title: GABA-A receptor inhibition of local calcium signaling in spines and dendrites.
abstract: Cortical interneurons activate GABA-A receptors to rapidly control electrical and biochemical signaling at pyramidal neurons. Different populations of interneurons are known to uniquely target the soma and dendrites of pyramidal neurons. However, the ability of these interneurons to inhibit Ca(2+) signaling at spines and dendrites is largely unexplored. Here we use whole-cell recordings, two-photon microscopy, GABA uncaging and optogenetics to study dendritic inhibition at layer 5 (L5) pyramidal neurons in slices of mouse PFC. We first show that GABA-A receptors strongly inhibit action potential (AP)-evoked Ca(2+) signals at both spines and dendrites. We find robust inhibition over tens of milliseconds that spreads along the dendritic branch. However, we observe no difference in the amount of inhibition at neighboring spines and dendrites. We then examine the influence of interneurons expressing parvalbumin (PV), somatostatin (SOM), or 5HT3a receptors. We determine that these populations of interneurons make unique contacts onto the apical and basal dendrites of L5 pyramidal neurons. We also show that SOM and 5HT3a but not PV interneurons potently inhibit AP Ca(2+) signals via GABA-A receptors at both spines and dendrites. These findings reveal how multiple interneurons regulate local Ca(2+) signaling in pyramidal neurons, with implications for cortical function and disease.
authors.affiliation: Center for Neural Science, New York University, New York, New York 10003.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Marlin
authors.affiliation: Center for Neural Science, New York University, New York, New York 10003 adam.carter@nyu.edu.
authors.forename: Adam G
authors.initials: AG
authors.lastname: Carter
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D020013:Calcium Signaling / Q000502:physiology*; D003712:Dendrites / Q000502:physiology; D049229:Dendritic Spines / Q000502:physiology*; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009433:Neural Inhibition / Q000502:physiology*; D011963:Receptors, GABA-A / Q000502:physiology*
chemical_list: D011963:Receptors, GABA-A
keywords: calcium signaling; dendrite; inhibition; interneuron; prefrontal cortex; spine