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Cited by 240Neuroscience and Neuropharmacology ResearchNeurotransmitter Receptor Influence on BehaviorTreatment of Major Depression

Synaptic plasticity and mental health: methods, challenges and opportunities

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Appelbaum, Lawrence G., Shenasa, Mohammad Ali, Stolz, Louise, Daskalakis, Zafiris·2023·Neuropsychopharmacology
DOI 10.1038/s41386-022-01370-wPMC PMC9700665
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Abstract

Activity-dependent synaptic plasticity is a ubiquitous property of the nervous system that allows neurons to communicate and change their connections as a function of past experiences. Through reweighting of synaptic strengths, the nervous system can remodel itself, giving rise to durable memories that create the biological basis for mental function. In healthy individuals, synaptic plasticity undergoes characteristic developmental and aging trajectories. Dysfunctional plasticity, in turn, underlies a wide spectrum of neuropsychiatric disorders including depression, schizophrenia, addiction, and posttraumatic stress disorder. From a mechanistic standpoint, synaptic plasticity spans the gamut of spatial and temporal scales, from microseconds to the lifespan, from microns to the entire nervous system. With the numbers and strengths of synapses changing on such wide scales, there is an important need to develop measurement techniques with complimentary sensitivities and a growing number of approaches are now being harnessed for this purpose. Through hemodynamic measures, structural and tracer imaging, and noninvasive neuromodulation, it is possible to image structural and functional changes that underlie synaptic plasticity and associated behavioral learning. Here we review the mechanisms of neural plasticity and the historical and future trends in techniques that allow imaging of synaptic changes that accompany psychiatric disorders, highlighting emerging therapeutics and the challenges and opportunities accompanying this burgeoning area of study.

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  • At the molecular level, synaptic plasticity processes are supported by glutamatergic signaling through NMDA and AMPA receptors, neurotrophins such as BDNF, intracellular signaling cascades, and dynamic interactions with astrocytes and microglia.

    “At the molecular level, these processes are supported by glutamatergic signaling through N-Methyl-D-aspartic acid (NMDA) and α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, neurotrophins such as brain-derived neurotrophic factor (BDNF), intracellular signaling cascades, and dynamic interactions with astrocytes and microglia [82, 83].”

    From Toward a Unified Framework in Molecular Neurobiology of Alzheimer’s Disease: Revisiting the Pathophysiological Hypotheses (2026) · cites this paper as [83]

    The “Mechanisms of neural plasticity” section identifies NMDA and AMPA receptors as mechanisms of synaptic plasticity. “Mechanistic roles behind changes in neural plasticity and clinical improvement” describes molecular signaling pathways and BDNF’s role in plasticity. Our copy does not describe the claimed dynamic interactions with astrocytes and microglia; searches for both terms found no matching passage. Page numbers were not available. (LLM, conf=0.87)

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Authors
Appelbaum, L. G., Shenasa, M. A., Stolz, L., & Daskalakis, Z.
Affiliations
University of California San Diego (US)
Corresponding author
Appelbaum, Lawrence G.
ORCID
Venue
Neuropsychopharmacology
Publisher
Springer Science and Business Media LLC
Published
2022-07-09
Volume
48
Issue
1
Pages
113-120
ISSN
  • 0893-133X (ISSN-L)
  • 1740-634X
DOI
10.1038/s41386-022-01370-w
PMC
PMC9700665
OpenAlex
W4284987998
Cited by
240
References
16
Citations by year
2026: 72 · 2025: 87 · 2024: 55 · 2023: 23 · 2022: 3
FWCI
6.06
Type
journal article
Language
en
Open access
Licence
Locations
  • Neuropsychopharmacology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
Support was generously provided by the Kreutzkamp gift to UCSD to support the authors time in preparing this manuscript
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Keywords
synaptic plasticity, mental health, neuropsychiatric disorders, depression, schizophrenia, addiction, post-traumatic stress disorder, synaptic imaging, structural imaging, non-invasive neuromodulation, synaptic remodeling, memory
MeSH terms
Humans, Learning, Mental Health, Neuronal Plasticity, Neurons, Synapses

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