AMPA RECEPTOR DESENSITIZATION PROVIDES A MECHANISM FOR GAIN CONTROL IN THE DORSAL LATERAL GENICULATE NUCLEUS

Neural gain control determines how sensory, motor, associative, and cognitive information is represented in the brain. One mechanism underlying neuronal gain are the filter properties of the synapses in which the information is processed. It has been shown that synaptic short-term plasticity (STP) can be influenced by AMPA receptor (AMPAR) desensitization. We therefore hypothesize that desensitization controls gain and tuning properties of neurons. To test this hypothesis, we focused on the visual system and analyzed the role of desensitization (AMPAR) in information processing in dLGN relay cells (RCs). To this end, we generated a computational model of (RCs). Response tuning curves were left-shifted and maximal firing rates increased in a model neuron with AMPARs that recover instantaneously from desensitization. Results from the simulations suggested that AMPAR desensitization decreases not only response but also input gain of dLGN RCs. To test this prediction, we recorded in vivo responses of RCs in a mouse model in which recovery from desensitization of AMPARs is faster than in wildtype mice. Consistent with the data from simulations, we observed that a faster recovery from desensitization leads to a left shift in the contrast tuning curve, increased saturation at lower contrasts, and increased steepness in moving grating tuning curves. In addition, firing rate to the non-preferred stimulus increases in RCs with faster recovery from desensitization. Altogether, we show that desensitization of AMPARs decreases input and response gain, reduces the risk of response saturation and increases the signal-to-noise ratio.