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Related Concept Videos

Long-term Potentiation01:25

Long-term Potentiation

Long-term potentiation, or LTP, is one of the ways by which synaptic plasticity—changes in the strength of chemical synapses—can occur in the brain. LTP is the process of synaptic strengthening that occurs over time between pre and postsynaptic neuronal connections. The synaptic strengthening of LTP works in opposition to the synaptic weakening of long-term depression (LTD) and together are the main mechanisms that underlie learning and memory.
Hebbian LTP
LTP can occur when presynaptic neurons...
Long-term Potentiation01:35

Long-term Potentiation

Long-term potentiation, or LTP, is one of the ways by which synaptic plasticity—changes in the strength of chemical synapses—can occur in the brain. LTP is the process of synaptic strengthening that occurs over time between pre- and postsynaptic neuronal connections. The synaptic strengthening of LTP works in opposition to the synaptic weakening of long-term depression (LTD) and together are the main mechanisms that underlie learning and memory.
Long-term Depression01:05

Long-term Depression

Long-term depression, or LTD, is one of the ways by which synaptic plasticity—changes in the strength of chemical synapses—can occur in the brain. LTD is the process of synaptic weakening that occurs over time between pre and postsynaptic neuronal connections. The synaptic weakening of LTD works in opposition to synaptic strengthening by long-term potentiation (LTP) and together are the main mechanisms that underlie learning and memory.
Long-term Depression01:03

Long-term Depression

Long-term depression, or LTD, is one of the ways by which synaptic plasticity—changes in the strength of chemical synapses—can occur in the brain. LTD is the process of synaptic weakening that occurs over time between pre and postsynaptic neuronal connections. The synaptic weakening of LTD works in opposition to synaptic strengthening by long-term potentiation (LTP) and together are the main mechanisms that underlie learning and memory.
Calcium Ion Concentration Mechanism
If over time, all...
Neuroplasticity01:01

Neuroplasticity

Neuroplasticity reflects the brain's remarkable capacity to adapt and evolve, responding dynamically to learning, experiences, or injury by reorganizing its neural circuitry. This reorganization involves creating new neural connections and refining old ones through a series of biological processes that contribute to the brain's lifelong development and adaptability.
Chemical Synapses01:26

Chemical Synapses

Chemical synapses are specialized sites between two neurons or between a neuron and a non-neuronal cell like a muscle, glandular or sensory cell.
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...

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Updated: Jun 27, 2026

DetectSyn: A Rapid, Unbiased Fluorescent Method to Detect Changes in Synapse Density
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DetectSyn: A Rapid, Unbiased Fluorescent Method to Detect Changes in Synapse Density

Published on: July 22, 2022

Synaptic Plasticity-Intrinsic Excitability and Antidepressant Discovery.

Masaru Tanaka1

  • 1HUN-REN-SZTE Neuroscience Research Group, Danube Neuroscience Research Laboratory, Hungarian Research Network, University of Szeged (HUN-REN-SZTE), 6725 Szeged, Hungary.

Biomedicines
|June 26, 2026
PubMed
Summary

Antidepressant efficacy relies on stabilizing brain circuits through synaptic plasticity and intrinsic excitability. A new Induction-Consolidation-Maintenance framework guides discovery for better depression treatments.

Keywords:
antidepressive agentsesketamineexcitatory postsynaptic potentialsketaminemajor depressive disorder (MDD)neurogenesisneuronal excitabilitysignal transductionsynaptic plasticityα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors

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Evaluation of Synaptic Multiplicity Using Whole-cell Patch-clamp Electrophysiology

Published on: April 23, 2019

Area of Science:

  • Neuroscience
  • Pharmacology
  • Psychiatry

Background:

  • Major depressive disorder (MDD) is a leading cause of disability with limited relief from traditional monoamine-based antidepressants.
  • Rapid-acting antidepressants show promise by linking symptom improvement to glutamatergic plasticity, but durable effects require circuit stabilization.
  • Understanding the mechanisms of circuit stabilization is crucial for developing more effective and lasting antidepressant therapies.

Purpose of the Study:

  • To synthesize evidence on the roles of synaptic plasticity and intrinsic excitability in antidepressant efficacy.
  • To propose an integrated framework, the Induction-Consolidation-Maintenance (ICM) model, for guiding future antidepressant discovery.
  • To link specific phases of neural circuit modulation to therapeutic windows and relapse prevention.

Main Methods:

  • Review of existing scientific literature on synaptic plasticity and intrinsic excitability in antidepressant action.
  • Analysis of molecular and cellular mechanisms involved in the induction and consolidation of synaptic changes.
  • Examination of the role of ion channels in regulating neuronal excitability and network stability.

Main Results:

  • Antidepressant efficacy involves coordinated synaptic plasticity (induction via NMDARs/AMPARs, consolidation via TrkB/eEF2K/SV2A) and intrinsic excitability (Kv7, HCN, GIRK channels).
  • These processes transform transient potentiation into persistent network changes, crucial for sustained therapeutic benefit.
  • The ICM framework integrates these phases, suggesting distinct therapeutic windows and biomarker applications.

Conclusions:

  • A phase-specific model (ICM) integrating synaptic plasticity and intrinsic excitability provides a roadmap for novel antidepressant development.
  • This framework highlights the importance of circuit stabilization for durable antidepressant effects.
  • Biomarkers like SV2A PET, EEG, and fMRI are discussed as potential tools, though validation for treatment guidance is pending.