Physiological Sciences

, Volume 68, Issue 4, pp 415–423 | Cite as

Effect of basal forebrain stimulation on extracellular acetylcholine release and blood flow in the olfactory bulb

  • Sae UchidaEmail author
  • Fusako Kagitani
Original Paper

Abstract

The olfactory bulb receives cholinergic basal forebrain input, as does the neocortex; however, the in vivo physiological functions regarding the release of extracellular acetylcholine and regulation of regional blood flow in the olfactory bulb are unclear. We used in vivo microdialysis to measure the extracellular acetylcholine levels in the olfactory bulb of urethane-anesthetized rats. Focal chemical stimulation by microinjection of l-glutamate into the horizontal limb of the diagonal band of Broca (HDB) in the basal forebrain, which is the main source of cholinergic input to the olfactory bulb, increased extracellular acetylcholine release in the ipsilateral olfactory bulb. When the regional cerebral blood flow was measured using laser speckle contrast imaging, the focal chemical stimulation of the HDB did not significantly alter the blood flow in the olfactory bulb, while increases were observed in the neocortex. Our results suggest a functional difference between the olfactory bulb and neocortex regarding cerebral blood flow regulation through the release of acetylcholine by cholinergic basal forebrain input.

Keywords

Cholinergic system Horizontal limb of the diagonal band of Broca Laser speckle contrast imaging Microdialysis Rat 

Notes

Acknowledgements

This work was supported by JSPS KAKENHI (Grant Number JP15K08225 to S.U.) and by the Smoking Research Foundation.

Author contributions

Both authors contributed to the conception and design of the research, performed experiments and analyzed data, and interpreted the results of the experiments. S.U. drafted the manuscript; both authors edited and revised the manuscript, and approved the final manuscript.

Compliance with ethical standards

Conflict of interest

The authors have no conflicts of interest to declare.

