Providing straightforward information pertaining to drugs, drug use & drug policy. The Grey Pages promotes drug-related literacy and advocates a system of viable and tolerant drug policies. This is my personal collection of commentaries, essays, tid-bits, and other such writings on everything ranging from drug use, drug policy and drug-myths, to drug-science, addiction, human behavior, and the workings of the human brain. I started this blog with a particular focus on opioids, and over the past year have found my interest gravitate toward the intriguing, ever-changing world of designer intoxicants (i.e. "research chemicals" or "designer drugs").

Friday, April 6, 2012

Archive Addition: The NMDA Complex

What is the NMDA Receptor/Channel Complex? 

Ionotropic NMDAR: The NMDA receptor (or NMDAR) is a type of glutamatergic receptor and is named after one of its endogenous ligands, N-methyl-D-aspartate. Though this ligand is not the most significant neurotransmitter for NMDA receptor function, it binds selectively to NMDA sites and does not affect other glutamate receptors.

NMDAR Complex: NMDA receptors are but one part of a cellular device referred to as the NMDA receptor/channel complex. The NMDA complex consists of a ligand gated ion channel (which plays the role of a gate), in addition to ionotropic binding sites on the exterior surface of the cell, which act to modulate the function of the gate. If the neural pathways of the CNS are to be perceived as roads and highways, the NMDA complex works as a traffic light of sorts, which is tasked with regulating the flow of traffic through the intersections (synapses). In order to facilitate traffic flow (i.e. neurotransmission) between nerve cells, the NMDA ion channel must remain in an open position.

The NMDA complex has seven distinct binding sites, located on the exterior surface of the cell - most notable are the glutamate and glycine sites, which must be occupied by glutamate and glycine in order for the interior ion channel to remain opened (or in order for the "traffic light to be green"); the other sites are magnesium ion, zinc ion, the PCP1 site, polyamine site, and phosphorylation site.

Function of the NMDAR: 

Ligand gated ion channels are located on post synaptic sites of excitatory neurons. In order for excitatory signals to flow freely, the ligand gated channel must be open. In order for the gate to be open, the NMDA receptors must be activated - both glutamate and glycine act as co-agonists to activate the NMDAR. Both of these ligands must be bound with the NMDAR in order for the gate to remain opened, for signals to flow freely.

In laymans terms; the NMDA modulates the efficacy of synaptic connections between excitatory neurons. The NMDA Complex is to neural networks as the traffic light is to road networks.

When NMDA receptors are present in greater relative abundance, the strength of a particular connection is increased. This is but one mechanism contributing to synaptic plasticity (see below) - i.e. a gradual adaptation or fluctuation in the overall strength or activity level of a particular synaptic connection. 

NMDA Complex & Synaptic Plasticity: 

The NMDA complex plays a primary role in mediating synaptic plasticity - a process by which the efficacy of certain synapsing neuro-pathways increases over time, mediating the complex interneural connections (via synaptic intersections) which are strengthened over time to facilitate crucial adaptive processes of the central nervous system. Some primary examples are as follows: 

learning - certain complex pathways are established and potentiated (i.e. enhanced) in order to make the connections required for storing and effectively utilizing learned information.

memory formation & memory recollection - connections are made between sensory or environmental processing areas and cortical storage areas.

sensory-cortical connections - emotions, feelings or memories which are invoked by certain tastes or smells.

behavioral reinforcement and addiction - a complex phenomenon requiring the development of connections involving instinct, memory, and learning.

Some Interesting Offsite Reading:

Research Paper on the function of NMDAR (K Zito & V Scheuss)

More on Synaptic Plasticity (Neuroscience Online - University of TX)

Emerging Role of NMDA Antagonists in Analgesia (Medscape - Various Authors)

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