Preference-independent saliency map in the mouse superior colliculus.

Detecting salient stimuli in a visual scene is crucial for animal survival, yet how the brain encodes visual saliency remains unclear. Here, using two-photon calcium imaging, we reveal a preference-independent saliency map in the superficial superior colliculus of awake mice. Salient stimuli evoke stronger responses than uniform stimuli in both excitatory and inhibitory neurons, with similar encoding patterns across both cell types.

Characterize neuronal responses to natural movies in the mouse superior colliculus.

While artificial stimuli have been widely used in visual neuroscience and have significantly advanced our understanding of visual processing, they differ dramatically from the natural scenes that animals encounter in the wild. How natural stimuli are encoded in the superior colliculus (SC) and how neuronal responses to artificial and natural stimuli are related remain poorly understood. Here I applied two-photon calcium imaging to record neuronal activity in the mouse superficial SC in response to natural movies.

Calcium Imaging in Mouse Superior Colliculus.

The superior colliculus (SC), an evolutionarily conserved midbrain structure in all vertebrates, is the most sophisticated visual center before the emergence of the cerebral cortex. It receives direct inputs from ~30 types of retinal ganglion cells (RGCs), with each encoding a specific visual feature. It remains elusive whether the SC simply inherits retinal features or if additional and potentially de novo processing occurs in the SC.

Functional cell types in the mouse superior colliculus.

The superior colliculus (SC) represents a major visual processing station in the mammalian brain that receives input from many types of retinal ganglion cells (RGCs). How many parallel channels exist in the SC, and what information does each encode? Here, we recorded from mouse superficial SC neurons under a battery of visual stimuli including those used for classification of RGCs. An unsupervised clustering algorithm identified 24 functional types based on their visual responses.

Balanced Enhancements of Synaptic Excitation and Inhibition Underlie Developmental Maturation of Receptive Fields in the Mouse Visual Cortex.

Neurons in the developing visual cortex undergo progressive functional maturation as indicated by the refinement of their visual feature selectivity. However, changes of the synaptic architecture underlying the maturation of spatial visual receptive fields (RFs) per se remain largely unclear. Here, loose-patch as well as single-unit recordings in layer 4 of mouse primary visual cortex (V1) of both sexes revealed that RF development following an eye-opening period is marked by an increased proportion of cortical neurons with spatially defined RFs, together with the increased signal-to-noise ratio of spiking responses.

Functional Architecture of Motion Direction in the Mouse Superior Colliculus.

Motion vision is important in guiding animal behavior. Both the retina and the visual cortex process object motion in largely unbiased fashion: all directions are represented at all locations in the visual field. We investigate motion processing in the superior colliculus of the awake mouse by optically recording neural responses across both hemispheres.

17-(Allylamino)-17-Demethoxygeldanamycin Enhances Etoposide-Induced Cytotoxicity via the Downregulation of Xeroderma Pigmentosum Complementation Group C Expression in Human Lung Squamous Cell Carcinoma Cells.

Etoposide (VP16) is a topoisomerase II inhibitor and has been used for the treatment of non-small cell lung cancer (NSCLC). Xeroderma pigmentosum complementation group C (XPC) protein is a DNA damage recognition factor in nucleotide excision repair and involved in regulating NSCLC cell proliferation and viability. Heat shock protein 90 (Hsp90) is a ubiquitous molecular chaperone that is responsible for the stabilization and maturation of many oncogenic proteins.

Spatial Asymmetry and Short-Term Suppression Underlie Direction Selectivity of Synaptic Excitation in the Mouse Visual Cortex.

Direction selectivity (DS) of neuronal responses is fundamental for motion detection. With in vivo whole-cell voltage-clamp recordings from layer (L)4 neurons in the mouse visual cortex, we observed a strong correlation between DS and spatial asymmetry in the distribution of excitatory input strengths. This raises an interesting possibility that the latter may contribute to DS.

