Synaptic Plasticity, Metaplasticity and Depression

Overview

Journal Curr Neuropharmacol

Publisher Bentham Science Publishers

Date 2016 Feb 3

PMID 26830964

Citations 40

Authors

Linnea R Vose

Patric K Stanton

Affiliations

Soon will be listed here.

Abstract

The development of a persistent depressive affective state has for some time been thought to result from persistent alterations in neurotransmitter-mediated synaptic transmission. While the identity of those transmitters has changed over the years, the literature has lacked mechanistic connections between the neurophysiological mechanisms they regulate, and how these mechanisms alter neuronal function, and, hence, affective homeostasis. This review will examine recent work that suggests that both long-term activity-dependent changes in synaptic strength ("plasticity"), and shifting set points for the ease of induction of future long-term changes ("metaplasticity"), may be critical to establishing and reversing a depressive behavioral state. Activitydependent long-term synaptic plasticity involves both strengthening and weakening of synaptic connections associated with a dizzying array of neurochemical alterations that include synaptic insertion and removal of a number of subtypes of AMPA, NMDA and metabotropic glutamate receptors, changes in presynaptic glutamate release, and structural changes in dendritic spines. Cellular mechanisms of metaplasticity are far less well understood. Here, we will review the growing evidence that long-term synaptic changes in glutamatergic transmission, in brain regions that regulate mood, are key determinants of affective homeostasis and therapeutic targets with immense potential for drug development.

Citing Articles

[Mechanisms of action of antidepressive pharmacotherapy: brain and mind-body and environment].

Spangemacher M, Reinwald J, Adolphi H, Kartner L, Mertens L, Schmitz C Nervenarzt. 2025; 96(2):119-127.

PMID: 39821675 PMC: 11876238. DOI: 10.1007/s00115-024-01786-3.

Neural Geometrodynamics, Complexity, and Plasticity: A Psychedelics Perspective.

Ruffini G, Lopez-Sola E, Vohryzek J, Sanchez-Todo R Entropy (Basel). 2024; 26(1).

PMID: 38275498 PMC: 11154528. DOI: 10.3390/e26010090.

Mitochondrial and Cellular Function in Fibroblasts, Induced Neurons, and Astrocytes Derived from Case Study Patients: Insights into Major Depression as a Mitochondria-Associated Disease.

Cardon I, Grobecker S, Kucukoktay S, Bader S, Jahner T, Nothdurfter C Int J Mol Sci. 2024; 25(2).

PMID: 38256041 PMC: 10815943. DOI: 10.3390/ijms25020963.

The effect of ketamine on synaptic mistuning induced by impaired glutamate reuptake.

Vazquez-Juarez E, Srivastava I, Lindskog M Neuropsychopharmacology. 2023; 48(13):1859-1868.

PMID: 37301901 PMC: 10584870. DOI: 10.1038/s41386-023-01617-0.

Astrocytes as Context for the Involvement of Myelin and Nodes of Ranvier in the Pathophysiology of Depression and Stress-Related Disorders.

Miguel-Hidalgo J J Psychiatr Brain Sci. 2023; 8.

PMID: 36866235 PMC: 9976698. DOI: 10.20900/jpbs.20230001.

References

Alfarez D, De Simoni A, Velzing E, Bracey E, Joels M, Edwards F . Corticosterone reduces dendritic complexity in developing hippocampal CA1 neurons. Hippocampus. 2009; 19(9):828-36. DOI: 10.1002/hipo.20566. View

Fuchs E, Flugge G . Chronic social stress: effects on limbic brain structures. Physiol Behav. 2003; 79(3):417-27. DOI: 10.1016/s0031-9384(03)00161-6. View

Rasmussen K, Lineberry T, Galardy C, Kung S, Lapid M, Palmer B . Serial infusions of low-dose ketamine for major depression. J Psychopharmacol. 2013; 27(5):444-50. DOI: 10.1177/0269881113478283. View

Jafari M, Seese R, Babayan A, Gall C, Lauterborn J . Glucocorticoid receptors are localized to dendritic spines and influence local actin signaling. Mol Neurobiol. 2012; 46(2):304-15. PMC: 3973133. DOI: 10.1007/s12035-012-8288-3. View

