Behavioral-state modulation of inhibition is context-dependent and cell type specific in mouse visual cortex

“Visual stimuli were generated using the Psychophysics Toolbox package (Brainard, 1997) for MATLAB (Mathworks, MA) and displayed on an LCD monitor (51 29 cm, Dell, UK) placed 20 cm from the right eye, covering 104˚ 72˚ of the visual field.”

“…somatic fluorescence changes and spiking activity in different neuronal types and behavioral contexts In this study, we used the relative changes in fluorescence of the genetically-encoded calcium indicator GCaMP6f as a reporter of the spiking activity of cortical neurons (Chen et al., 2013).”

“In agreement with previous electrophysiological observations (Niell and Stryker, 2010; Keller et al., 2012; Bennett et al., 2013; Polack et al., 2013; Saleem et al., 2013; Erisken et al., 2014; Reimer et al., 2014), we observed that, on average, locomotion increased the amplitude of calcium…”

“(A) Schematic of the connectivity between pyramidal neurons (Pyr) and subtypes of inhibitory neurons, vasoactive intestinal peptide (VIP), somatostatin (SST) and parvalbumin (PV) expressing neurons, established from in vitro studies in V1 (Pfeffer et al., 2013; Jiang et al., 2015).”

“An appealing aspect of the disinhibitory model was the idea of a canonical circuit for gain modulation of sensory responses (Pi et al., 2013).”

“We used two-photon calcium imaging in head-fixed mice that ran freely on a cylindrical treadmill (Figure 1C; Dombeck et al., 2007).”

“We suggest that neuromodulatory inputs triggered by locomotion would not only activate VIP neurons through nicotinic acetylcholine receptors as previously shown (Alitto and Dan, 2012; Arroyo et al., 2014; Fu et al., 2014), but would also directly activate PV, SST, and excitatory neurons.”

“Based on a comprehensive analysis of morphological and electrophysiological properties of inhibitory neurons, a recent in vitro study has identified seven distinct types of cortical interneurons in layer 2/3 (Jiang et al., 2015).”

“The authors distinguished two populations of SST interneurons (see Supplementary Figure 5C of Reimer et al., 2014): Type I cells were inhibited by running while Type II cells were depolarized.”

“In vivo recordings in awake mice have shown that locomotion modulates the response properties of neurons in the primary visual cortex (V1), resulting in an increased gain of excitatory neuron responses to visual stimuli (Niell and Stryker, 2010; Keller et al., 2012; Bennett et al., 2013; Polack et al., 2013; Saleem et…”

“However, a previous study has reported an increase of SST spiking activity in layer 2/3 during locomotion (Polack et al., 2013), an observation that challenges the hypothesis of an SST-cell mediated”

“Finally, in vivo studies have shown that neuromodulatory inputs, cholinergic and noradrenergic, can control the gain and signalto-noise ratio of V1 excitatory neurons during locomotion (Pinto et al., 2013; Polack et al., 2013; Bennett et al., 2014; Lee et al., 2014).”

“Previous work has demonstrated cholinergic facilitation of cortical inhibitory neurons (Kawaguchi, 1997; Xiang et al., 1998; Arroyo et al., 2012; Alitto and Dan, 2012), including SST neurons (Kawaguchi, 1997; Fanselow et al.”

“…agreement with previous electrophysiological observations (Niell and Stryker, 2010; Keller et al., 2012; Bennett et al., 2013; Polack et al., 2013; Saleem et al., 2013; Erisken et al., 2014; Reimer et al., 2014), we observed that, on average, locomotion increased the amplitude of calcium…”

“Indeed, recent studies have shown that projections from the dorsal lateral geniculate nucleus (Erisken et al., 2014; Roth et al., 2016) and from the thalamic latero-posterior nucleus (Roth et al.”

“, 2012; Alitto and Dan, 2012), including SST neurons (Kawaguchi, 1997; Fanselow et al., 2008; Xu et al., 2013; Chen et al., 2015).”

“Considering that neuromodulators can regulate calcium influx (Fucile, 2004; Shen and Yakel, 2009), this second possibility may result from the action of neuromodulators released during locomotion that would increase the amount of calcium entering the neuron in response to each spike.”

“used for demixing spatially overlapping signal sources (Kim and Park, 2007; Langville et al., 2014), as implemented in NIMFA 1.”

