Probing mechanisms of visual spatial attention in mice.

The role of spatial attention for visual perception has been thoroughly studied in primates, but less so in mice. Several behavioral tasks in mice reveal spatial attentional effects, with similarities to observations in primates. Pairing these tasks with large-scale, cell-type-specific techniques could enable deeper access to underlying mechanisms, and help define the utility and limitations of resolving attentional effects on visual perception and neural activity in mice. In this Review, we evaluate behavioral and neural evidence for visual spatial attention in mice; assess how specializations of the mouse visual system and behavioral repertoire impact interpretation of spatial attentional effects; and outline how several measurement and manipulation techniques in mice could precisely test and refine models of attentional modulation across scales.

Spatial modulation of dark versus bright stimulus responses in the mouse visual system.

A fundamental task of the visual system is to respond to both increases and decreases of luminance with action potentials (ON and OFF responses1-4). OFF responses are stronger, faster, and more salient than ON responses in primary visual cortex (V1) of both cats5,6 and primates,7,8 but in ferrets9 and mice,10 ON responses can be stronger, weaker,11 or balanced12 in comparison to OFF responses. These discrepancies could arise from differences in species, experimental techniques, or stimulus properties, particularly retinotopic location in the visual field, as has been speculated;9 however, the role of retinotopy for ON/OFF dominance has not been systematically tested across multiple scales of neural activity within species. Here, we measured OFF versus ON responses across large portions of visual space with silicon probe and whole-cell patch-clamp recordings in mouse V1 and lateral geniculate nucleus (LGN). We found that OFF responses dominated in the central visual field, whereas ON and OFF responses were more balanced in the periphery. These findings were consistent across local field potential (LFP), spikes, and subthreshold membrane potential in V1, and were aligned with spatial biases in ON and OFF responses in LGN. Our findings reveal that retinotopy may provide a common organizing principle for spatial modulation of OFF versus ON processing in mammalian visual systems.

Diminished Cortical Excitation and Elevated Inhibition During Perceptual Impairments in a Mouse Model of Autism.

Sensory impairments are a core feature of autism spectrum disorder (ASD). These impairments affect visual perception and have been hypothesized to arise from imbalances in cortical excitatory and inhibitory activity. There is conflicting evidence for this hypothesis from several recent studies of transgenic mouse models of ASD; crucially, none have measured activity from identified excitatory and inhibitory neurons during simultaneous impairments of sensory perception. Here, we directly recorded putative excitatory and inhibitory population spiking in primary visual cortex (V1) while simultaneously measuring visual perceptual behavior in CNTNAP2-/- knockout (KO) mice. We observed quantitative impairments in the speed, accuracy, and contrast sensitivity of visual perception in KO mice. During these perceptual impairments, stimuli evoked more firing of inhibitory neurons and less firing of excitatory neurons, with reduced neural sensitivity to contrast. In addition, pervasive 3-10 Hz oscillations in superficial cortical layers 2/3 (L2/3) of KO mice degraded predictions of behavioral performance from neural activity. Our findings show that perceptual deficits relevant to ASD may be associated with elevated cortical inhibitory activity along with diminished and aberrant excitatory population activity in L2/3, a major source of feedforward projections to higher cortical regions.

Spatial attention enhances network, cellular and subthreshold responses in mouse visual cortex.

Internal brain states strongly modulate sensory processing during behaviour. Studies of visual processing in primates show that attention to space selectively improves behavioural and neural responses to stimuli at the attended locations. Here we develop a visual spatial task for mice that elicits behavioural improvements consistent with the effects of spatial attention, and simultaneously measure network, cellular, and subthreshold activity in primary visual cortex. During trial-by-trial behavioural improvements, local field potential (LFP) responses to stimuli detected inside the receptive field (RF) strengthen. Moreover, detection inside the RF selectively enhances excitatory and inhibitory neuron responses to task-irrelevant stimuli and suppresses noise correlations and low frequency LFP fluctuations. Whole-cell patch-clamp recordings reveal that detection inside the RF increases synaptic activity that depolarizes membrane potential responses at the behaviorally relevant location. Our study establishes that mice display fundamental signatures of visual spatial attention spanning behavioral, network, cellular, and synaptic levels, providing new insight into rapid cognitive enhancement of sensory signals in visual cortex.

Cortical State Fluctuations across Layers of V1 during Visual Spatial Perception.

Many factors modulate the state of cortical activity, but the importance of cortical state variability for sensory perception remains debated. We trained mice to detect spatially localized visual stimuli and simultaneously measured local field potentials and excitatory and inhibitory neuron populations across layers of primary visual cortex (V1). Cortical states with low spontaneous firing and correlations in excitatory neurons, and suppression of 3- to 7-Hz oscillations in layer 4, accurately predicted single-trial visual detection. Our results show that cortical states exert strong effects at the initial stage of cortical processing in V1 and can play a prominent role for visual spatial behavior in mice.

A novel device for real-time measurement and manipulation of licking behavior in head-fixed mice.

The mouse has become an influential model system for investigating the mammalian nervous system. Technologies in mice enable recording and manipulation of neural circuits during tasks where they respond to sensory stimuli by licking for liquid rewards. Precise monitoring of licking during these tasks provides an accessible metric of sensory-motor processing, particularly when combined with simultaneous neural recordings. There are several challenges in designing and implementing lick detectors during head-fixed neurophysiological experiments in mice. First, mice are small, and licking behaviors are easily perturbed or biased by large sensors. Second, neural recordings during licking are highly sensitive to electrical contact artifacts. Third, submillisecond lick detection latencies are required to generate control signals that manipulate neural activity at appropriate time scales. Here we designed, characterized, and implemented a contactless dual-port device that precisely measures directional licking in head-fixed mice performing visual behavior. We first determined the optimal characteristics of our detector through design iteration and then quantified device performance under ideal conditions. We then tested performance during head-fixed mouse behavior with simultaneous neural recordings in vivo. We finally demonstrate our device's ability to detect directional licks and generate appropriate control signals in real time to rapidly suppress licking behavior via closed-loop inhibition of neural activity. Our dual-port detector is cost effective and easily replicable, and it should enable a wide variety of applications probing the neural circuit basis of sensory perception, motor action, and learning in normal and transgenic mouse models. NEW & NOTEWORTHY Mice readily learn tasks in which they respond to sensory cues by licking for liquid rewards; tasks that involve multiple licking responses allow study of neural circuits underlying decision making and sensory-motor integration. Here we design, characterize, and implement a novel dual-port lick detector that precisely measures directional licking in head-fixed mice performing visual behavior, enabling simultaneous neural recording and closed-loop manipulation of licking.