Cross-Modality Sharpening of Visual Cortical Processing through Layer-1-Mediated Inhibition and Disinhibition.

Cross-modality interaction in sensory perception is advantageous for animals' survival. How cortical sensory processing is cross-modally modulated and what are the underlying neural circuits remain poorly understood. In mouse primary visual cortex (V1), we discovered that orientation selectivity of layer (L)2/3, but not L4, excitatory neurons was sharpened in the presence of sound or optogenetic activation of projections from primary auditory cortex (A1) to V1.

Synaptic Basis for Differential Orientation Selectivity between Complex and Simple Cells in Mouse Visual Cortex.

Unlabelled: In the primary visual cortex (V1), orientation-selective neurons can be categorized into simple and complex cells primarily based on their receptive field (RF) structures. In mouse V1, although previous studies have examined the excitatory/inhibitory interplay underlying orientation selectivity (OS) of simple cells, the synaptic bases for that of complex cells have remained obscure. Here, by combining in vivo loose-patch and whole-cell recordings, we found that complex cells, identified by their overlapping on/off subfields, had significantly weaker OS than simple cells at both spiking and subthreshold membrane potential response levels.

Synaptic mechanisms for generating temporal diversity of auditory representation in the dorsal cochlear nucleus.

In central auditory pathways, neurons exhibit a great diversity of temporal discharge patterns, which may contribute to the parallel processing of auditory signals. How such response diversity emerges in the central auditory circuits remains unclear. Here, we investigated whether synaptic mechanisms can contribute to the generation of the temporal response diversity at the first stage along the central auditory neuraxis.

A feedforward inhibitory circuit mediates lateral refinement of sensory representation in upper layer 2/3 of mouse primary auditory cortex.

Sensory information undergoes ordered and coordinated processing across cortical layers. Whereas cortical layer (L) 4 faithfully acquires thalamic information, the superficial layers appear well staged for more refined processing of L4-relayed signals to generate corticocortical outputs. However, the specific role of superficial layer processing and how it is specified by local synaptic circuits remains not well understood.

Formation of excitation-inhibition balance: inhibition listens and changes its tune.

Recently, Xue, Atallah, and Scanziani reported that excitation/inhibition ratios across cortical pyramidal neurons are equalized by activity-dependent modulations of parvalbumin-neuron mediated feedforward inhibition. Their results raise questions about the developmental formation of this excitation-inhibition balance and the potential activity-dependent synaptic plasticity rules that mediate this process.

Strengthening of Direction Selectivity by Broadly Tuned and Spatiotemporally Slightly Offset Inhibition in Mouse Visual Cortex.

Direction selectivity (DS) of neuronal responses is fundamental for motion detection. How the integration of synaptic excitation and inhibition contributes to DS however remains not well-understood. Here, in vivo whole-cell voltage-clamp recordings in mouse primary visual cortex (V1) revealed that layer 4 simple cells received direction-tuned excitatory inputs but barely tuned inhibitory inputs under drifting-bar stimulation.

Monocular Deprivation in Mice.

Monocular deprivation is an experimental technique to study the ocular dominance plasticity during critical period (Hubel and Wiesel, 1963). Generally one eye of an animal is sutured during critical period, and the sutured eye is re-opened after either less than three days (short term) or more than three days (long term). Here we describe a detailed protocol for short-term and long-term monocular deprivation in mouse (Ma , 2013).

Intracortical multiplication of thalamocortical signals in mouse auditory cortex.

Cortical processing of sensory information begins with the transformation of thalamically relayed signals. We optogenetically silenced intracortical circuits to isolate thalamic inputs to layer 4 neurons and found that intracortical excitation linearly amplified thalamocortical responses underlying frequency and direction selectivity, with spectral range and tuning preserved, and prolonged the response duration. This signal pre-amplification and prolongation enhanced the salience of thalamocortically relayed information and ensured its robust, faithful and more persistent representation.

Linear transformation of thalamocortical input by intracortical excitation.