References

  1. 1.
    Devanand DP, Liu X, Tabert MH, Pradhaban G, Cuasay K, Bell K, de Leon MJ, Doty RL, Stern Y, Pelton GH (2008) Combining early markers strongly predicts conversion from mild cognitive impairment to Alzheimer’s disease. Biol Psychiatry 64:871–879CrossRefGoogle Scholar
  2. 2.
    Djordjevic J, Jones-Gotman M, De Sousa K, Chertkow H (2008) Olfaction in patients with mild cognitive impairment and Alzheimer’s disease. Neurobiol Aging 29:693–706CrossRefGoogle Scholar
  3. 3.
    Doty RL, Kamath V (2014) The influences of age on olfaction: a review. Front Psychol. doi: 10.3389/fpsyg.2014.00020 CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Ballinger EC, Ananth M, Talmage DA, Role LW (2016) Basal forebrain cholinergic circuits and signaling in cognition and cognitive decline. Neuron 91:1199–1218CrossRefGoogle Scholar
  5. 5.
    D’Souza RD, Vijayaraghavan S (2014) Paying attention to smell: cholinergic signaling in the olfactory bulb. Front Synaptic Neurosci. doi: 10.3389/fnsyn.2014.00021 CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Micheau J, Marighetto A (2011) Acetylcholine and memory: a long, complex and chaotic but still living relationship. Behav Brain Res 221:424–429CrossRefGoogle Scholar
  7. 7.
    Biesold D, Inanami O, Sato A, Sato Y (1989) Stimulation of the nucleus basalis of Meynert increases cerebral cortical blood flow in rats. Neurosci Lett 98:39–44CrossRefGoogle Scholar
  8. 8.
    Cao W-H, Inanami O, Sato A, Sato Y (1989) Stimulation of the septal complex increases local cerebral blood flow in the hippocampus in anesthetized rats. Neurosci Lett 107:135–140CrossRefGoogle Scholar
  9. 9.
    Kurosawa M, Sato A, Sato Y (1989) Stimulation of the nucleus basalis of Meynert increases acetylcholine release in the cerebral cortex in rats. Neurosci Lett 98:45–50CrossRefGoogle Scholar
  10. 10.
    Sato A, Sato Y (1992) Regulation of regional cerebral blood flow by cholinergic fibers originating in the basal forebrain. Neurosci Res 14:242–274CrossRefGoogle Scholar
  11. 11.
    Uchida S, Hotta H, Misawa H, Kawashima K (2011) Sustained subcutaneous infusion of nicotine enhances cholinergic vasodilation in the cerebral cortex induced by stimulation of the nucleus basalis of Meynert in rats. Eur J Pharmacol 654:235–240CrossRefGoogle Scholar
  12. 12.
    Rye DB, Wainer BH, Mesulam MM, Mufson EJ, Saper CB (1984) Cortical projections arising from the basal forebrain: a study of cholinergic and noncholinergic components employing combined retrograde tracing and immunohistochemical localization of choline acetyltransferase. Neuroscience 13:627–643CrossRefGoogle Scholar
  13. 13.
    Wenk H, Bigl V, Meyer U (1980) Cholinergic projections from magnocellular nuclei of the basal forebrain to cortical areas in rats. Brain Res 2:295–316CrossRefGoogle Scholar
  14. 14.
    Adachi T, Inanami O, Ohno K, Sato A (1990) Responses of regional cerebral blood flow following focal electrical stimulation of the nucleus basalis of Meynert and the medial septum using the [14C]iodoantipyrine method in rats. Neurosci Lett 112:263–268CrossRefGoogle Scholar
  15. 15.
    Milner TA, Amaral DG (1984) Evidence for a ventral septal projection to the hippocampal formation of the rat. Exp Brain Res 55:579–585CrossRefGoogle Scholar
  16. 16.
    Záborszky L, Carlsen J, Brashear HR, Heimer L (1986) Cholinergic and GABAergic afferents to the olfactory bulb in the rat with special emphasis on the projection neurons in the nucleus of the horizontal limb of the diagonal band. J Comp Neurol 243:488–509CrossRefGoogle Scholar
  17. 17.
    Whitehouse PJ, Price DL, Struble RG, Clark AW, Coyle JT, DeLong MR (1982) Alzheimer’s disease and senile dementia: loss of neurons in the basal forebrain. Science 215:1237–1239CrossRefGoogle Scholar
  18. 18.
    Grothe M, Heinsen H, Teipel S (2013) Longitudinal measures of cholinergic forebrain atrophy in the transition from healthy aging to Alzheimer’s disease. Neurobiol Aging 34:1210–1220CrossRefGoogle Scholar
  19. 19.
    McGeer PL, McGeer EG, Suzuki J, Dolman CE, Nagai T (1984) Aging, Alzheimer’s disease, and the cholinergic system of the basal forebrain. Neurology 34:741–745CrossRefGoogle Scholar
  20. 20.
    Uchida S, Suzuki A, Kagitani F, Hotta H (2006) Responses of acetylcholine release and regional blood flow in the hippocampus during walking in aged rats. J Physiol Sci 56:253–257CrossRefGoogle Scholar
  21. 21.
    Shiba K, Machida T, Uchida S, Hotta H (2006) Effects of nicotine on regional blood flow in the olfactory bulb in rats. Eur J Pharmacol 546:148–151CrossRefGoogle Scholar
  22. 22.
    Shiba K, Machida T, Uchida S, Hotta H (2009) Sympathetic neural regulation of olfactory bulb blood flow in adult and aged rats. Auton Neurosci 147:75–79CrossRefGoogle Scholar
  23. 23.
    Dunn AK, Bolay H, Moskowitz MA, Boas DA (2001) Dynamic imaging of cerebral blood flow using laser speckle. J Cereb Blood Flow Metab 21:195–201CrossRefGoogle Scholar
  24. 24.
    Piché M, Uchida S, Hara S, Aikawa Y, Hotta H (2010) Modulation of somatosensory-evoked cortical blood flow changes by GABAergic inhibition of the nucleus basalis of Meynert in urethane-anaesthetized rats. J Physiol 588:2163–2171CrossRefGoogle Scholar
