Denervated mouse dentate granule cells adjust their excitatory but not inhibitory synapses following in vitro entorhinal cortex lesion

Abstract

Neurons adjust their synaptic strength in a homeostatic manner following changes in network activity and connectivity. While this form of plasticity has been studied in detail for excitatory synapses, homeostatic plasticity of inhibitory synapses remains not well-understood. In the present study, we employed entorhinal cortex lesion (ECL) of organotypic entorhino-hippocampal tissue cultures to test for homeostatic changes in GABAergic neurotransmission onto partially denervated dentate granule cells. Using single and paired whole-cell patch-clamp recordings, as well as immunostainings for synaptic markers, we find that excitatory synaptic strength is robustly increased 3 days post lesion (dpl), whereas GABAergic neurotransmission is not changed after denervation. Even under conditions of pharmacological inhibition of glutamatergic neurotransmission, which prevents neurons to compensate for the loss of input via excitatory synaptic scaling, down-scaling of GABAergic synapses does not emerge 3 days after denervation. We conclude that granule cells maintain structural and functional properties of GABAergic synapses even in the face of substantial changes in network connectivity. Hence, alterations in inhibitory neurotransmission, as seen in pathological brain states, may not simply reflect a homeostatic response to disconnection.