Nicotinic activity stabilizes convergence of nicotinic and GABAergic synapses on filopodia of hippocampal interneurons
Abstract
Nicotinic acetylcholine receptors containing alpha7 subunits occupy pre- and postsynaptic sites in the adult hippocampus. We find that embryonic hippocampal slices in culture display the receptors most prominently on interneurons where they form clusters localized in part on filopodia. The receptors often co-distribute specifically with GABAA receptors. In septal-hippocampal co-cultures, the filopodia become co-innervated by cholinergic and GABAergic terminals abutting the receptor clusters. Nicotinic transmission appears to stabilize the cholinergic contacts: pharmacological blockade of the alpha7-containing nicotinic receptors increases the rate of filopodia movement and decreases the incidence of the clusters being adjacent to cholinergic terminals. Immunostaining fresh hippocampal slices from neonatal rat pups confirms that cholinergic and GABAergic terminals contact alpha7-containing nicotinic receptor clusters in vivo, and the clusters appear to include filopodial sites. The results indicate a convergence of nicotinic and GABAergic input at specific sites on developing hippocampal interneurons and suggest that synaptic activity helps stabilize the nicotinic contribution.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Nicotinic acetylcholine receptors contribute to the maturation of GABAergic and glutamatergic synapses.
“Recent studies have also shown that nAChRs contribute to the maturation of GABAergic (Kawai et al., 2002; Zago et al., 2006) and glutamatergic (Lozada et al., 2012a, b) synapses, highlighting an important role for ACh signaling in synaptic development, as well as neuronal pathfinding and target selection (reviewed in (Role and Berg, 1996).”
From Acetylcholine as a Neuromodulator: Cholinergic Signaling Shapes Nervous System Function and Behavior (2012) · cites this paper as Zago et al., 2006
Cites
1 retracted
Quik, M., Cohen, R., AUDHYA, T. K., et al. (1990) · Neuroscience · doi:10.1016/0306-4522(90)90228-v · Cited by 10 · see citing works
RetractedInterneurons of the hippocampus
Freund, T. F., & Buzsáki, G. (1998) · Hippocampus · doi:10.1002/(sici)1098-1063(1996)6:4 · Cited by 3,423 · see citing works
A simple method for organotypic cultures of nervous tissue
Stoppini, L., Buchs, P., & Muller, D. (1991) · Journal of Neuroscience Methods · doi:10.1016/0165-0270(91)90128-m · Cited by 3,097 · see citing works
Séguéla, P., Wadiche, J. I., Dineley‐Miller, K., Dani, J., & Jw, P. (1993) · Journal of Neuroscience · doi:10.1523/jneurosci.13-02-00596.1993 · Cited by 1,471 · see citing works
GABA-containing neurons in the septum control inhibitory interneurons in the hippocampus
Freund, T. F., & Antal, M. (1988) · Nature · doi:10.1038/336170a0 · Cited by 1,283 · see citing works
Nicotine enhancement of fast excitatory synaptic transmission in CNS by presynaptic receptors
McGehee, D. S., Heath, M. J. S., Gelber, S., Devay, P., & Role, L. W. (1995) · Science · doi:10.1126/science.7569895 · Cited by 1,070 · see citing works
Hippocampal synaptic transmission enhanced by low concentrations of nicotine
Gray, R. G. F., Rajan, A. S., Radcliffe, K. A., Yakehiro, M., & Dani, J. A. (1996) · Nature · doi:10.1038/383713a0 · Cited by 947 · see citing works
Evidence for a Role of Dendritic Filopodia in Synaptogenesis and Spine Formation
Ziv, N. E., & Smith, S. J. (1996) · Neuron · doi:10.1016/s0896-6273(00)80283-4 · Cited by 863 · see citing works
Synaptogenesis Via Dendritic Filopodia in Developing Hippocampal Area CA1
Fiala, J. C., Feinberg, M., Popov, V., & Harris, K. M. (1998) · The Journal of Neuroscience · doi:10.1523/jneurosci.18-21-08900.1998 · Cited by 758 · see citing works
Ganguly, K., Schinder, A. F., Wong, S. T., & Poo, M. (2001) · Cell · doi:10.1016/s0092-8674(01)00341-5 · Cited by 719 · see citing works
Genesis of dendritic spines: insights from ultrastructural and imaging studies
Yuste, R., & Bonhoeffer, T. (2004) · Nature reviews. Neuroscience · doi:10.1038/nrn1300 · Cited by 628 · see citing works
Nicotinic acetylcholine receptors and the regulation of neuronal signalling