Neurons in thalamorecipient layers of sensory cortices integrate thalamocortical and intracortical inputs. Although we know that their functional properties can arise from the convergence of thalamic inputs, intracortical circuits could also be involved in thalamocortical transformations of sensory information. We silenced intracortical excitatory circuits with optogenetic activation of parvalbumin-positive inhibitory neurons in mouse primary visual cortex and compared visually evoked thalamocortical input with total excitation in the same layer 4 pyramidal neurons.

Downregulation of cortical inhibition mediates ocular dominance plasticity during the critical period.

Monocular deprivation (MD) during the critical period (CP) shifts ocular dominance (OD) of cortical responsiveness toward the nondeprived eye. The synaptic mechanisms underlying MD-induced OD plasticity, in particular the contribution of cortical inhibition to the plasticity, have remained unsolved. In this study, using in vivo whole-cell voltage-clamp recordings, we revealed eye-specific excitatory and inhibitory synaptic inputs to layer 4 excitatory neurons in mouse primary visual cortex (V1) at a developmental stage close to the end of CP.

Broadening of inhibitory tuning underlies contrast-dependent sharpening of orientation selectivity in mouse visual cortex.

Orientation selectivity (OS) in the visual cortex has been found to be invariant to increases in stimulus contrast, a finding that cannot be accounted for by the original, purely excitatory Hubel and Wiesel model. This property of OS may be important for preserving the quality of perceived stimulus across a range of stimulus intensity. The synaptic mechanisms that can prevent a broadening of OS caused by contrast-dependent strengthening of excitatory inputs to cortical neurons remain unknown.

Broadening of cortical inhibition mediates developmental sharpening of orientation selectivity.

Orientation selectivity (OS) of visual cortical neurons is progressively sharpened during development. However, synaptic circuit mechanisms underlying the OS sharpening remain unclear. In the current study, in vivo whole-cell voltage-clamp recordings from layer 4 excitatory neurons in the developing mouse primary visual cortex revealed changes of orientation tuning profiles of their excitatory and inhibitory inputs during a post-eye-opening period when OS of their spiking responses becomes sharpened.

Broad inhibition sharpens orientation selectivity by expanding input dynamic range in mouse simple cells.

Orientation selectivity (OS) is an emergent property in the primary visual cortex (V1). How OS arises from synaptic circuits remains unsolved. Here, in vivo whole-cell recordings in the mouse V1 revealed that simple cells received broadly tuned excitation and even more broadly tuned inhibition.

Visual representations by cortical somatostatin inhibitory neurons--selective but with weak and delayed responses.

Somatostatin-expressing inhibitory (SOM) neurons in the sensory cortex consist mostly of Martinotti cells, which project ascending axons to layer 1. Due to their sparse distribution, the representational properties of these neurons remain largely unknown. By two-photon imaging guided cell-attached recordings, we characterized visual response and receptive field (RF) properties of SOM neurons and parvalbumin-expressing inhibitory (PV) neurons genetically labeled in the mouse primary visual cortex.

Intervening inhibition underlies simple-cell receptive field structure in visual cortex.

Synaptic inputs underlying spike receptive fields are important for understanding mechanisms of neuronal processing. Using whole-cell voltage-clamp recordings from neurons in mouse primary visual cortex, we examined the spatial patterns of their excitatory and inhibitory synaptic inputs evoked by On and Off stimuli. Neurons with either segregated or overlapped On/Off spike subfields had substantial overlaps between all the four synaptic subfields.

Visual receptive field structure of cortical inhibitory neurons revealed by two-photon imaging guided recording.

Synaptic inhibition plays an important role in shaping receptive field (RF) properties in the visual cortex. However, the underlying mechanisms remain not well understood, partly because of difficulties in systematically studying functional properties of cortical inhibitory neurons in vivo. Here, we established two-photon imaging guided cell-attached recordings from genetically labeled inhibitory neurons and nearby "shadowed" excitatory neurons in the primary visual cortex of adult mice.