Pecknold J, McClure D, Appeltauer L, Wrzesinski L, Allan T . Treatment of anxiety using fenobam (a nonbenzodiazepine) in a double-blind standard (diazepam) placebo-controlled study. J Clin Psychopharmacol. 1982; 2(2):129-33. View

Cartmell J, Kemp J, Alexander S, Shinozaki H, Kendall D . Modulation of cyclic AMP formation by putative metabotropic receptor agonists. Br J Pharmacol. 1994; 111(1):364-9. PMC: 1910051. DOI: 10.1111/j.1476-5381.1994.tb14069.x. View

Meador K . The basic science of memory as it applies to epilepsy. Epilepsia. 2007; 48 Suppl 9:23-5. DOI: 10.1111/j.1528-1167.2007.01396.x. View

van Schalkwijk F, Blessinga A, Willemen A, van der Werf Y, Schuengel C . Social support moderates the effects of stress on sleep in adolescents. J Sleep Res. 2015; 24(4):407-13. DOI: 10.1111/jsr.12298. View

Zalutsky R, Nicoll R . Comparison of two forms of long-term potentiation in single hippocampal neurons. Science. 1990; 248(4963):1619-24. DOI: 10.1126/science.2114039. View

10.

Rocher C, Spedding M, Munoz C, Jay T . Acute stress-induced changes in hippocampal/prefrontal circuits in rats: effects of antidepressants. Cereb Cortex. 2004; 14(2):224-9. DOI: 10.1093/cercor/bhg122. View

11.

Mayer M, Westbrook G, Vyklicky Jr L . Sites of antagonist action on N-methyl-D-aspartic acid receptors studied using fluctuation analysis and a rapid perfusion technique. J Neurophysiol. 1988; 60(2):645-63. DOI: 10.1152/jn.1988.60.2.645. View

12.

Sapolsky R . The possibility of neurotoxicity in the hippocampus in major depression: a primer on neuron death. Biol Psychiatry. 2000; 48(8):755-65. DOI: 10.1016/s0006-3223(00)00971-9. View

13.

Dumas T . Postnatal alterations in induction threshold and expression magnitude of long-term potentiation and long-term depression at hippocampal synapses. Hippocampus. 2010; 22(2):188-99. DOI: 10.1002/hipo.20881. View

14.

Woolley C, Gould E, McEwen B . Exposure to excess glucocorticoids alters dendritic morphology of adult hippocampal pyramidal neurons. Brain Res. 1990; 531(1-2):225-31. DOI: 10.1016/0006-8993(90)90778-a. View

15.

Kemp M, Roberts P, Pook P, Jane D, Jones A, Jones P . Antagonism of presynaptically mediated depressant responses and cyclic AMP-coupled metabotropic glutamate receptors. Eur J Pharmacol. 1994; 266(2):187-92. DOI: 10.1016/0922-4106(94)90109-0. View

16.

Hashimoto K, Sawa A, Iyo M . Increased levels of glutamate in brains from patients with mood disorders. Biol Psychiatry. 2007; 62(11):1310-6. DOI: 10.1016/j.biopsych.2007.03.017. View

17.

Vogel S, Klumpers F, Kroes M, Oplaat K, Krugers H, Oitzl M . A Stress-Induced Shift From Trace to Delay Conditioning Depends on the Mineralocorticoid Receptor. Biol Psychiatry. 2015; 78(12):830-9. DOI: 10.1016/j.biopsych.2015.02.014. View

18.

Greenough W, Klintsova A, Irwin S, Galvez R, Bates K, Weiler I . Synaptic regulation of protein synthesis and the fragile X protein. Proc Natl Acad Sci U S A. 2001; 98(13):7101-6. PMC: 34629. DOI: 10.1073/pnas.141145998. View

19.

Monte-Silva K, Kuo M, Hessenthaler S, Fresnoza S, Liebetanz D, Paulus W . Induction of late LTP-like plasticity in the human motor cortex by repeated non-invasive brain stimulation. Brain Stimul. 2012; 6(3):424-32. DOI: 10.1016/j.brs.2012.04.011. View

20.

Steuwe C, Daniels J, Frewen P, Densmore M, Theberge J, Lanius R . Effect of direct eye contact in women with PTSD related to interpersonal trauma: Psychophysiological interaction analysis of connectivity of an innate alarm system. Psychiatry Res. 2015; 232(2):162-7. DOI: 10.1016/j.pscychresns.2015.02.010. View