Dajas‐Bailador, F., & Wonnacott, S. (2004) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2004.04.006 · Cited by 618 · see citing works
The Dynamics of Dendritic Structure in Developing Hippocampal Slices
Dailey, M. E., & Smith, S. J. (1996) · The Journal of Neuroscience · doi:10.1523/jneurosci.16-09-02983.1996 · Cited by 611 · see citing works
McKinney, M., Coyle, J. T., & Hedreen, J. C. (1983) · The Journal of Comparative Neurology · doi:10.1002/cne.902170109 · Cited by 463 · see citing works
Nicotinic receptors in the brain: correlating physiology with function
Jones, S., Sudweeks, S. N., & Yakel, J. L. (1999) · Trends in Neurosciences · doi:10.1016/s0166-2236(99)01471-x · Cited by 447 · see citing works
Glutamate receptors regulate actin-based plasticity in dendritic spines
Fischer, M., Kaech, S., Wagner, U., Brinkhaus, H., & Matus, A. (2000) · Nature Neuroscience · doi:10.1038/78791 · Cited by 446 · see citing works
Bertrand, D., Galzi, J., Devillers‐Thiéry, A., Bertrand, S., & Changeux, J. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.15.6971 · Cited by 390 · see citing works
Nolte, J. (2007) · Elsevier eBooks · doi:10.1016/b978-0-323-03409-8.50009-9 · Cited by 384 · see citing works
Ultrastructural Distribution of the α7 Nicotinic Acetylcholine Receptor Subunit in Rat Hippocampus
Fabian‐Fine, R., Skehel, P., Errington, M. L., Davies, H. A., Sher, E., Stewart, M. G., & Fine, A. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-20-07993.2001 · Cited by 361 · see citing works
Volume transmission in the CNS and its relevance for neuropsychopharmacology
Zoli, M. (1999) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(99)01343-7 · Cited by 346 · see citing works
Alkondon, M., Pereira, E. F. R., Eisenberg, H. M., & Albuquerque, E. X. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-07-02693.1999 · Cited by 332 · see citing works
Morphological analysis of dendritic spine development in primary cultures of hippocampal neurons
Papa, M., Bundman, M. C., Greenberger, V., & Segal, M. (1995) · Journal of Neuroscience · doi:10.1523/jneurosci.15-01-00001.1995 · Cited by 330 · see citing works
Frazier, C. J., Buhler, A. V., Weiner, J. L., & Dunwiddie, T. V. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-20-08228.1998 · Cited by 329 · see citing works
Alkondon, M., Pereira, E. F. R., Barbosa, C. T. F., & Albuquerque, E. X. (1997) · PubMed · Cited by 326 · see citing works
Kittler, J. T., & Moss, S. J. (2003) · Current Opinion in Neurobiology · doi:10.1016/s0959-4388(03)00064-3 · Cited by 301 · cited 2× · see citing works
“…GABAergic transmission also displays plasticity (Lu et al., 2000; Gubellini et al., 2001; Kirischuk et al., 2002; Wang et al., 2003; Bauer and LeDoux, 2004), and GABAAR function can be regulated (Kawaguchi and Hirano, 2002; Kittler and Moss, 2003) through mechanisms likely to be calcium-dependent.”
BackgroundLu, Y. M., Mansuy, I. M., Kandel, E. R., & Roder, J. (2000) · Neuron · doi:10.1016/s0896-6273(00)81150-2 · Cited by 274 · see citing works
Functional nicotinic ACh receptors on interneurones in the rat hippocampus
Jones, S., & Yakel, J. L. (1997) · The Journal of Physiology · doi:10.1111/j.1469-7793.1997.603bd.x · Cited by 271 · see citing works
Nicotinic Stimulation Produces Multiple Forms of Increased Glutamatergic Synaptic Transmission
Radcliffe, K. A., & Dani, J. A. (1998) · The Journal of Neuroscience · doi:10.1523/jneurosci.18-18-07075.1998 · Cited by 271 · see citing works
Portera-Cailliau, C., Pan, D. T., & Yuste, R. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-18-07129.2003 · Cited by 269 · see citing works
Alkondon, M., Pereira, E. F. R., & Albuquerque, E. X. (1998) · Brain Research · doi:10.1016/s0006-8993(98)00880-4 · Cited by 263 · see citing works
Zhang, Z., Vijayaraghavan, S., & Berg, D. K. (1994) · Neuron · doi:10.1016/0896-6273(94)90161-9 · Cited by 254 · see citing works
Self-citationPugh, P., & Berg, D. K. (1994) · Journal of Neuroscience · doi:10.1523/jneurosci.14-02-00889.1994 · Cited by 252 · see citing works
Self-citationGulyás, A. I., Miettinen, R. A., Jacobowitz, D. M., & Freund, T. F. (1992) · Neuroscience · doi:10.1016/0306-4522(92)90334-x · Cited by 252 · see citing works
