Prevention of muscimol-induced long-term depression by brain-derived neurotrophic factor

1. The authors have recently reported a new protocol for inducing long-term depression through activation of GABA(A) receptors in the hippocampal slic es. This long-term depression is reversed by bicuculline and potentiated by neurosteroids such as alphaxalone. It was also shown that glutamate recept or activity is not involved in the induction of this novel type of long-ter m depression. Brain derived neurotrophic factor is a member of the neurotro phins family widely expressed in the central nervous system. There is incre asing evidence that indicate an important role for brain-derived neurotroph ic factor in synaptic plasticity. It has been reported that brain-derived n eurotrophic factor level is downregulated by GABA system. The present study investigated a possible relation between muscimol-induced long-term depres sion and brain-derived neurotrophic factor level. 2. Extracellular recordings were made in the CA1 pyramidal cell layer of ra t hippocampal slices following orthodromic stimulation of Schaffer collater al fibers in stratum radiatum. 3. It was observed that brain-derived neurotrophic factor at concentration that did not have any effect itself on the population spike, prevents the i nduction of long-term depression by muscimol. In addition to this, K-252a a n inhibitor of Trk type kinase blocked the prevention of muscimol-induced L TD by brain-derived neurotrophic factor. 4. The results suggest that there is an interaction between muscimol-induce d long-term depression and brain-derived neurotrophic factor and may explai n the post receptor mechanism of muscimol-induced long-term depression thro ugh a bilateral relation between GABA(A) activity and brain-derived neurotr ophic factor.