Skip to main content
SpringerLink
Log in

Neurotensin-induced excitation of neurons of the rat's frontal cortex studied intracellularly in vitro

  • Published:
Experimental Brain Research Aims and scope Submit manuscript

Summary

The actions of neurotensin (NT) on frontal pyramidal neurons were studied in vitro in slices of rat cerebral cortex using current clamp and single electrode voltage clamp (SEVC) techniques. Bath application of NT (0.1 μM–10 μM) induced a depolarization (2–13 mV) in 88% of the pyramidal cells, this effect was associated with a decrease in input conductance of 5–35% and its reversal potential was estimated at -88 +/-9.7mV. Typically, this depolarizing effect of NT was transient, since no cell responded to a second application of the peptide within 20 min after the first one. NT also induced an increase in the rate of firing of pyramidal cells evoked by direct stimulation, even when an hyperpolarizing current was applied to prevent the depolarization induced by NT. This effect could neither be explained by a decrease of the post-spike after-hyperpolarization, nor by an increase of the persistent sodium current which sustains the spiking of pyramidal cells, since the former was not affected consistently by NT and the later was insensitive to the peptide. This excitation of pyramidal neurons by NT persisted after blockade of synaptic transmission. On the other hand, NT also enhanced the synaptic noise recorded in pyramidal cells in standard perfusing medium. Furthermore, dopaminergic antagonists and noradrenergic antagonists failed to block these effects of NT. Finally, the inactive fragment of the peptide, NT(1–8), did not affect membrane properties of pyramidal cells. All together, these results suggest that NT excites frontal cortical neurons through the activation of specific NT receptors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Adams RP, Brown DA, Constanti A (1982) Pharmacological inhibition of the M-current. J Physiol (Lond) 322: 223–262

    Google Scholar 

  • Alger BE, Nicoll RA (1980) Spontaneous inhibitory postsynaptic potentials in hippocampus: mechanism for tonic inhibition. Brain Res 200: 195–200

    Google Scholar 

  • Andrade R, Aghajanian GK (1981) Neurotensin selectively activates dopaminergic neurons of the substantia nigra. Soc Neurosci Abstr 7: 573

    Google Scholar 

  • Baldino Jr F, Wolfson B (1985) Postsynaptic actions of neurotensin on preoptic-anterior hypothalamic neurons in vitro. Brain Res 325: 161–170

    Google Scholar 

  • Behbehani MM, Shipley M, McLean JH (1987) Effect of neurotensin on neurons in the periaqueductal gray: an in vitro study. J Neurosci 7: 2035–2040

    Google Scholar 

  • Carraway RE, Leeman SE (1973) The isolation of a new hypotensive peptide, neurotensin, from bovine hypothalami. J Biol Chem 248: 6854–6861

    Google Scholar 

  • Carraway RE, Leeman SE (1976) Characterization of radioimmunoassayable neurotensin in the rat: its differential distribution in the central nervous system, small intestine and stomach. J Biol Chem 251: 7045–7052

    Google Scholar 

  • Crépel F, Pénit-Soria J (1986) Inward rectification and low threshold calcium conductance in rat cerebellar Purkinje cells: an in vitro study. J Physiol (Lond) 372: 1–23

    Google Scholar 

  • Ervin GN, Birkemo LS, Nemeroff CB, Prange AJ Jr (1981) Neurotensin blocks certain amphetamine-induced behaviors. Nature 291: 73–76

    Google Scholar 

  • Fuxe K, Hökfelt T, Johansson G, Lidbrink P, Ljungdahl A (1974) The origin of the dopamine nerve terminals in the limbic and frontal cortex: evidence for meso-cortico dopamine neurons. Brain Res 82: 349–355

    Google Scholar 

  • Galvan M, Adams PR (1982) Control of calcium current in rat sympathetic neurons by norepinephrine. Brain Res 244: 135–144

    Google Scholar 

  • Halliwell JV (1986) M-current in human neocortical neurones. Neurosci Lett 67: 1–6

