Chrna2-Martinotti Cells Synchronize Layer 5 Type A Pyramidal Cells via Rebound Excitation

Markus M Hilscher; Richardson N Leão; Steven J Edwards; Katarina E Leão; Klas Kullander

doi:10.1371/journal.pbio.2001392

Chrna2-Martinotti Cells Synchronize Layer 5 Type A Pyramidal Cells via Rebound Excitation

PLoS Biol. 2017 Feb 9;15(2):e2001392. doi: 10.1371/journal.pbio.2001392. eCollection 2017 Feb.

Authors

Markus M Hilscher^{1

2}, Richardson N Leão^{1

2}, Steven J Edwards¹, Katarina E Leão², Klas Kullander¹

Affiliations

¹ Unit of Developmental Genetics, Department of Neuroscience, Uppsala University, Uppsala, Sweden.
² Brain Institute, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.

Abstract

Martinotti cells are the most prominent distal dendrite-targeting interneurons in the cortex, but their role in controlling pyramidal cell (PC) activity is largely unknown. Here, we show that the nicotinic acetylcholine receptor α2 subunit (Chrna2) specifically marks layer 5 (L5) Martinotti cells projecting to layer 1. Furthermore, we confirm that Chrna2-expressing Martinotti cells selectively target L5 thick-tufted type A PCs but not thin-tufted type B PCs. Using optogenetic activation and inhibition, we demonstrate how Chrna2-Martinotti cells robustly reset and synchronize type A PCs via slow rhythmic burst activity and rebound excitation. Moreover, using optical feedback inhibition, in which PC spikes controlled the firing of surrounding Chrna2-Martinotti cells, we found that neighboring PC spike trains became synchronized by Martinotti cell inhibition. Together, our results show that L5 Martinotti cells participate in defined cortical circuits and can synchronize PCs in a frequency-dependent manner. These findings suggest that Martinotti cells are pivotal for coordinated PC activity, which is involved in cortical information processing and cognitive control.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Action Potentials
Animals
Cell Shape
Female
Inhibitory Postsynaptic Potentials / physiology
Interneurons / metabolism*
Male
Mice, Transgenic
Optogenetics
Pyramidal Cells / metabolism*
Receptors, Nicotinic / metabolism*
Time Factors

Substances

CHRNA2 protein, mouse
Receptors, Nicotinic

Grants and funding

Swedish Foundation for International Cooperation in Research and Higher Education (STINT) www.stint.se. Received by RNL and KK. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. American Tinnitus Association www.ata.org. Received by MMH, RNL, and KEL. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Brazilian National Council of Technological and Scientific Development (CNPq) www.cnpq.br. Received by MMH, RNL, and KEL. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Brazilian Federal Agency for Support and Evaluation of Graduate Education (CAPES) www.capes.gov.br. Received by MMH, RNL, and KEL. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Swedish Research Council www.vr.se. Received by KK. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Swedish Brain Foundation www.hjarnfonden.se. Received by KK. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.