Lack of AMPA receptor desensitization during basal synaptic transmission in the hippocampal slice

Excitatory postsynaptic currents in the CA1 region of rat hippocampal slice s are mediated primarily by alpha-amino-3-hydroxy-5-methyl-3-isoxazolepropi onic acid (AMPA) receptors in response to synaptically released glutamate. Outside-out patches from pyramidal cells in this region have shown that AMP A receptors are desensitized by short (1 ms) pulses of glutamate. We have t aken a number of approaches to ask whether synaptic receptors desensitize i n response to synaptically released glutamate in the slice. Recordings with paired pulses and minimal stimulation conditions that are presumably activ ating only a single release site do not show evidence for desensitization. Furthermore, cyclothiazide, a drug that blocks desensitization, does not al ter paired-pulse ratios even under conditions of high probability of releas e, which should maximize desensitization. These results suggest that synapt ic receptors do not desensitize in response to synaptically released glutam ate during basal synaptic transmission.