Modulation of Basal Glutamatergic Transmission by Nicotinic Acetylcholine Receptors in Rat Hippocampal Slices

Document Type : Original Article

Authors

1 Department of Physiology, Medical Faculty, Urmia University of Medical Sciences, Urmia, Iran

2 Division of Neuroscience and Biomedical Systems, IBLS, University of Glasgow, Glasgow, G12 8QQ,UK

Abstract

Objective(s)
Nicotinic acetylcholine receptors (nAChRs) regulate epileptiform activity and produce a sustained pro-epileptogenic action within the hippocampal slices. In the present study, we investigated the effect of nAChRs on evoked glutamatergic synaptic transmission in area CA3 and CA1 of rat hippocampal slices to identify possible excitatory circuits through which activation of nAChRs produce their pro-epileptogenic effects.
Materials and Methods
 
Hippocampal slices (400 µm thick) prepared in vitro from male Wistar rats (3-5 weeks), using standard procedures. Following 1 hr equilibration in artificial cerebrospinal fluid (ACSF), slices transferred to an interface recording chamber. Stimulatory electrodes placed within the hilus or Schaffer-collateral pathways and extracellular field recordings made in the stratum radiatum of the CA1 and CA3 regions to investigate evoked synaptic responses.
Results
Bath application of the selective nAChR agonist dimethylphenyl-piperanzinium (DMPP, 30 mM) resulted in a sustained and reversible enhancement of glutamate afferent evoked fEPSP amplitude by 15.7±5.1%            (mean±SEM; n=8 of 12) in the CA3 region of the hippocampus but not in the CA1 (-5.25±8.3%, mean±SEM; n=5).
Conclusion
Activation of nAChRs may produce pro-epileptogenic actions in part through regulating glutamatergic circuits. Difference in nAChR regulation is also evident between different regions of hippocampus.

