Spatial regulation of coordinated excitatory and inhibitory synaptic plasticity at dendritic synapses

• Published in: Cell reports (Cambridge) Vol. 38; no. 6; p. 110347
• Main Authors: Ravasenga, Tiziana, Ruben, Massimo, Regio, Vincenzo, Polenghi, Alice, Petrini, Enrica Maria, Barberis, Andrea
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 08.02.2022; Cell Press; Elsevier
• Subjects: Animals; CA1 Region, Hippocampal - physiology; calcium imaging; dendrites; Dendrites - physiology; GABA uncaging; GABAergic synaptic plasticity; gephyrin; glutamate uncaging; glutamatergic spines; glutamatergic synaptic plasticity; heterosynaptic plasticity; Long-Term Potentiation - physiology; Mice; Neuronal Plasticity - physiology; Neurons - physiology; receptor lateral diffusion; Synapses - physiology; GABA uncaging; glutamatergic spines; heterosynaptic plasticity; glutamatergic synaptic plasticity; receptor lateral diffusion; dendrites; glutamate uncaging; gephyrin; calcium imaging; GABAergic synaptic plasticity
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2022.110347

The induction of synaptic plasticity at an individual dendritic glutamatergic spine can affect neighboring spines. This local modulation generates dendritic plasticity microdomains believed to expand the neuronal computational capacity. Here, we investigate whether local modulation of plasticity can also occur between glutamatergic synapses and adjacent GABAergic synapses. We find that the induction of long-term potentiation at an individual glutamatergic spine causes the depression of nearby GABAergic inhibitory synapses (within 3 μm), whereas more distant ones are potentiated. Notably, L-type calcium channels and calpain are required for this plasticity spreading. Overall, our data support a model whereby input-specific glutamatergic postsynaptic potentiation induces a spatially regulated rearrangement of inhibitory synaptic strength in the surrounding area through short-range heterosynaptic interactions. Such local coordination of excitatory and inhibitory synaptic plasticity is expected to influence dendritic information processing and integration. [Display omitted] •LTP of individual dendritic spines causes iLTD at neighboring GABAergic synapses•Interaction between single-spine LTP and iLTD occurs in the spatial range of ±3 μm•This iLTD depends on the local dendritic calcium increase and calpain activation•iLTD is associated with reduced gephyrin clustering and increased GABAAR mobility How do neighboring dendritic excitatory and inhibitory synapses interact in hippocampal neurons? Here, Ravasenga et al. reveal the spatial rules of heterosynaptic plasticity by demonstrating that LTP at an individual dendritic spine depresses adjacent GABAergic synapses in the range of ±3 μm.