Adenylate cyclase 1 promotes strengthening and experience-dependent plasticity of whisker relay synapses in the thalamus

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Non-technical summaryCyclic AMP-mediated signalling plays an important role in the development and plasticity of synaptic circuits, and adenylate cyclase 1 is a major enzyme for cyclic AMP production in the brain of newborns. We show that in mice deficient in adenylate cyclase 1, developmental strengthening and experience-dependent plasticity of excitatory synapses are impaired, but developmental pruning of the synapses is not affected. These results increase our understanding of the processes by which neuronal circuits are formed and modified during development.Synaptic refinement, a process that involves elimination and strengthening of immature synapses, is critical for the development of neural circuits and behaviour. The present study investigates the role of adenylate cyclase 1 (AC1) in developmental refinement of excitatory synapses in the thalamus at the single-cell level. In the mouse, thalamic relay synapses of the lemniscal pathway undergo extensive remodelling during the second week after birth, and AC1 is highly expressed in both pre- and postsynaptic neurons during this period. Synaptic connectivity was analysed by patch-clamp recording in acute slices obtained from mice carrying a targeted null mutation of the adenylate cyclase 1 gene (AC1-KO) and wild-type littermates. We found that deletion of AC1 had no effect on the number of relay inputs received by thalamic neurons during development. In contrast, there was a selective reduction of AMPA-receptor-mediated synaptic responses in mutant thalamic neurons, and the effect increased with age. Furthermore, experience-dependent plasticity was impaired in thalamic neurons of AC1-KO mice. Whisker deprivation during early life altered the number and properties of relay inputs received by thalamic neurons in wild-type mice, but had no effects in AC1-KO mice. Our findings underline a role for AC1 in experience-dependent plasticity of excitatory synapses.

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