Nicotinic Antagonists Enhance Process Outgrowth by Rat Retinal Ganglion Cells in Culture
Lipton, S. A., Frosch, M. P., Phillips, M. D., Tauck, D. L., & Aizenman, E. (1988) · Science · doi:10.1126/science.3344435 · Cited by 225 · see citing works
The α7 nicotinic acetylcholine receptor in neuronal plasticity
Broide, R. S., & Leslie, F. M. (1999) · Molecular Neurobiology · doi:10.1007/bf02741361 · Cited by 210 · see citing works
Freedman, R., Wetmore, C., Strömberg, I., Leonard, S. S., & Olson, L. (1993) · Journal of Neuroscience · doi:10.1523/jneurosci.13-05-01965.1993 · Cited by 202 · see citing works
Nicotinic α7 receptors: Synaptic options and downstream signaling in neurons
Berg, D. K., & Conroy, W. G. (2002) · Journal of Neurobiology · doi:10.1002/neu.10116 · Cited by 198 · see citing works
Self-citationSudweeks, S. N., & Yakel, J. L. (2000) · The Journal of Physiology · doi:10.1111/j.1469-7793.2000.00515.x · Cited by 197 · see citing works
Cholinergic innervation of hippocampal GAD‐ and somatostatin‐immunoreactive commissural neurons
Léránth, C., & Frotscher, M. (1987) · The Journal of Comparative Neurology · doi:10.1002/cne.902610104 · Cited by 189 · see citing works
Presynaptic Nicotinic Receptors Facilitate Monoaminergic Transmission
Li, X., Rainnie, D. G., McCarley, R. W., & Greene, R. W. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-05-01904.1998 · Cited by 176 · see citing works
Liu, Y., Ford, B. D., Mann, M. A., & Fischbach, G. D. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-15-05660.2001 · Cited by 157 · see citing works
Hefft, S., Hulo, S., Bertrand, D., & Müller, D. (1999) · The Journal of Physiology · doi:10.1111/j.1469-7793.1999.769ab.x · Cited by 152 · see citing works
Guo, J., Tredway, T. L., & Chiappinelli, V. A. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-06-01963.1998 · Cited by 143 · see citing works
Glutamate regulates actin-based motility in axonal filopodia
Chang, S., & Camilli, P. V. D. (2001) · Nature Neuroscience · doi:10.1038/90489 · Cited by 141 · see citing works
Kawai, H., Zago, W., & Berg, D. K. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-18-07903.2002 · Cited by 140 · see citing works
Self-citationWang, J., Liu, S., Haditsch, U., Tu, W., Cochrane, K., Ahmadian, G., Tran, L., Paw, J., Wang, Y., Mansuy, I. M., et al. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-03-00826.2003 · Cited by 134 · see citing works
Khiroug, L. S., Giniatullin, R. A., Klein, R. C., Fayuk, D. A., & Yakel, J. L. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-27-09024.2003 · Cited by 124 · see citing works
Nicotinic receptors in the brain
Vidal, C. (1996) · Molecular and Chemical Neuropathology · doi:10.1007/bf02815199 · Cited by 118 · see citing works
Development of the α7 nicotinic cholinergic receptor in rat hippocampal formation
Adams, C. E., Broide, R. S., Chen, Y.-L., Winzer‐Serhan, U. H., Henderson, T. A., Leslie, F. M., & Freedman, R. (2002) · Developmental Brain Research · doi:10.1016/s0165-3806(02)00547-3 · Cited by 107 · see citing works
Heterosynaptic Long-Term Potentiation of Inhibitory Interneurons in the Lateral Amygdala
Bauer, E. P., & LeDoux, J. E. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.3567-04.2004 · Cited by 105 · see citing works
Wong, W. T., & Wong, R. (2001) · Nature Neuroscience · doi:10.1038/85987 · Cited by 102 · see citing works
Kawaguchi, S., & Hirano, T. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-10-03969.2002 · Cited by 99 · see citing works
Levy, R. B., & Aoki, C. J. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-12-05001.2002 · Cited by 88 · see citing works
Kirischuk, S., Clements, J. D., & Grantyn, R. (2002) · The Journal of Physiology · doi:10.1113/jphysiol.2002.021576 · Cited by 86 · see citing works
Nicotinic Acetylcholine Receptors
Wiley, J., York, N., Colquhoun, D., Unwin, P. N. T., Shelley, C., Hatton, C., & Sivilotti, L. G. (2004) · Encyclopedic Dictionary of Genetics, Genomics and Proteomics · doi:10.1002/0471684228.egp08474 · Cited by 79 · see citing works
