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Event: 1944

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

Synaptic dysfunction

Short name
The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. More help
Dysfunctional synapses
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Biological Context

Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE. More help
Level of Biological Organization
Organ

Organ term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place.  For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable.  For individual/population events, the organ context is not applicable.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help
Organ term
principal neuronal circuit

Key Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; https://aopwiki.org/info_pages/2/info_linked_pages/7#List). Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling).  The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor).  Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description.  To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons.  If a desired term does not exist, a new term request may be made via Term Requests.  Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help
Process Object Action
decreased neurotransmitter release CNS neuron (sensu Vertebrata) decreased
increased synaptic depression CNS neuron (sensu Vertebrata) increased

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE.Clicking on the name of the AOP will bring you to the individual page for that AOP. More help
AOP Name Role of event in AOP Point of Contact Author Status OECD Status
tau-AOP KeyEvent Erwin L Roggen (send email) Under development: Not open for comment. Do not cite
IGR binding leads to impairment of learning and memory (via loss of drebrin) KeyEvent Shihori Tanabe (send email) Under development: Not open for comment. Do not cite Under Development
Neuron defect induced early behavioral change KeyEvent Woo-Keun Kim (send email) Under development: Not open for comment. Do not cite

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help
Term Scientific Term Evidence Link
Human, rat, mouse Human, rat, mouse High NCBI

Life Stages

An indication of the the relevant life stage(s) for this KE. More help
Life stage Evidence
All life stages High

Sex Applicability

An indication of the the relevant sex for this KE. More help
Term Evidence
Unspecific High

Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. More help

Synaptic dysfunction refers to the impairment or disruption of communication between neurons at synapses. It occurs when neurotransmitter release, receptor function, or synaptic structure is altered or damaged, leading to impaired signaling. Such dysfunction can contribute to various neurological and psychiatric conditions, including Alzheimer's disease, Parkinson's disease, depression, schizophrenia, and autism spectrum disorders. 

How It Is Measured or Detected

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help
  • Electrophysiology (Patch Clamp, Field Potential Recording): Measures neurotransmition efficiency and receptor function by currents recordings. Evaluate synaptic plasticity, such as LTP and LTD
  • Microdialysis or HPLC (High-Performance Liquid Chromatography): Quantifies neurotransmitter levels directly.
  • Western Blot, ELISA: Evaluate proteins expression.
  • Immunohistochemistry and imagings : Evaluate expression and locarization for pre- and post synaptic proteins, mitochondrial imaging, infkammation and immune responses using microscopies.
  • Behavioral Tests (e.g., Morris Water Maze, Novel Object Recognition): Evaluate cognitive functions related to synaptic plasticity.
  • Morphlogical changes: Electron Microscopy (EM): Visualize synaptic ultrastructure. Confocal or Two-photon Microscopy: Observe dendritic spine morphology and density changes. Golgi Staining: Analyze dendritic spine density and morphology.
  • MRI, PET EEG

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided).  More help

Species applicability includes humans, using clinical assessments like neuroimaging, EEG, and cognitive tests; animal models (e.g., rodents) employing electrophysiological, behavioral, and biochemical assays; and cultured neuronal cells for molecular-level studies. Life-stage applicability covers developmental stages for neurodevelopmental disorders, adulthood for psychiatric and neurodegenerative diseases, and elderly populations for age-related cognitive decline. Experimental system applicability spans in vitro models for cellular mechanisms, ex vivo brain slices for electrophysiological studies, and in vivo animal models for behavioral and systemic analysis. Disease applicability involves neurological and psychiatric conditions such as Alzheimer's, Parkinson's, schizophrenia, depression, epilepsy, and autism spectrum disorders. Clearly defining these domains ensures accurate interpretation, facilitates translational research, and supports targeted therapeutic development for various neurological and psychiatric disorders.

References

List of the literature that was cited for this KE description. More help

Jocelyn R Barnes , Bandhan Mukherjee , Ben C Rogers , Firoozeh Nafar , Madeline Gosse , Matthew P Parsons.,The Relationship Between Glutamate Dynamics and Activity-Dependent Synaptic Plasticity. J Neurosci. 2020 Apr 1;40(14):2793-2807.