A cholinergic trigger drives learning-induced plasticity at hippocampal synapses

Abstract

Learning induces plastic changes in synapses. However, the regulatory molecules that orchestrate learning-induced synaptic changes are largely unknown. Although it is well established that cholinergic inputs from the medial septum modulate learning and memory, evidence for the cholinergic regulation of learning-induced synaptic plasticity is lacking. Here we find that the activation of muscarinic acetylcholine (ACh) receptors (mAChRs) mediates the contextual fear learning-driven strengthening of hippocampal excitatory pyramidal synapses through the synaptic incorporation of AMPA-type glutamate receptors (AMPARs). Contextual fear learning also enhances the strength of inhibitory synapses on hippocampal pyramidal CA1 neurons, in a manner mediated by the activation of, not mAChRs, but, nicotinic AChRs (nAChRs). We observe a significant correlation between the learning-induced increases in excitatory and inhibitory synaptic strength at individual pyramidal neurons. Understanding the mechanisms underlying cholinergic regulation of learning-induced hippocampal synaptic plasticity may help the development of new therapies for cognitive disorders.

References 44

1. 1.

   Drever B. D., Riedel G. & Platt B. The cholinergic system and hippocampal plasticity. Behav. Brain Res. 221, 505–514 (2011 ).

   Not in our library10.1016/j.bbr.2010.11.037

2. 2.

   Blokland A. Acetylcholine: a neurotransmitter for learning and memory? Brain Res. Brain Res. Rev. 21, 285–300 (1995 ).

   Not in our library10.1016/0165-0173(95)00016-x

3. 3.

   Hasselmo M. E. Neuromodulation: acetylcholine and memory consolidation. Trends Cogn. Sci. 3, 351–359 (1999 ).

   Not in our library10.1016/s1364-6613(99)01365-0

4. 4.

   Shinoe T., Matsui M., Taketo M. M. & Manabe T. Modulation of synaptic plasticity by physiological activation of M1 muscarinic acetylcholine receptors in the mouse hippocampus. J. Neurosci. 25, 11194–11200 (2005 ).

   Not in our library10.1523/jneurosci.2338-05.2005

5. 5.

   Gu Z. & Yakel J. L. Timing-dependent septal cholinergic induction of dynamic hippocampal synaptic plasticity. Neuron 71, 155–165 (2011 ).

   Not in our library10.1016/j.neuron.2011.04.026

6. 6.

   Fernández de Sevilla D., Núñez A., Borde M., Malinow R. & Buño W. Cholinergic-mediated IP3-receptor activation induces long-lasting synaptic enhancement in CA1 pyramidal neurons. J. Neurosci. 28, 1469–1478 (2008 ).

   Not in our library10.1523/jneurosci.2723-07.2008

7. 7.

   Ovsepian S. V., Anwyl R. & Rowan M. J. Endogenous acetylcholine lowers the threshold for long-term potentiation induction in the CA1 area through muscarinic receptor activation: in vivo study. Eur. J. Neurosci. 20, 1267–1275 (2004 ).

   Not in our library10.1111/j.1460-9568.2004.03582.x

8. 8.

   Aigner T. G. Pharmacology of memory: cholinergic-glutamatergic interactions. Curr. Opin. Neurobiol. 5, 155–160 (1995 ).

   Not in our library10.1016/0959-4388(95)80021-2

9. 9.

   Cole C. J. et al. MEF2 negatively regulates learning-induced structural plasticity and memory formation. Nat. Neurosci. 15, 1255–1264 (2012 ).

   Not in our library10.1038/nn.3189

10. 10.

    Miyazaki T. et al. Disrupted cortical function underlies behavior dysfunction due to social isolation. J. Clin. Invest. 122, 2690–2701 (2012 ).

    Not in our library10.1172/jci63060

11. 11.

    Kessels H. W. & Malinow R. Synaptic AMPA receptor plasticity and behavior. Neuron 61, 340–350 (2009 ).

    Not in our library10.1016/j.neuron.2009.01.015

12. 12.

