Related Experiment Video
Updated: Jul 6, 2026
10:34
A High-content Assay for Monitoring AMPA Receptor Trafficking
Published on: January 28, 2019
An essential role for PICK1 in NMDA receptor-dependent bidirectional synaptic plasticity
Akira Terashima1, Kenneth A Pelkey, Jong-Cheol Rah
1Developmental Synaptic Plasticity Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 35 Convent Drive, Bethesda, MD 20892, USA.
Neuron
|March 28, 2008
Summary
The protein PICK1 is crucial for both long-term potentiation (LTP) and long-term depression (LTD) in the hippocampus. It regulates synaptic plasticity by interacting with AMPA receptors (AMPARs) and NMDA receptors (NMDARs).
Area of Science:
- Neuroscience
- Molecular Biology
- Synaptic Plasticity
Background:
- PICK1 (Protein Interacting with C Kinase 1) is a calcium-sensing protein with PDZ domains.
- It interacts with AMPA receptor (AMPAR) subunits GluR2 and GluR3, influencing their trafficking.
- PICK1 has been primarily linked to long-term depression (LTD).
Purpose of the Study:
- To investigate the role of PICK1 in both NMDA receptor (NMDAR)-dependent long-term potentiation (LTP) and LTD in the hippocampus.
- To determine if PICK1 is involved in mechanisms underlying synaptic plasticity.
Main Methods:
- Electrophysiological recordings in hippocampal CA1 pyramidal neurons.
- Manipulating PICK1 activity through overexpression and blockade of its PDZ interactions.
- Genetic deletion of PICK1.
Main Results:
- PICK1 overexpression potentiates AMPAR-mediated transmission in an NMDAR-dependent manner, occluding LTP.
- Blocking PICK1 PDZ interactions or deleting PICK1 inhibits LTP.
- Deletion of PICK1 or blockade of its PDZ binding prevents NMDAR-dependent LTD.
Conclusions:
- PICK1 plays a critical role in hippocampal NMDAR-dependent LTP.
- PICK1 is essential for bidirectional NMDAR-dependent long-term synaptic plasticity, including both LTP and LTD.
Related Concept Videos
01:35Long-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.
01:25Long-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...
Hebbian LTP
LTP can occur when presynaptic neurons...
01:30Ligand-Gated Ion Channel Receptor: Gating Mechanism
Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
01:23Role of Neurotransmitters in Memory
Neurotransmitters are integral to the brain's communication system, enabling neurons to transmit signals across synapses. This chemical exchange underpins various cognitive functions, including memory processes. The role of neurotransmitters in memory is multifaceted, influencing the encoding, consolidation, and retrieval of memories through their action on different neural circuits.
Glutamate and Synaptic Plasticity
Glutamate, the brain's main excitatory neurotransmitter, is critical for...
Glutamate and Synaptic Plasticity
Glutamate, the brain's main excitatory neurotransmitter, is critical for...
01:03Long-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...
Calcium Ion Concentration Mechanism
If over time, all...
01:05Long-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.