AMPA Glutamate Receptor (AMPA Receptor), Conductance Models

Definition

A glutamate receptor that is permeable to sodium ions and carries an excitatory synaptic current following the binding of glutamate. AMPA receptors are regulated to control the maximum synaptic current by processes of synaptic plasticity and they co-localize with NMDA receptors.

Detailed Description

AMPA receptors are named for the selective agonist (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) that does not bind well to other glutamate receptors. The receptor is permeable to cations and can allow Na⁺, K⁺, and Ca²⁺ to cross the membrane and has an equilibrium potential E_AMPA = 0 mV. The permeability to Ca²⁺ is small and is not considered important for initiating signaling cascades. AMPA receptors are composed of four types of subunits, and the combination of subunits determines the kinetics and permeability to cations.

Kinetics of AMPA Receptors

Mathematical representations of AMPA currents include the time-dependent synaptic conductance, g_AMPA(t), in the current–voltage equation:

$$ {I}_{AMPA}(t)={g}_{AMPA}(t)\left(V(t)-{E}_{AMPA}\right) $$

(1)

The time-dependent synaptic conductance represents the opening and closing kinetics of the receptor channels and may be based on a double exponential function (or a similarly shaped function).

$$ {g}_s(t)={\overline{g}}_s\left({e}^{-t/{\tau}_1}-{e}^{-t/{\tau}_2}\right) $$

(2)

where τ₁ is the onset time constant (τ₂ < 0.1 ms) and τ₂ is the decay time constant (τ₂ < 3 ms) (Hestrin et al. 1990; Trussell et al. 1993; Jonas et al. 1993). AMPA currents have a faster decay than NMDA currents (Jonas and Spruston 1994) and typically have a substantially larger peak current.

Because AMPA currents are usually the dominant excitatory synaptic currents, simple representations of these currents may be the only synaptic currents included in the practice of modeling neural circuits. In models with low time resolution, AMPA currents may be represented as increased currents in a single time bin without short-term temporal details. However, these simple models may contain long-term plasticity that changes the circuit dynamics over time by changing the strength of connections between neurons.

Computational Functions of AMPA Receptors

The excitatory characteristics of AMPA currents can be the main driver of activity in a network of neurons and for communication across long distances such as from the periphery to the central nervous system. Due to the short time constants of AMPA kinetics, signal transmission can carry high temporal precision. An example of this precision is found in the auditory pathway where the interaural time difference can be discerned to extreme precision (Konishi 1990).

Another consequence of the short duration of AMPA currents is that they require a large population of independent asynchronous inputs to deliver a constant depolarization to a neuron. A single AMPA synapse can deliver a fast synaptic current that is filtered by cable properties of the dendrite where the postsynaptic terminal is located (Rall 1967). But there are temporal limitations to how much filtering is possible to deliver the excitatory effect to the spike-generating zone of the postsynaptic neuron. Multiple AMPA currents located on the postsynaptic neurons can overcome this constraint if the rate of incoming spikes is high enough and well distributed in time to overlap. Thus, the synaptic dynamics of a single synaptic terminal may not have a great influence on the postsynaptic activity.

The strength of the synaptic current is not the only determinant of the efficacy of the synaptic input to generate a spike in the postsynaptic neuron. Spikes are triggered by changes in membrane potential, and the filtering properties of the neuron are critical in how the dynamics of the individual synapses are transformed into changes in postsynaptic activity.

AMPA Synaptic Dynamics

In addition to the channel kinetics, AMPA currents exhibit short-term plasticity that can result from both pre- and postsynaptic mechanisms (Zucker and Regehr 2002; Blitz et al. 2004). Presynaptic mechanisms affect the release of glutamate and can influence the peak of the current on subsequent presynaptic spikes. Postsynaptic mechanisms affect the response of AMPA receptors to the concentration of glutamate in the synaptic cleft.

AMPA currents are also involved in long-term plasticity and can be the main component of changes in synaptic strength. AMPA currents do not play a direct role in inducing long-term plasticity but reflect the changes in presynaptic release and their own response to glutamate caused by other mechanisms.

Cross-References

• Kinetic Models of Postsynaptic Currents

• N-Methyl-D-Aspartate (NMDA) Receptors, Conductance Models