Experience shapes activity dynamics and stimulus coding of VIP inhibitory and excitatory cells in visual cortex

Abstract

Cortical circuits are flexible and can change with experience and learning. However, the effects of experience on specific cell types including distinct inhibitory types are not well understood. Here we studied how excitatory and VIP inhibitory cells in layer 2/3 of mouse visual cortex were impacted by visual experience in the context of a behavioral task. Mice learned to perform an image change detection task with a set of eight natural scene images. Subsequently, during 2-photon imaging experiments, mice performed the task with these familiar images and three additional sets of novel images. Familiar images evoked less overall activity in both excitatory and VIP populations, and excitatory cells showed higher selectivity for familiar images. The temporal dynamics of VIP cells differed markedly between novel and familiar images: VIP cells were stimulus-driven for novel images but displayed ramping activity during the inter-stimulus interval for familiar images. Moreover, when a familiar stimulus was omitted, VIP cells showed extended ramping activity until the subsequent image flash. This prominent shift in response dynamics suggests that VIP cells may adopt different modes of processing during familiar versus novel conditions. HIGHLIGHTS• Experience with natural images in a change detection task reduces overall activity of cortical excitatory and VIP inhibitory cells • Encoding of natural images is sharpened with experience in excitatory neurons • VIP cells are stimulus-driven by novel images but show pre-stimulus ramping for familiar images • VIP cells show strong ramping activity during the omission of an expected stimulus RESULTS Visual change detection task with familiar and novel imagesWe trained GCaMP6f-expressing transgenic mice to perform a go/no-go visual change detection task with natural scene stimuli ( Figure 1A). In this task, mice are presented with a continuous stream of flashing stimuli (250 ms image flash separated by 500 ms gray screen; Figure 1B). On 'go' trials, a change in image identity occurs at a time unknown to the animal. To earn water rewards, mice must report the image change by licking a reward spout within a 750 ms response window. False alarms are quantified during 'catch' trials in which the repeated image does not change, but licking behavior is measured in a similar time window ( Figure 1B; see Methods). Behavioral training proceeded through a series of stages: mice first learned task rules with simple full-field gratings of two different orientations with no intervening gray period, followed by introduction of a 500ms gray screen period between grating flashes, and lastly, training of natural scene stimuli ( Figure 1C). During the natural image stage, mice were trained with one set of eight images (image set A) for an extended number of sessions (range = 6-46 sessions with image set A, median = 17 sessions; Figure 1F, Supplemental Figure 1A). Mice viewed each of the eight scenes from the familiar image set an average of 10,350 times prior to the 2-photon imaging stage (range: ...

Characterization of Learning, Motivation, and Visual Perception in Five Transgenic Mouse Lines Expressing GCaMP in Distinct Cell Populations

“…In forthcoming physiological experiments, we will measure neural activity in these mice to characterize cellular correlates of change perception, task-engagement, short-term working memory, and temporal expectation. In an initial study of layer 2/3 excitatory and Vip inhibitory cells in visual cortex, we found that excitatory cells provide selective image coding in the task, whereas Vip cells undergo dramatic changes in activity dynamics with learning (Garrett et al, 2020). Large-scale systematic mapping of activity in different cell classes across the brain will provide insights into how these interactions mediate neural processing to guide behavior and learning.…”

“…Some of the mice included in this study were later used in a set of 2-photon calcium imaging experiments (Garrett et al, 2020) and, as such, they all initially received a headpost and cranial window surgery as previously described (De Vries et al, 2020;Groblewski et al, 2020a). Briefly, surgery was performed on healthy mice that ranged in age from 5 to 12 weeks.…”

“…Change detection is a fundamental behavioral capacity of animals and humans (Rensink, 2002;Elmore et al, 2011;Hagmann and Cook, 2013;Pearson and Platt, 2013), and the visual cortex of mice and primates is implicated in the detection of changes in visual features (Womelsdorf et al, 2006;Glickfeld et al, 2013;Brunet et al, 2014). The core task we describe can be used to test perception of various visual features including orientation, contrast, color, and natural images (Glickfeld et al, 2013;Denman et al, 2018;Garrett et al, 2020). Moreover, our task includes features that permit investigation of the physiological correlates of behavior and cognition.…”

“…Moreover, our task includes features that permit investigation of the physiological correlates of behavior and cognition. For instance, this task allows for exploration of stimulus novelty and learning, temporal expectation (Garrett et al, 2020), and short-term memory (Hu et al, 2020).…”

“…To support future studies of neural activity during this task, we have characterized learning and behavior of five Cre driver × GCaMP6 reporter transgenic mouse lines, each of which expresses the GCaMP6 calcium sensor in distinct subpopulations of excitatory or inhibitory cells of the neocortex (Madisen et al, 2015;De Vries et al, 2020;Garrett et al, 2020). These cortical cell subpopulations are believed to play distinct functional roles in cortical computation (Kepecs and Fishell, 2014;Harris and Shepherd, 2015).…”