Contributions of Receptor Desensitization and Saturation to Plasticity at the Retinogeniculate Synapse

Abstract

The retinogeniculate synapse conveys visual information from the retina to thalamic relay neurons. Here, we examine the mechanisms of short-term plasticity that can influence transmission at this connection in mouse brain slices. Our studies show that synaptic strength is modified by physiological activity patterns due to marked depression at high frequencies. Postsynaptic mechanisms of plasticity make prominent contributions to this synaptic depression. During trains of retinal input stimulation, receptor desensitization attenuates the AMPA EPSC while the NMDA EPSC saturates. This differential plasticity may help explain the distinct roles of these receptors in shaping the relay neuron response to visual stimulation with the AMPA component being important for transient responses, while sustained high frequency responses rely more on the NMDA component.

Paired-pulse depression of unitary quantal amplitude at single hippocampal synapses

“…5). This enlarges the set of possible mechanisms for PPD, which already includes conduction failure (15), Ca 2ϩ channel failure (3), release site refractoriness (8), decreased P r (5,16,36), and postsynaptic desensitization (4,36).…”

“…Paired-pulse facilitation (PPF) is generally explained as an increase of release probability (P r ) during the second stimulus, arising from prior accumulation of residual Ca 2ϩ near active zones or a lingering effect of Ca 2ϩ on a Ca 2ϩ sensor (1,2). In contrast, paired-pulse depression (PPD) comes in multiple forms (3) and is open to a much wider range of possible explanations: receptor desensitization can be important in some cases (4) but is in general excluded. Instead, PPD is thought to originate presynaptically in most systems, as reflected by decreased transmitter output (5,6).…”

Short-Term Presynaptic Plasticity

“…Low-affinity AMPA receptor antagonists, such as g-D-glutamylglycine or kynurenate, can minimize the extent of saturation of these receptors Wadiche and Jahr 2001). Postsynaptic receptors can also desensitize, making them unavailable for subsequent activation, and leading to short-term decreases in synaptic responses (Trussell et al 1993;Chen et al 2002;Xu-Friedman and Regehr 2004). It is possible to prevent AMPA receptor desensitization pharmacologically (Francotte et al 2006), but it may not be possible to prevent desensitization of other types of receptors.…”

Short-Term Depression in Thalamocortical Synapses of Cat Primary Visual Cortex

“…Rapidly saturating depression at other synapses Rapidly saturating depression, in which a dramatic drop in EPSP amplitude after the first release event is followed by little additional depression, has been described in vitro at both excitatory and inhibitory synapses, including the calyx of Held (Brenowitz and Trussell, 2001), retinogeniculate synapses (Chen et al, 2002), neocortical synapses (Galarreta and Hestrin, 1998), climbing fiber synapses onto cerebellar Purkinje cells (Dittman et al, 2000), inhibitory synapses in the hippocampus (Kraushaar and Jonas, 2000), and cerebellar corticonuclear synapses (Telgkamp and Raman, 2002). In many cases, these synapses have been shown to have morphological and physiological specializations that distinguish them from typical central synapses.…”