    Google Scholar 

  • Halliwell JV, Adams PR (1982) Voltage-clamp analysis of muscarinic excitation in hippocampal neurons. Brain Res 250: 71–92

    Google Scholar 

  • Hervé D, Tassin JP, Studler JM, Dana C, Kitabgi P, Vincent JP, Glowinski J, Rostène W (1986) Dopaminergic control of 1-labeled neurotensin binding site density in corticolimbic structures of the rat brain. Proc Natl Acad Sci USA 83: 6203–6207

    Google Scholar 

  • Hökfelt T, Everitt BJ, Theodorsson-Norheim E, Goldstein M (1984) Occurrence of neurotensinlike immunoreactivity in subpopulations of hypothalamic, mesencephalic, and medullary catecholamine neurons. J Comp Neurol 222: 543–559

    Google Scholar 

  • Kalivas PW, Burgess SK, Nemeroff CB, Prange AJ Jr (1983) Behavioral and neurochemical effects of neurotensin microinjections into the ventral tegmental area in the rat. Neurosciences 8: 487–493

    Google Scholar 

  • Kalivas PW (1984) Neurotensin in the ventromedial mesencephalon of the rat: anatomical and functional considerations. J Comp Neurol 226: 495–507

    Google Scholar 

  • Komatsu Y, Nakajima S, Tomaya K, Fetz EE (1988) Intracortical connectivity revealed by spike-triggered averaging in slice preparation of cat visual cortex. Brain Res 442: 359–362

    Google Scholar 

  • Lancaster B, Nicoll RA (1987) Properties of two calcium-activated hyperpolarizations in rat hippocampal neurones. J Physiol (Lond) 389: 187–203

    Google Scholar 

  • Lindvall O, Björklund A, Moore R, Steveni V (1974) Mesencephalic dopamine neurons projecting to the frontal cortex in the rat. Brain Res 81: 325–331

    Google Scholar 

  • McCormick DA, Connors BW, Lighthall JW, Prince DA (1985) Comparative electrophysiology of pyramidal and sparsely spiny stellate neurons of the neocortex. J Neurophysiol 54: 782–806

    Google Scholar 

  • Madison DV, Nicoll RA (1986) Actions of noradrenaline recorded intracellularly in rat hippocampal CA1 pyramidal neurones in vitro. J Physiol (Lond) 372: 221–244

    Google Scholar 

  • Marwaha J, Hoffer B, Freedman R (1980) Electrophysiological actions of neurotensin in rat cerebellum. Regular Peptides 1: 115–125

    Google Scholar 

  • Mayer ML (1985) A calcium-activated chloride current generates the after-depolarization of rat sensory neurones in culture. J Physiol (Lond) 364: 217–230

    Google Scholar 

  • Miletic V, Randic M (1979) Neurotensin excites cat spinal neurones located in laminae I–III. Brain Res 169: 600–604

    Google Scholar 

  • Moyse E, Rostène W, Vial M, Leonard K, Mazella J, Kitabgi P, Vincent JP, Beaudet A (1987) Distribution of neurotensin binding sites in rat brain: a light microscopic radiographic study using monoiodo {125I} Tyr3-neurotensin. Neuroscience 22: 525–536

    Google Scholar 

  • Nemeroff CB, Luttinger D, Hernandez DE, Mailman RB, Mason GA, Davis SD, Widerlow E, Frye GD, Kilts CA, Beaumont K, Breese GR, Prange AJ Jr (1983) Interactions of neurotensin with brain dopamine systems: biochemical and behavioral studies. J Pharmacol Exp Ther 225: 337–345

    Google Scholar 

  • Nemeroff CB, Cain ST (1985) Neurotensin-dopamine interactions in the CNS. Trends Pharmacol Sci 6: 201–205

    Google Scholar 

  • Palacios JM, Kuhar MJ (1981) Neurotensin receptors are located on dopamine-containing neurons in rat midbrain. Nature 294: 587–589

    Google Scholar 

  • Pénit-Soria J, Audinat E, Crépel F (1987) Excitation of rat prefrontal cortical neurons by dopamine: an in vitro electrophysiological study. Brain Res 425: 263–274

