GABABR-dependent long-term depression at hippocampal synapses between CB1-positive interneurons and CA1 pyramidal cells
We used hippocampal slices (300 μm) which were prepared from the brains of 14–21 day-old WT (C57Bl6) mice. CA1 pyramidal cells were identified visually using IR-video microscopy. In paired recordings, presynaptic CB1+ putative basket cells were identified by location and firing pattern. The identity of the presynaptic neuron was further confirmed after finding the connected postsynaptic cell, by asynchronous release evoked by high frequency stimulation (10 action potentials 50 Hz) and the presence of depolarization induced suppression of inhibition. To extracellularly evoke synaptic currents, glass electrodes filled with ACSF were placed in the stratum pyramidale within ∼50–100 μm of the body of the recorded neuron. The theta burst stimulation protocol consisted of four bursts of five stimuli at 50 Hz separated by 200 ms. For LTD induction TBS was repeated 25 times.
For statistical analysis, the paired Student’s t-test was used, and data are presented as mean ± SD.
According to the results of our data we found that TBS triggers robust LTD at CB1+ interneuron to pyramidal cell connections. The LTD induction is postsynaptic and requires activation of GABAB receptors. Also, we show that LTD at this connection involves GABABR-dependent suppression of adenylyl cyclase and consequent reduction of PKA activity. This contrasts markedly with other hippocampal synapses, where TBS typically induces LTP. Thus, functionally TBS-like activity will selectively suppresses CB1+ synapses and simultaneously promote other GABAergic inputs, which can have a strong modulatory impact on hippocampal network activity patterns.