“In vivo recordings in awake mice have shown that locomotion modulates the response properties of neurons in the primary visual cortex (V1), resulting in an increased gain of excitatory neuron responses to visual stimuli (Niell and Stryker, 2010; Keller et al., 2012; Bennett et al., 2013; Polack et al., 2013; Saleem et…”

“Similarly, in vitro studies have shown that norepinephrine can depolarize both excitatory (McCormick et al., 1993; Kirkwood et al., 1999) and inhibitory (Kawaguchi and Shindou, 1998) cortical neurons.”

“In addition, these neurons receive subcortical inputs from the dorsal lateral geniculate nucleus as well as neuro- modulatory inputs (Polack et al., 2013; Fu et al., 2014; Lee et al., 2014).”

“Therefore, comparing measures across neurons, rather than across animals, would incorrectly inflate the degrees of freedom with the risk of false positive results for detecting significant differences (Galbraith et al., 2010).”

“Previous work has demonstrated cholinergic facilitation of cortical inhibitory neurons (Kawaguchi, 1997; Xiang et al., 1998; Arroyo et al., 2012; Alitto and Dan, 2012), including SST neurons (Kawaguchi, 1997; Fanselow et al., 2008; Xu et al., 2013; Chen et al., 2015).”

“Using in vivo two-photon calcium imaging in layers 2/3 and 4 in mouse V1, we reveal that locomotion increases the activity of vasoactive intestinal peptide (VIP), somatostatin (SST) and parvalbumin (PV)-positive interneurons during visual stimulation, challenging the disinhibition model.”

“Previous work has demonstrated cholinergic facilitation of cortical inhibitory neurons (Kawaguchi, 1997; Xiang et al., 1998; Arroyo et al., 2012; Alitto and Dan, 2012), including SST neurons (Kawaguchi, 1997; Fanselow et al.”

“In primary sensory areas, neuronal responses to sensory inputs are also modulated by behavioral states, including level of arousal, attention and locomotion (Iriki et al., 1996; Petersen and Crochet, 2013; Bennett et al., 2014; McGinley et al., 2015).”

“Considering that neuromodulators can regulate calcium influx (Fucile, 2004; Shen and Yakel, 2009), this second possibility may result from the action of neuromodulators released during locomotion that would increase the amount of calcium entering the neuron in response to each spike.”

“Similarly, in vitro studies have shown that norepinephrine can depolarize both excitatory (McCormick et al., 1993; Kirkwood et al., 1999) and inhibitory (Kawaguchi and Shindou, 1998) cortical neurons.”

“Image analysis To correct for brain motion after image acquisition, we used 2D plane translation-based image alignment (SIMA 1.2.0, sequential image analysis; Kaifosh et al., 2014).”

“, 2012; Alitto and Dan, 2012), including SST neurons (Kawaguchi, 1997; Fanselow et al., 2008; Xu et al., 2013; Chen et al., 2015).”

“used for demixing spatially overlapping signal sources (Kim and Park, 2007; Langville et al., 2014), as implemented in NIMFA 1.”

“Previous work has demonstrated cholinergic facilitation of cortical inhibitory neurons (Kawaguchi, 1997; Xiang et al., 1998; Arroyo et al., 2012; Alitto and Dan, 2012), including SST neurons (Kawaguchi, 1997; Fanselow et al.”

“Previous work has demonstrated cholinergic facilitation of cortical inhibitory neurons (Kawaguchi, 1997; Xiang et al., 1998; Arroyo et al., 2012; Alitto and Dan, 2012), including SST neurons (Kawaguchi, 1997; Fanselow et al., 2008; Xu et al., 2013; Chen et al., 2015).”

“In primary sensory areas, neuronal responses to sensory inputs are also modulated by behavioral states, including level of arousal, attention and locomotion (Iriki et al., 1996; Petersen and Crochet, 2013; Bennett et al., 2014; McGinley et al., 2015).”

“In order to remove neuropil contamination, we used nonnegative matrix factorization (NMF), which is a low rank matrix decomposition method used for demixing spatially overlapping signal sources (Kim and Park, 2007; Langville et al., 2014), as implemented in NIMFA 1.2.1 (Žitnik and Zupan, 2012).”

“We suggest that neuromodulatory inputs triggered by locomotion would not only activate VIP neurons through nicotinic acetylcholine receptors as previously shown (Alitto and Dan, 2012; Arroyo et al., 2014; Fu et al., 2014), but would also directly activate PV, SST, and excitatory neurons.”

“In primary sensory areas, neuronal responses to sensory inputs are also modulated by behavioral states, including level of arousal, attention and locomotion (Iriki et al., 1996; Petersen and Crochet, 2013; Bennett et al., 2014; McGinley et al., 2015).”

“, 2013), which exert context dependent influence on responses in visual cortex (Pakan et al., 2016).”