Compartmentalization of GABAergic Inhibition by Dendritic Spines

By Chiayu Q. Chiu, G. Lur, Thomas M. Morse, Nicholas T. Carnevale, G. Ellis‐Davies, M. Higley. 2013

299 citations recorded by the source corpus.

Dendritic Precision Strikes The effects of excitatory synaptic inputs are considered to be highly compartmentalized because of the biophysical properties of dendritic spines. Individual inhibitory synapses, however, are thought to affect dendritic integration in a more extended spatial region. Combining optogenetic stimulation of dendrite-targeting γ-aminobutyric acid—mediated interneurons with two-photon calcium imaging in postsynaptic pyramidal cell dendrites, Chiu et al. (p. 759) challenge this latter view. The findings suggest that the effect of an inhibitory synapse can be as compartmentalized as that of an excitatory synapse, provided that the synapses are localized on spine heads. Inhibitory synapses can control individual dendritic spines independently from their neighbors. γ-aminobutyric acid–mediated (GABAergic) inhibition plays a critical role in shaping neuronal activity in the neocortex. Numerous experimental investigations have examined perisomatic inhibitory synapses, which control action potential output from pyramidal neurons. However, most inhibitory synapses in the neocortex are formed onto pyramidal cell dendrites, where theoretical studies suggest they may focally regulate cellular activity. The precision of GABAergic control over dendritic electrical and biochemical signaling is unknown. By using cell type-specific optical stimulation in combination with two-photon calcium (Ca2+) imaging, we show that somatostatin-expressing interneurons exert compartmentalized control over postsynaptic Ca2+ signals within individual dendritic spines. This highly focal inhibitory action is mediated by a subset of GABAergic synapses that directly target spine heads. GABAergic inhibition thus participates in localized control of dendritic electrical and biochemical signaling.

Subfields: Cellular and Molecular Neuroscience, Cognitive Neuroscience

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cellular and Molecular Neuroscience

1. G. Sanacora
2. R. Duman
3. John H. Krystal
4. Nicolas Y. Masse
5. Gregory D. Grant
6. David J. Freedman
7. E. Nestler
8. Bruce S. McEwen

In Cognitive Neuroscience

1. Nicolas Y. Masse
2. Gregory D. Grant
3. David J. Freedman
4. G. Sanacora
5. R. Duman
6. John H. Krystal
7. Gido M. van de Ven
8. Andreas S. Tolias

Citations in the corpus

• Alleviating catastrophic forgetting using context-dependent gating and synaptic stabilization (2018, background): “SOM neurons preferentially target specific dendritic branches of excitatory neurons, suppressing their activity (Chiu et al., 2013).”
• Inhibitory Plasticity Dictates the Sign of Plasticity at Excitatory Synapses (2014, background): “…is no direct report that these synapses are adjacent, recent studies in the hippocampus, in V1, and in other neocortical areas showed that GABAergic inputs can colocalize with glutamatergic synapses at spines (Chen et al., 2012; Chiu et al., 2013), likely favoring crosstalk of signaling mechanisms.”
• Altered connectivity in depression: GABA and glutamate neurotransmitter deficits and reversal by novel treatments (2019, background): “SST interneurons are recruited via NMDA receptor activation, and loss of SST function or blockade of SST-NMDARs reduces input selectivity, thereby causing abberant hyperconnectivity of principal neurons (Chiu et al., 2013); this is consistent with the increase in cortical functional connectivity pro”