Joanna Urban-Ciecko1, Erika E Fanselow1, Alison L Barth2. 1. Department of Biological Sciences and Center for the Neural Basis of Cognition, Carnegie Mellon University, 4400 Fifth Avenue, Pittsburgh, PA 15213, USA. 2. Department of Biological Sciences and Center for the Neural Basis of Cognition, Carnegie Mellon University, 4400 Fifth Avenue, Pittsburgh, PA 15213, USA. Electronic address: barth@cmu.edu.
Abstract
BACKGROUND: Understanding the dynamic range for excitatory transmission is a critical component of building a functional circuit diagram for the mammalian brain. Excitatory synaptic transmission is typically studied under optimized conditions, when background activity in the network is low. The range of synaptic function in the presence of inhibitory and excitatory activity within the neocortical circuit is unknown. RESULTS: Paired-cell recordings from pyramidal neurons in acute brain slices of mouse somatosensory cortex show that excitatory synaptic transmission is markedly suppressed during spontaneous network activity: EPSP amplitudes are 2-fold smaller and failure rates are greater than 50%. This suppression is mediated by tonic activation of presynaptic GABAb receptors gated by the spontaneous activity of somatostatin-expressing (Sst) interneurons. Optogenetic suppression of Sst neuron firing was sufficient to enhance EPSP amplitude and reduce failure rates, effects that were fully reversible and occluded by GABAb antagonists. CONCLUSIONS: These data indicate that Sst interneurons can rapidly and reversibly silence excitatory synaptic connections through the regulation of presynaptic release. This is an unanticipated role for Sst interneurons, which have been assigned a role only in fast GABAa-mediated inhibition. Because Sst interneuron activity has been shown to be regulated by sensory and motor input, these results suggest a mechanism by which functional connectivity and synaptic plasticity could be gated in a state-dependent manner.
BACKGROUND: Understanding the dynamic range for excitatory transmission is a critical component of building a functional circuit diagram for the mammalian brain. Excitatory synaptic transmission is typically studied under optimized conditions, when background activity in the network is low. The range of synaptic function in the presence of inhibitory and excitatory activity within the neocortical circuit is unknown. RESULTS: Paired-cell recordings from pyramidal neurons in acute brain slices of mouse somatosensory cortex show that excitatory synaptic transmission is markedly suppressed during spontaneous network activity: EPSP amplitudes are 2-fold smaller and failure rates are greater than 50%. This suppression is mediated by tonic activation of presynaptic GABAb receptors gated by the spontaneous activity of somatostatin-expressing (Sst) interneurons. Optogenetic suppression of Sst neuron firing was sufficient to enhance EPSP amplitude and reduce failure rates, effects that were fully reversible and occluded by GABAb antagonists. CONCLUSIONS: These data indicate that Sst interneurons can rapidly and reversibly silence excitatory synaptic connections through the regulation of presynaptic release. This is an unanticipated role for Sst interneurons, which have been assigned a role only in fast GABAa-mediated inhibition. Because Sst interneuron activity has been shown to be regulated by sensory and motor input, these results suggest a mechanism by which functional connectivity and synaptic plasticity could be gated in a state-dependent manner.
Authors: Christopher J Price; Bruno Cauli; Endre R Kovacs; Akos Kulik; Bertrand Lambolez; Ryuichi Shigemoto; Marco Capogna Journal: J Neurosci Date: 2005-07-20 Impact factor: 6.167
Authors: Réjan Vigot; Samuel Barbieri; Hans Bräuner-Osborne; Rostislav Turecek; Ryuichi Shigemoto; Yan-Ping Zhang; Rafael Luján; Laura H Jacobson; Barbara Biermann; Jean-Marc Fritschy; Claire-Marie Vacher; Matthias Müller; Gilles Sansig; Nicole Guetg; John F Cryan; Klemens Kaupmann; Martin Gassmann; Thomas G Oertner; Bernhard Bettler Journal: Neuron Date: 2006-05-18 Impact factor: 17.173
Authors: Peter Koppensteiner; Richard Von Itter; Riccardo Melani; Christopher Galvin; Francis S Lee; Ipe Ninan Journal: Biol Psychiatry Date: 2019-05-13 Impact factor: 13.382
Authors: Alexander Naka; Julia Veit; Ben Shababo; Rebecca K Chance; Davide Risso; David Stafford; Benjamin Snyder; Andrew Egladyous; Desiree Chu; Savitha Sridharan; Daniel P Mossing; Liam Paninski; John Ngai; Hillel Adesnik Journal: Elife Date: 2019-03-18 Impact factor: 8.140
Authors: Joanna Urban-Ciecko; Jean-Sebastien Jouhanneau; Stephanie E Myal; James F A Poulet; Alison L Barth Journal: Neuron Date: 2018-02-07 Impact factor: 17.173