Somatostatin and parvalbumin inhibitory synapses onto hippocampal pyramidal neurons are regulated by distinct mechanisms

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 115; no. 3; pp. 589 - 594
• Main Authors: Horn, Meryl E., Nicoll, Roger A.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 16.01.2018
• Subjects: Biological Sciences; Brain; Calcium; Calcium channels; Calcium channels (L-type); Calcium channels (R-type); Calcium signalling; Channels; Gephyrin; Glutamatergic transmission; Glutamic acid receptors (ionotropic); Hippocampus; Inhibition; Interneurons; N-Methyl-D-aspartic acid receptors; Neurology; Neurons; Parvalbumin; Proteins; Pyramidal cells; Receptors; Somatostatin; Synapses; TNF inhibitors; inhibition; NMDA receptors; parvalbumin; somatostatin; voltage-gated calcium channels
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1719523115

Excitation–inhibition balance is critical for optimal brain function, yet the mechanisms underlying the tuning of inhibition from different populations of inhibitory neurons are unclear. Here, we found evidence for two distinct pathways through which excitatory neurons cell-autonomously modulate inhibitory synapses. Synapses from parvalbumin-expressing interneurons onto hippocampal pyramidal neurons are regulated by neuronal firing, signaling through L-type calcium channels. Synapses from somatostatin-expressing interneurons are regulated by NMDA receptors, signaling through R-type calcium channels. Thus, excitatory neurons can cell-autonomously regulate their inhibition onto different subcellular compartments through their input (glutamatergic signaling) and their output (firing). Separately, while somatostatin and parvalbumin synapses onto excitatory neurons are both dependent on a common set of post-synaptic proteins, including gephyrin, collybistin, and neuroligin-2, decreasing neuroligin-3 expression selectively decreases inhibition from somatostatin interneurons, and overexpression of neuroligin-3 selectively enhances somatostatin inhibition. These results provide evidence that excitatory neurons can selectively regulate two distinct sets of inhibitory synapses.