Molinari, E. J., Delbono, O., Messi, M. L., Renganathan, M., Arnerić, S. P., Sullivan, J. P., & Gopalakrishnan, M. (1998) · European Journal of Pharmacology · doi:10.1016/s0014-2999(98)00084-3 · Cited by 75 · see citing works
Activity‐ and age‐dependent GABAergic synaptic plasticity in the developing rat hippocampus
Gubellini, P., Ben‐Ari, Y., & Gaïarsa, J. (2001) · European Journal of Neuroscience · doi:10.1046/j.0953-816x.2001.01823.x · Cited by 68 · see citing works
Synaptic Potentials Mediated by α7 Nicotinic Acetylcholine Receptors in Supraoptic Nucleus
Hatton, G. I., & Yang, Q. Z. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-01-00029.2002 · Cited by 63 · see citing works
Buckmaster, P. S., Yamawaki, R. M., & Zhang, G. F. (2002) · The Journal of Comparative Neurology · doi:10.1002/cne.10183 · Cited by 62 · see citing works
The hypothesis of an ambient level of acetylcholine in the central nervous system
Descarries, L. (1998) · Journal of Physiology-Paris · doi:10.1016/s0928-4257(98)80013-2 · Cited by 58 · see citing works
Ridley, D. L., Rogers, A. T., & Wonnacott, S. (2001) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0704207 · Cited by 58 · see citing works
Saito, Y., Song, W., & Murakami, F. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-22-08792.1997 · Cited by 38 · see citing works
Neuronal Acetylcholine Receptors
Skok, V. I., Selyanko, A. A., & Derkach, V. A. (1989) · Springer eBooks · doi:10.1007/978-1-4684-1668-8 · Cited by 28 · see citing works
Heimrich, B., & Frotscher, M. (1993) · Neuroscience · doi:10.1016/0306-4522(93)90531-j · Cited by 26 · see citing works
Developmental organization of neurophysin neurons in the human brain
Mai, J. K., Lensing‐Höhn, S., Ende, A., & Sofroniew, M. V. (1997) · The Journal of Comparative Neurology · doi:10.1002/(sici)1096-9861(19970901)385:3 · Cited by 25 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Acetylcholine as a Neuromodulator: Cholinergic Signaling Shapes Nervous System Function and Behavior
Picciotto, M. R., Higley, M. J., & Mineur, Y. S. (2012) · Neuron · doi:10.1016/j.neuron.2012.08.036 · Cited by 1,404 · see citing works
Chocyk, A., Bobula, B., Dudys, D., Przyborowska, A., Majcher-Maślanka, I., Hess, G., & Wędzony, K. (2013) · European Journal of Neuroscience · doi:10.1111/ejn.12208 · Cited by 153 · see citing works
Cholinergic control of GABA release: emerging parallels between neocortex and hippocampus
Lawrence, J. J. (2008) · Trends in Neurosciences · doi:10.1016/j.tins.2008.03.008 · Cited by 115 · see citing works
Farías, G. G., Vallés, A. S., Colombres, M., Godoy, J. A., Toledo, E. M., Lukas, R. J., Barrantes, F. J., & Inestrosa, N. C. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.3934-06.2007 · Cited by 108 · see citing works
- Authors
- Zago, W. M., Massey, K. A., & Berg, D. K.
- Affiliations
- University of California San Diego (US)
- Corresponding author
- Berg, Darwin K.
- ORCID
- Zago, Wagner M.
- Venue
- Molecular and Cellular Neuroscience
- Publisher
- Elsevier BV
- Published
- 2006-03
- Volume
- 31
- Issue
- 3
- Pages
- 549-559
- ISSN
- 1044-7431 (ISSN-L)
- OpenAlex
- W2171712409
- Cited by
- 24
- References
- 65
- Citations by year
- 2025: 1 · 2018: 2 · 2017: 1 · 2015: 1 · 2014: 1 · 2013: 3 · 2012: 2
- FWCI
- 1.36
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular and Cellular Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (NS12601, NS35469, R01NS012601, R01NS035469)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- nicotinic acetylcholine receptors, alpha7 nicotinic acetylcholine receptor, GABAA receptor, synaptic convergence, filopodia, hippocampal interneurons, cholinergic nerve terminals, GABAergic terminals, nicotinic transmission
- MeSH terms
- Acetylcholine, Animals, Animals, Newborn, Cholinergic Fibers, gamma-Aminobutyric Acid, Hippocampus, Interneurons, Synaptic Transmission, Organ Culture Techniques, Pseudopodia, Receptors, GABA-A, Receptors, Nicotinic, Synapses, Rats, Sprague-Dawley, Presynaptic Terminals, Nicotinic Antagonists, GABA Antagonists, Coculture Techniques, Receptor Cross-Talk, Dendritic Spines, Rats, alpha7 Nicotinic Acetylcholine Receptor
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review