Keywords

References

1. Jones S, Sudweeks S, Yakel JL. Nicotinic receptors in the brain: correlating physiology with function. Trends Neurosci 1999; 22:555-561.
2. Freedman R, Wetmore C, Stromberg I, Leonard S, Olson L. Alpha-bungarotoxin binding to hippocampal interneurons: immunocytochemical characterization and effects on growth factor expression. J Neurosci 1993; 13:1965-1975.
3. Freund TF, Buzsaki G. Interneurons of the hippocampus. Hippocampus 1996;6: 347-470.
4. Alkondon M, Pereira EF, Barbosa CT, Albuquerque EX. Neuronal nicotinic acetylcholine receptor activation modulates gamma-aminobutyric acid release from CA1 neurons of rat hippocampal slices. J Pharmacol Exp Ther 1997; 283:1396-1411.
5. Frazier CJ, Buhler AV, Weiner JL, Dunwiddie TV. Synaptic potentials mediated via alpha-bungarotoxin-sensitive nicotinic acetylcholine receptors in rat hippocampal interneurons. J Neurosci 1998; 18:8228-8235.
6. Frazier CJ, Rollins YD, Breese CR, Leonard S, Freedman R, Dunwiddie TV. Acetylcholine activates an alpha-bungarotoxin-sensitive nicotinic current in rat hippocampal interneurons, but not pyramidal cells. J Neurosci 1998; 18:1187-1195.
7. McQuiston AR, Madison DV. Nicotinic receptor activation excites distinct subtypes of interneurons in the rat hippocampus. J Neurosci 1999; 19:2887-2896.
8. Ji D, Lape R, Dani JA. Timing and location of nicotinic activity enhances or depresses hippocampal synaptic plasticity. Neuron 2001;31:131-141.
9. Albuquerque EX, Alkondon M, Pereira EF, Castro NG, Schrattenholz A, Barbosa CT, et al. Properties of neuronal nicotinic acetylcholine receptors: pharmacological characterization and modulation of synaptic function. J Pharmacol Exp Ther 1997; 280:1117-1136.
10. Gray R, Rajan AS, Radcliffe KA, Yakehiro M, Dani JA. Hippocampal synaptic transmission enhanced by low concentrations of nicotine. Nature 1996; 383:713-716.
11. Ji D, Dani JA. Inhibition and disinhibition of pyramidal neurons by activation of nicotinic receptors on hippocampal interneurons. J Neurophysiol 2000; 83:2682-2690.
12. Barrantes GE, Murphy CT, Westwick J, Wonnacott S. Nicotine increases intracellular calcium in rat hippocampal neurons via voltage-gated calcium channels. Neurosci Lett 1995; 196:101-104.
13. Colquhoun LM, Patrick JW. Pharmacology of neuronal nicotinic acetylcholine receptor subtypes. Adv Pharmacol 1997; 39:191-220.
14. Vogt KE, Regehr WG. Cholinergic modulation of excitatory synaptic transmission in the CA3 area of the hippocampus. J Neurosci 2001; 21:75-83.
15. Jones S, Yakel JL. Functional nicotinic ACh receptors on interneurones in the rat hippocampus. J Physiol 1997; 504:603-610.
16. Aceto MD, Bentley HC, Dembinski JR. Effects of ganglion blocking agents on nicotine extensor convulsions and lethality in mice. Br J Pharmacol 1969;37:104-111.
17. Miner LL, Collins AC. Strain comparison of nicotine-induced seizure sensitivity and nicotinic receptors. Pharmacol Biochem Behav 1989; 33:469-475.
18. Steinlein OK, Mulley JC, Propping P, Wallace RH, Phillips HA, Sutherland GR, et al. A missense mutation in the neuronal nicotinic acetylcholine receptor alpha 4 subunit is associated with autosomal dominant nocturnal frontal lobe epilepsy. Nat Genet 1995;11:201-203.
19. Steinlein O, Sander T, Stoodt J, Kretz R, Janz D, Propping P. Possible association of a silent polymorphism in the neuronal nicotinic acetylcholine receptor subunit alpha 4 with common idiopathic generalized epilepsies. Am J Med Genet 1997; 74:445-449.
20. Steinlein OK. Neuronal nicotinic receptors in human epilepsy. Eur J Pharmacol 2000; 393:243-247.
21. Steinlein OK. Genetic disorders caused by mutated acetylcholine receptors. Life Sci 2007; 80:2186-2190.
22. Roshan-Milani S, Ferrigan L, Khoshnood MJ, Davies CH, Cobb SR. Regulation of epileptiform activity in hippocampus by nicotinic acetylcholine receptor activation. Epilepsy Res 2003; 56:51-65.
23. Traub RD, Miles R. Multiple modes of neuronal population activity emerge after modifying specific synapses in a model of the CA3 region of the hippocampus. Ann N Y Acad Sci 1991; 627:277-290.
24. Staley KJ, Longacher M, Bains JS, Yee A. Presynaptic modulation of CA3 network activity. Nat Neurosci 1998;1:201-209.
25. Bains JS, Longacher JM, Staley KJ. Reciprocal interactions between CA3 network activity and strength of recurrent collateral synapses. Nat Neurosci 1999; 2:720-726.
26. Morton RA, Davies CH. Regulation of muscarinic acetylcholine receptor-mediated synaptic responses by adenosine receptors in the rat hippocampus. J Physiol 1997; 502:75-90.
27. McGehee DS, Heath MJ, Gelber S, Devay P, Role LW. Nicotine enhancement of fast excitatory synaptic transmission in CNS by presynaptic receptors. Science 1995; 269:1692-1696.
28. Radcliffe KA, Dani JA. Nicotinic stimulation produces multiple forms of increased glutamatergic synaptic transmission. J Neurosci 1998; 18:7075-7083.
29. Kostopoulos G, Psarropoulou C. Increased postsynaptic excitability in hippocampal slices from the tottering epileptic mutant mouse. Epilepsy Res 1990; 6:49-55.
30. Mann EO, Greenfield SA. Novel modulatory mechanisms revealed by the sustained application of nicotine in the guinea-pig hippocampus in vitro. J Physiol 2003; 551:539-550.
31. Psarropoulou C, Boivin M, Laudadio MA. Nicotinic effects on excitatory field potentials recorded from the immature CA3 area of rat hippocampal slices. Exp Brain Res 2003; 152:353-360.
32. Liu ZW, Yang S, Zhang YX, Liu CH. Presynaptic alpha-7 nicotinic acetylcholine receptors modulate excitatory synaptic transmission in hippocampal neurons. Sheng Li Xue Bao 2003; 55:731-735.
33. Hasselmo ME, Schnell E. Laminar selectivity of the cholinergic suppression of synaptic transmission in rat hippocampal region CA1: computational modeling and brain slice physiology. J Neurosci 1994; 14:3898-3914.
 
 
Iranian Journal of Basic Medical Sciences
Volume 11, Issue 4 - Serial Number 4
October 2009
Pages 221-228

Files

Share

How to cite

Statistics