Modulation-Specific and Laminar-Dependent Effects of Acetylcholine on Visual Responses in the Rat Primary Visual Cortex

Abstract

Acetylcholine (ACh) is secreted from cholinergic neurons in the basal forebrain to regions throughout the cerebral cortex, including the primary visual cortex (V1), and influences neuronal activities across all six layers via a form of diffuse extrasynaptic modulation termed volume transmission. To understand this effect in V1, we performed extracellular multi-point recordings of neuronal responses to drifting sinusoidal grating stimuli from the cortical layers of V1 in anesthetized rats and examined the modulatory effects of topically administered ACh. ACh facilitated or suppressed the visual responses of individual cells with a laminar bias: response suppression prevailed in layers 2/3, whereas response facilitation prevailed in layer 5. ACh effects on the stimulus contrast-response function showed that ACh changes the response gain upward or downward in facilitated or suppressed cells, respectively. Next, ACh effects on the signal-to-noise (S/N) ratio and the grating-phase information were tested. The grating-phase information was calculated as the F1/F0 ratio, which represents the amount of temporal response modulation at the fundamental frequency (F1) of a drifting grating relative to the mean evoked response (F0). In facilitated cells, ACh improved the S/N ratio, while in suppressed cells it enhanced the F1/F0 ratio without any concurrent reduction in the S/N ratio. These effects were predominantly observed in regular-spiking cells, but not in fast-spiking cells. Electrophysiological and histological findings suggest that ACh promotes the signaling of grating-phase information to higher-order areas by a suppressive effect on supragranular layers and enhances feedback signals with a high S/N ratio to subcortical areas by a facilitatory effect on infragranular layers. Thus, ACh distinctly and finely controls visual information processing in a manner that is specific for the modulation and cell type and is also laminar dependent.

Effects of Locomotion Extend throughout the Mouse Early Visual System

“…In our data, the most prevalent and strongest suppressive effects seem to occur not in the lower but in the upper part of infragranular layers, potentially corresponding to L5. Our laminar pattern is consistent with recent evidence of antagonistic behavior between layers 2/3 and layer 5 during multisensory processing [22] and during cholinergic influences [18,23]. The discrepancy in the location of the locomotion-suppressed neurons between our data and those of Andermann et al [6] might be methodological, i.e., depth estimates via two-photon microprism imaging versus CSD analysis based on LFPs.…”

Altered visual function in a larval zebrafish knockout of neurodevelopmental risk genepdzk1

“…Second, contrast-gain control horizontally shifts the entire function without changing the function shape, indicating changes of contrast threshold for eliciting any response (i.e., contrast sensitivity). Finally, response-gain control is characterised by changes in the slope or maximum response without changing the baseline of the function [31,32]. In our data, responses were not saturated even at full contrast, making the slope of the function the best reflection of response gain.…”

Cell-specific modulation of plasticity and cortical state by cholinergic inputs to the visual cortex

“…These studies typically involve recording of the spike responses of a population of single units before, during and after local iontophoretic application of ACh or electrical stimulation of the BF. In sensory cortex, these studies have shown that cholinergic modulation can affect contrast gain (Bhattacharyya et al, 2013; Disney et al, 2007; Soma et al, 2013), orientation and direction selectivity (Herrero et al, 2008; Muller and Singer, 1989; Sato et al, 1987; Sillito and Kemp, 1983; Thiele et al, 2012), spatial integration (Roberts et al, 2005), receptive field size (Bakin and Weinberger, 1996; Kilgard and Merzenich, 1998a) and attention (Herrero et al, 2008). …”

“…Diverse vital brain functions known to be regulated by cholinergic modulation of the neocortex include arousal (Phillis, 1968), attention (Herrero et al, 2008), information processing (Bhattacharyya et al, 2013; Disney et al, 2007; Goard and Dan, 2009; Kosovicheva et al, 2012; Soma et al, 2013), learning and memory (Dotigny et al, 2008; Hasselmo, 2006) and cortical plasticity (Bear and Singer, 1986; Froemke et al, 2007; Kang et al, 2014a; Kang and Vaucher, 2009). The ability of a single cholinergic system to modulate such diverse brain functions, each occurring at specific and distinct timescales, can perhaps be attributed to its specific modulation of varied cell classes that form distinct cortical circuits.…”