Glutamate-independent long-term depression in rat hippocampus by activation of GABA(A) receptors

Long-term depression (LTD) of synaptic transmission is a candidate for a neuronal model of forgetting and is considered to be important in learning and memory. The present studyemployed extracellular recording in the CA1 pyramidal cell layer of rat hippocampal slices following orthodromic stimulation of Schaffer collateral fibres in stratum radiatum. Muscimol induced a time and concentration-dependent LTD at a frequency of stimulation of 0.01 Hz or in the absence of stimulation. The LTD was reversed by stimulation at 1 Hz. The ability of muscimol to act via GAB(A), receptors was confirmed by the ability of bicuculline (5 mu M) to reverse the LTD. The NMDA receptor antagonist 2-AP5, the selective metabotropic antagonist L(+)-AP3 and the non-selective glutamate antagonists kynurenate, failed to modify the LTD. (1S,3R)-ACPD, a selective agonist at metabotropic receptors, did not induce LTD. The lack of involvement of glutamate receptors in muscimol induced LTD in our protocol may indicate a novel type of long-lasting synaptic depression.