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Dually innervated dendritic spines develop in the absence of excitatory activity and resist plasticity through tonic inhibitory crosstalk

Mason S Kleinjan, William C. Buchta, Roberto Ogelman, In-Wook Hwang, Masaaki Kuwajima, Dusten D. Hubbard, Dean J. Kareemo, O. Prikhodko et al.

Neuron, 2023

20 citations

Abstract

Dendritic spines can be directly connected to both inhibitory and excitatory presynaptic terminals, resulting in nanometer-scale proximity of opposing synaptic functions. While dually innervated spines (DiSs) are observed throughout the central nervous system, their developmental timeline and functional properties remain uncharacterized. Here we used a combination of serial section electron microscopy, live imaging, and local synapse activity manipulations to investigate DiS development and function in rodent hippocampus. Dual innervation occurred early in development, even on spines where the excitatory input was locally silenced. Synaptic NMDA receptor currents were selectively reduced at DiSs through tonic GABA B receptor signaling. Accordingly, spine enlargement normally associated with long-term potentiation on singly innervated spines (SiSs) was blocked at DiSs. Silencing somatostatin interneurons or pharmacologically blocking We two acute hippocampal slices from two rats aged 60–61 days old that were anesthetized with halothane and decapitated. The slices (400 m m thickness) were collected from the middle third of the hippocampus and recovered in an inter-face chamber in artificial cerebrospinal fluid for electrophysiology recordings to induce long-term potentiation (LTP) at Schaffer collateral synapses in area CA1 as described previously. 40 Hippocampal slices were fixed within 1 min of the last recording in fixative (6% glutaraldehyde and 2% paraformaldehyde in 0.1 M…

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