    Takahashi T., Svoboda K. & Malinow R. Experience strengthening transmission by driving AMPA receptors into synapses. Science 299, 1585–1588 (2003 ).

    Not in our library10.1126/science.1079886

13. 13.

    Clem R. L. & Barth A. Pathway-specific trafficking of native AMPARs by in vivo experience. Neuron 49, 663–670 (2006 ).

    Not in our library10.1016/j.neuron.2006.01.019

14. 14.

    Jitsuki S. et al. Serotonin mediates cross-modal reorganization of cortical circuits. Neuron 69, 780–792 (2011 ).

    Not in our library10.1016/j.neuron.2011.01.016

15. 15.

    Miyazaki T. et al. Developmental AMPA receptor subunit specificity during experience-driven synaptic plasticity in the rat barrel cortex. Brain Res. 1435, 1–7 (2012 ).

    Not in our library10.1016/j.brainres.2011.11.033

16. 16.

    Mitsushima D., Ishihara K., Sano A., Kessels H. W. & Takahashi T. Contextual learning requires synaptic AMPA receptor delivery in the hippocampus. Proc. Natl Acad. Sci. USA 108, 12503–12508 (2011 ).

    Not in our library10.1073/pnas.1104558108

17. 17.

    Whitlock J. R., Heynen A. J., Shuler M. G. & Bear M. F. Learning induces long-term potentiation in the hippocampus. Science 313, 1093–1097 (2006 ).

    Not in our library10.1126/science.1128134

18. 18.

    Rumpel S., LeDoux J., Zador A. & Malinow R. Postsynaptic receptor trafficking underlying a form of associative learning. Science 308, 83–88 (2005 ).

    Not in our library10.1126/science.1103944

19. 19.

    Lee H. K. et al. Phosphorylation of the AMPA receptor GluR1 subunit is required for synaptic plasticity and retention of spatial memory. Cell 112, 631–643 (2003 ).

    Not in our library10.1016/s0092-8674(03)00122-3

20. 20.

    Cui Y. et al. Neurofibromin regulation of ERK signaling modulates GABA release and learning. Cell 135, 549–560 (2008 ).

    Not in our library10.1016/j.cell.2008.09.060

21. 21.

    Auerbach J. M. & Segal M. Muscarinic receptors mediating depression and long-term potentiation in rat hippocampus. J. Physiol. 492, 479–493 (1996 ).

    Not in our library10.1113/jphysiol.1996.sp021323

22. 22.

    Hayashi Y. et al. Driving AMPA receptors into synapses by LTP and CaMKII: requirement for GluR1 and PDZ domain interaction. Science 287, 2262–2267 (2000 ).

    Not in our library10.1126/science.287.5461.2262

23. 23.

    Boehm J. et al. Synaptic incorporation of AMPA receptors during LTP is controlled by a PKC phosphorylation site on GluR1. Neuron 51, 213–225 (2006 ).

    Not in our library10.1016/j.neuron.2006.06.013

24. 24.

    Dobrunz L. E. & Stevens C. F. Heterogeneity of release probability, facilitation, and depletion at central synapses. Neuron 18, 995–1008 (1997 ).

    Not in our library10.1016/s0896-6273(00)80338-4

25. 25.

    Debanne D., Guerineau N. C., Gahwiler B. H. & Thompson S. M. Paired-pulse facilitation and depression at unitary synapses in rat hippocampus: quantal fluctuation affects subsequent release. J. Physiol. 491, 163–176 (1996 ).

    Not in our library10.1113/jphysiol.1996.sp021204

26. 26.

    Buño W., Cabezas C. & Fernández de Sevilla D. Presynaptic muscarinic control of glutamatergic synaptic transmission. J. Mol. Neurosci. 30, 161–164 (2006 ).

    Not in our library10.1385/jmn:30:1:161

27. 27.

    Harnett K. M. et al. Signal transduction in esophageal and LES circular muscle contraction. Yale J. Biol. Med. 72, 153–168 (1999 ).

    Not in our library

28. 28.

