Excitatory control of inhibitory neurons is poorly understood due to the difficulty of studying synaptic connectivity in vivo. We inferred such connectivity through analysis of spike timing and validated this inference using juxtacellular and optogenetic control of presynaptic spikes in behaving mice. We observed that neighboring CA1 neurons had stronger connections and that superficial pyramidal cells projected more to deep interneurons. Connection probability and strength were skewed, with a minority of highly connected hubs. Divergent presynaptic connections led to synchrony between interneurons. Synchrony of convergent presynaptic inputs boosted postsynaptic drive. Presynaptic firing frequency was read out by postsynaptic neurons through short-term depression and facilitation, with individual pyramidal cells and interneurons displaying a diversity of spike transmission filters. Additionally, spike transmission was strongly modulated by prior spike timing of the postsynaptic cell. These results bridge anatomical structure with physiological function. English, McKenzie, et al. identify, validate, and quantify monosynaptic connections between pyramidal cells and interneurons, using the spike timing of pre- and postsynaptic neurons in vivo. Their large-scale method uncovers a backbone of connectivity rules in the hippocampus CA1 circuit.
Bibliographical noteFunding Information:
We thank Dan Levenstein for assistance with the short-term plasticity modeling. We thank Asohan Amarasingham, Antonio Fernandez Ruiz, Gabrielle Girardeau, Azahara Oliva, Peter Petersen, Jonathan Platkiewicz, Katherine Nagel, Lisa Roux, Luke Sjulson, Eran Stark, Rachel Swanson, Viktor Varga, and Brendon Watson for insightful comments and discussion; Robert Averkin and Manuel Valero for advice regarding juxtacellular recording techniques; Leora Fox for editorial assistance with the manuscript; and Oren Wilcox for technical assistance. Euisik Yoon is a founder and shareholder of the NeuroLight Technologies. Funding: G.B.: NIMH MH54671 , NINDS NS 090583 , NS104590-01 ; Simons Foundation ; E.Y.: NINDS NS090526 , NSF PIRE ; NIH R21EB01922 ; S.M.: NIMH F32 MH107159 .
Funding: G.B.: NIMH MH54671, NINDS NS 090583, NS104590-01; Simons Foundation; E.Y.: NINDS NS090526, NSF PIRE; NIH R21EB01922; S.M.: NIMH F32 MH107159.
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