  25. 25.
    Hotta H, Uchida S, Kagitani F, Maruyama N (2011) Control of cerebral cortical blood flow by stimulation of basal forebrain cholinergic areas in mice. J Physiol Sci 61:201–209CrossRefGoogle Scholar
  26. 26.
    Uchida S, Hotta H, Misawa H, Kawashima K (2013) The missing link between long-term stimulation of nicotinic receptors and the increases of acetylcholine release and vasodilation in the cerebral cortex of aged rats. J Physiol Sci 63:95–101CrossRefGoogle Scholar
  27. 27.
    Paxinos G, Watson C (2009) The rat brain in stereotaxic coordinates. Compact 6th edition. Academic Press, AmsterdamGoogle Scholar
  28. 28.
    El-Etri MM, Ennis M, Griff ER, Shipley MT (1999) Evidence for cholinergic regulation of basal norepinephrine release in the rat olfactory bulb. Neuroscience 93:611–617CrossRefGoogle Scholar
  29. 29.
    Zilles K (1985) The cortex of the rat. Springer, BerlinCrossRefGoogle Scholar
  30. 30.
    Mesulam MM, Mufson EJ, Wainer BH, Levey AI (1983) Central cholinergic pathways in the rat: an overview based on an alternative nomenclature (Ch1-Ch6). Neuroscience 10:1185–1201CrossRefGoogle Scholar
  31. 31.
    Sato A, Sato Y, Uchida S (2004) Activation of the intracerebral cholinergic nerve fibers originating in the basal forebrain increases regional cerebral blood flow in the rat’s cortex and hippocampus. Neurosci Lett 361:90–93CrossRefGoogle Scholar
  32. 32.
    Luiten PG, Gaykema RP, Traber J, Spencer DG Jr (1987) Cortical projection patterns of magnocellular basal nucleus subdivisions as revealed by anterogradely transported Phaseolus vulgaris leucoagglutinin. Brain Res 413:229–250CrossRefGoogle Scholar
  33. 33.
    Kagitani F, Uchida S, Hotta H, Sato A (2000) Effects of nicotine on blood flow and delayed neuronal death following intermittent transient ischemia in rat hippocampus. Jpn J Physiol 50:585–595CrossRefGoogle Scholar
  34. 34.
    Uchida S, Kagitani F, Nakayama H, Sato A (1997) Effect of stimulation of nicotinic cholinergic receptors on cortical cerebral blood flow and changes in the effect during aging in anesthetized rats. Neurosci Lett 228:203–206CrossRefGoogle Scholar
  35. 35.
    Uchida S, Hotta H, Kawashima K (2009) Long-term nicotine treatment reduces cerebral cortical vasodilation mediated by alpha4beta2-like nicotinic acetylcholine receptors in rats. Eur J Pharmacol 609:100–104CrossRefGoogle Scholar
  36. 36.
    Durand M, Coronas V, Jourdan F, Quirion R (1998) Developmental and aging aspects of the cholinergic innervation of the olfactory bulb. Int J Dev Neurosci 16:777–785CrossRefGoogle Scholar
  37. 37.
    Gotti C, Zoli M, Clementi F (2006) Brain nicotinic acetylcholine receptors: native subtypes and their relevance. Trends Pharmacol Sci 27:482–491CrossRefGoogle Scholar
  38. 38.
    Wada E, Wada K, Boulter J, Deneris E, Heinemann S, Patrick J, Swanson LW (1989) Distribution of alpha 2, alpha 3, alpha 4, and beta 2 neuronal nicotinic receptor subunit mRNAs in the central nervous system: a hybridization histochemical study in the rat. J Comp Neurol 284:314–335CrossRefGoogle Scholar
  39. 39.
    Vaucher E, Hamel E (1995) Cholinergic basal forebrain neurons project to cortical microvessels in the rat: electron microscopic study with anterogradely transported Phaseolus vulgaris leucoagglutinin and choline acetyltransferase immunocytochemistry. J Neurosci 15:7427–7441CrossRefGoogle Scholar
  40. 40.
    Vaucher E, Borredon J, Bonvento G, Seylaz J, Lacombe P (1997) Autoradiographic evidence for flow-metabolism uncoupling during stimulation of the nucleus basalis of Meynert in the conscious rat. J Cereb Blood Flow Metab 17:686–694CrossRefGoogle Scholar
  41. 41.
    Devore S, Linster C (2012) Noradrenergic and cholinergic modulation of olfactory bulb sensory processing. Front Behav Neurosci. doi: 10.3389/fnbeh.2012.00052 CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Yousem DM, Geckle RJ, Bilker WB, Doty RL (1998) Olfactory bulb and tract and temporal lobe volumes. Normative data across decades. Ann N Y Acad Sci 855:546–555CrossRefGoogle Scholar
  43. 43.
    Hinds JW, McNelly NA (1977) Aging of the rat olfactory bulb: growth and atrophy of constituent layers and changes in size and number of mitral cells. J Comp Neurol 72:345–367CrossRefGoogle Scholar
  44. 44.
    Kraemer S, Apfelbach R (2004) Olfactory sensitivity, learning and cognition in young adult and aged male Wistar rats. Physiol Behav 81:435–442CrossRefGoogle Scholar
  45. 45.
    Ogoh S (2017) Relationship between cognitive function and regulation of cerebral blood flow. J Physiol Sci 67:345–351CrossRefGoogle Scholar
  46. 46.
    Ushijima Y, Okuyama C, Mori S, Nakamura T, Kubota T, Nishimura T (2002) Relationship between cognitive function and regional cerebral blood flow in Alzheimer’s disease. Nucl Med Commun 23:779–784CrossRefGoogle Scholar

Copyright information

© The Physiological Society of Japan and Springer Japan 2017

Authors and Affiliations

  1. 1.Department of Autonomic NeuroscienceTokyo Metropolitan Institute of GerontologyTokyoJapan

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