    Power J. M. & Sah P. Nuclear calcium signaling evoked by cholinergic stimulation in hippocampal CA1 pyramidal neurons. J. Neurosci. 22, 3454–3462 (2002 ).

    Not in our library10.1523/jneurosci.22-09-03454.2002

29. 29.

    Lee H. K., Barbarosie M., Kameyama K., Bear M. F. & Huganir R. L. Regulation of distinct AMPA receptor phosphorylation sites during bidirectional synaptic plasticity. Nature 405, 955–959 (2000 ).

    Not in our library10.1038/35016089

30. 30.

    Lisman J., Schulman H. & Cline H. The molecular basis of CaMKII function in synaptic and behavioural memory. Nat. Rev. Neurosci. 3, 175–190 (2002 ).

    Not in our library10.1038/nrn753

31. 31.

    Derkach V. A., Oh M. C., Guire E. S. & Soderling T. R. Regulatory mechanisms of AMPA receptors in synaptic plasticity. Nat. Rev. Neurosci. 8, 101–113 (2007 ).

    Not in our library10.1038/nrn2055

32. 32.

    Séguéla P., Wadiche J., Dineley-Miller K., Dani J. A. & Patrick J. W. Molecular cloning, functional properties, and distribution of rat brain α7: a nicotinic cation channel highly permeable to calcium. J. Neurosci. 13, 596–604 (1993 ).

    Not in our library10.1523/jneurosci.13-02-00596.1993

33. 33.

    Buzsáki G. et al. Nucleus basalis and thalamic control of neocortical activity in the freely moving rat. J. Neurosci. 8, 4007–4026 (1988 ).

    Not in our library10.1523/jneurosci.08-11-04007.1988

34. 34.

    Izquierdo I. et al. Mechanisms for memory types differ. Nature 393, 635–636 (1998 ).

    Not in our library10.1038/31371

35. 35.

    Hu H. et al. Emotion enhances learning via norepinephrine regulation of AMPA-receptor trafficking. Cell 131, 160–173 (2007 ).

    Not in our library10.1016/j.cell.2007.09.017

36. 36.

    Han J. H. et al. Selective erasure of a fear memory. Science 323, 1492–1496 (2009 ).

    Not in our library10.1126/science.1164139

37. 37.

    Petersen R. C. et al. Vitamin E and donepezil for the treatment of mild cognitive impairment. N. Engl. J. Med. 352, 2379–2388 (2005 ).

    Not in our library10.1056/nejmoa050151

38. 38.

    Winblad B. et al. Donepezil in patients with severe Alzheimer’s disease: double-blind, parallel-group, placebo-controlled study. Lancet 367, 1057–1065 (2006 ).

    Not in our library10.1016/s0140-6736(06)68350-5

39. 39.

    Farias G. G. et al. M1 muscarinic receptor activation protects neurons from beta-amyloid toxicity. A role for Wnt signaling pathway. Neurobiol. Dis. 17, 337–348 (2004 ).

    Not in our library10.1016/j.nbd.2004.07.016

40. 40.

    Grassi F. et al. Amyloid β(1-42) peptide alters the gating of human and mouse α-bungarotoxin-sensitive nicotinic receptors. J. Physiol. 547, 147–157 (2003 ).

    Not in our library10.1113/jphysiol.2002.035436

Cited by papers we hold 5

• Inconsistencies in atlas-based volumetric measures of the human nucleus basalis of Meynert: A need for high-resolution alternatives · 2022
  Not checked
• The Biology and Pathobiology of Glutamatergic, Cholinergic, and Dopaminergic Signaling in the Aging Brain · 2021
  No notice
• Neuromodulated Spike-Timing-Dependent Plasticity, and Theory of Three-Factor Learning Rules · 2016
  No notice
• Therapies for Prevention and Treatment of Alzheimer’s Disease · 2016
  No notice
• Activation of Muscarinic M1 Acetylcholine Receptors Induces Long-Term Potentiation in the Hippocampus · 2015
  No notice

Reads

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.