Animals are constantly exposed to the time-varying visual world. Because visual perception is modulated by immediately prior visual experience, visual cortical neurons may register recent visual history into a specific form of offline activity and link it to later visual input. To examine how preceding visual inputs interact with upcoming information at the single neuron level, we designed a simple stimulation protocol in which a brief, orientated flashing stimulus was subsequently coupled to visual stimuli with identical or different features. Using in vivo whole-cell patch-clamp recording and functional two-photon calcium imaging from the primary visual cortex (V1) of awake mice, we discovered that a flash of sinusoidal grating per se induces an early, transient activation as well as a long-delayed reactivation in V1 neurons. This late response, which started hundreds of milliseconds after the flash and persisted for approximately 2 s, was also observed in human V1 electroencephalogram. When another drifting grating stimulus arrived during the late response, the V1 neurons exhibited a sublinear, but apparently increased response, especially to the same grating orientation. In behavioral tests of mice and humans, the flashing stimulation enhanced the detection power of the identically orientated visual stimulation only when the second stimulation was presented during the time window of the late response. Therefore, V1 late responses likely provide a neural basis for admixing temporally separated stimuli and extracting identical features in time-varying visual environments.

The primary visual cortex exhibits a late, long response with a latency of Ͼ300 ms and an immediate early response that occurs ϳ100 ms after a visual stimulus. The late response is thought to contribute to visual functions such as sensory perception, iconic memory, working memory, and forming connections between temporally separated stimuli. However, how the visual late response is generated and organized is not completely understood. In the mouse primary visual cortex in vivo, we isolated long-delayed responses by using a brief light-flash stimulus for which the stimulus late response occurred long after the stimulus offset and was not contaminated by the instantaneous response evoked by the stimulus. Using whole-cell patch-clamp recordings, we demonstrated that the late rebound response was shaped by a net-balanced increase in excitatory and inhibitory synaptic conductances, whereas transient imbalances were caused by intermittent inhibitory barrage. In contrast to the common assumption that the neocortical late response reflects a feedback signal from the downstream higher-order cortical areas, our pharmacological and optogenetic analyses demonstrated that the late responses likely have a thalamic origin. Therefore, the late component of a sensory-evoked cortical response should be interpreted with caution.

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Astrocytes in various brain regions exhibit spontaneous intracellular calcium elevations both in vitro and in vivo; however, neither the temporal pattern underlying this activity nor its function has been fully evaluated. Here, we utilized a long-term optical imaging technique to analyze the calcium activity of more than 4000 astrocytes in acute hippocampal slices as well as in the neocortex and hippocampus of head-restrained mice. Although astrocytic calcium activity was largely sparse and irregular, we observed a subset of cells in which the fluctuating calcium oscillations repeated at a regular interval of ∼30 s. These intermittent oscillations i) depended on type 2 inositol 1,4,5-trisphosphate receptors; ii) consisted of a complex reverberatory interaction between the soma and processes of individual astrocytes; iii) did not synchronize with those of other astrocytes; iv) did not require neuronal firing; v) were modulated through cAMP-protein kinase A signaling; vi) were facilitated under pathological conditions, such as energy deprivation and epileptiform hyperexcitation; and vii) were associated with enhanced hypertrophy in astrocytic processes, an early hallmark of reactive gliosis, which is observed in ischemia and epilepsy. Therefore, calcium oscillations appear to be associated with a pathological state in astrocytes.

The primary sensory neocortex generates an internal representation of the environment, and its circuit reorganization is thought to lead to a modification of sensory perception. This reorganization occurs primarily through activity-dependent plasticity and has been well documented in animals during early developmental stages. Here, we describe a new method for the noninvasive induction of long-term plasticity in the mature brain: simple transient visual stimuli (i.e., flashing lights) can be used to induce prolonged modifications in visual cortical processing and visually driven behaviors. Our previous studies have shown that, in the primary visual cortex (V1) of mice, a flashing light stimulus evokes a long-delayed response that persists for seconds. When the mice were repetitively presented with drifting grating stimuli (conditioned stimuli) during the flash stimulus–evoked delayed response period, the V1 neurons exhibited a long-lasting decrease in responsiveness to the conditioned stimuli. The flash stimulus–induced underrepresentation of the grating motion was specific to the direction of the conditioned stimuli and was associated with a decrease in the animal’s ability to detect the motion of the drifting gratings. The neurophysiological and behavioral plasticity both persisted for at least several hours and required N-methyl-d-aspartate receptor activation in the visual cortex. We propose that flashing light stimuli can be used as an experimental tool to investigate the visual function and plasticity of neuronal representations and perception after a critical period of neocortical plasticity.