    Google Scholar 

  • Quirion R (1983) Interactions between neurotensin and dopamine in the brain: an overview. Peptides 4: 609–615

    Google Scholar 

  • Quirion R, Chiueh CC, Everist HD, Pert A (1985) Comparative localization of neurotensin receptors on nigrostriatal and mesolimbic dopaminergic terminals. Brain Res 327: 385–389

    Google Scholar 

  • Randle JC, Bourque CW, Renaud LP (1986) Characterization of spontaneous and evoked inhibitory postsynaptic potentials in rat supraoptic neurosecretory neurons in vitro. J Neurophysiol 56: 1703–1717

    Google Scholar 

  • Scharfman HE, Sarvey JM (1987) Responses to GABA recorded from identified rat visual cortical neurons. Neuroscience 23: 407–422

    Google Scholar 

  • Schwindt PC, Spain WJ, Foehring RC, Stafstrom CE, Chubb MC, Crill WE (1988a) Multiple potassium conductances and their functions in neurons from sensorimotor cortex in vitro. J Neurophysiol 59: 424–449

    Google Scholar 

  • Schwindt PC, Spain WJ, Foehring RC, Chubb MC, Crill WE (1988b) Slow conductances in neurons from cat sensorimotor cortex in vitro and their role in slow excitability changes. J Neurophysiol 59: 450–467

    Google Scholar 

  • Schwindt PC, Spain WJ, Crill E (1989) Long-lasting reduction of excitability by a sodium-dependent potassium current in cat neocortical neurons. J Neurosci 61: 233

    Google Scholar 

  • Seroogy KB, Mehta A, Fallon JH (1987) Neurotensin and cholecystokinin coexistence within neurons of the ventral mesencephalon: projections to forebrain. Exp Brain Res 68: 277–289

    Google Scholar 

  • Stafstrom CE, Schwindt PC, Flatman JA, Crill WE (1984) Properties of subthreshold response and action potential recorded in layer V neurons from cat sensorimotor cortex in vitro. J Neurophysiol 52: 244–263

    Google Scholar 

  • Stafstrom CE, Schwindt PC, Chubb MC, Crill WE (1985) Properties of persistent sodium conductance and calcium conductance of layer V neurons from cat sensorimotor cortex in vitro. J Neurophysiol 53: 153–170

    Google Scholar 

  • Stanzione P, Zieglgänsberger W (1983) Action of neurotensin on spinal cord neurons in the rat. Brain Res 268: 111–118

    Google Scholar 

  • Studler JM, Kitabgi P, Tramu G, Hervé D Glowinski J, Tassin JP (1988) Extensive co-localization of neurotensine with dopamine in rat meso-cortico-frontal dopaminergic neurons. Neuropeptides 11: 95–100

    Google Scholar 

  • Uhl GR, Kuhar MJ, Snyder SH (1977) Neurotensin: immunohistochemical localization in rat nervous central system. Proc Natl Acad Sci USA 74: 4059–4063

    Google Scholar 

  • Williams JT, Katayama Y, North A (1979) The action of neurotensin on single myenteric neurones. Eur J Pharmacol 59: 181–186

    Google Scholar 

  • Young SW, Kuhar MJ (1981) Neurotensin receptor localization by light microscopic autoradiography in the rat brain. Brain Res 206: 273–285

    Google Scholar 

  • Young SW, Uhl GR, Kuhar MJ (1978) Iontophoresis of neurotensin in the area of the locus coeruleus. Brain Res 150: 431–435

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. CNRS UA 1121, Laboratoire de Neurobiologie et Neuropharmacologie du Développement, Université Paris-Sud, F-91405, Orsay, France

    E. Audinat, J.-M. Hermel & F. Crépel

Authors
  1. E. Audinat
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J.-M. Hermel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. F. Crépel
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Audinat, E., Hermel, JM. & Crépel, F. Neurotensin-induced excitation of neurons of the rat's frontal cortex studied intracellularly in vitro. Exp Brain Res 78, 358–368 (1989). https://doi.org/10.1007/BF00228907

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00228907

Key words

Search

Navigation