Kota S. Sasaki

Targeted Disruption of Cbfa1 Results in a Complete Lack of Bone Formation owing to Maturational Arrest of Osteoblasts

A transcription factor, Cbfa1, which belongs to the runt-domain gene family, is expressed restrictively in fetal development. To elucidate the function of Cbfa1, we generated mice with a mutated Cbfa1 locus. Mice with a homozygous mutation in Cbfa1 died just after birth without breathing. Examination of their skeletal systems showed a complete lack of ossification. Although immature osteoblasts, which expressed alkaline phophatase weakly but not Osteopontin and Osteocalcin, and a few immature osteoclasts appeared at the perichondrial region, neither vascular nor mesenchymal cell invasion was observed in the cartilage. Therefore, our data suggest that both intramembranous and endochondral ossification were completely blocked, owing to the maturational arrest of osteoblasts in the mutant mice, and demonstrate that Cbfa1 plays an essential role in osteogenesis.

The brain mapping of the retrieval of conditioned taste aversion memory using manganese-enhanced magnetic resonance imaging in rats.

Manganese-enhanced MRI (MEMRI) is a newly developed noninvasive imaging technique of brain activities. The signal intensity of MEMRI reflects cumulative activities of the neurons. To validate the use of MEMRI technique to investigate the neural mechanisms of learning and memory, we tried to map brain areas involved in the retrieval of conditioned taste aversion (CTA) memory. CTAs were established to saccharin (conditioned stimulus: CS) by pairing its ingestion with an i.p. injection of LiCl (unconditioned stimulus: US). LiCl solutions (as a robust aversion chemical) of 0.15 M were injected i.p. 15 min after drinking the saccharine solution (CS). After the two times conditionings, these rats showed a robust aversion to the saccharine solution (CS). Rats of the control group were injected saline i.p. instead of LiCl solutions. The MRI signal intensities at the gustatory cortex (GC), the core subregion of the nucleus accumbens (NAcC), the shell subregion of the nucleus accumbens (NAcSh), the ventral pallidum (VP), the central nucleus of amygdala (CeA), the lateral hypothalamus (LH), and the basolateral nucleus of amygdala (BLA) of the conditioned group were higher than those of the control group. There were no significant differences between the conditioned and the control groups in the intensities for other regions, such as the striatum area, motor cortex, cingulate cortex, interstitial nucleus of the posterior limb of the anterior commissure and hippocampus. These indicate that the GC, NAcC, NAcSh, VP, CeA, LH and BLA have important roles in the memory retrieval of CTA.

Complex Cells in the Cat Striate Cortex Have Multiple Disparity Detectors in the Three-Dimensional Binocular Receptive Fields

Along the visual pathway, neurons generally become more specialized for signaling a limited subset of stimulus attributes and become more invariant to changes in the stimulus position within the receptive fields (RFs). One of the likely mechanisms underlying such invariance appears to be pooling of detectors located at different positions. Does such spatial pooling occur for disparity-selective neurons in primary visual cortex? To examine whether the three-dimensional (3D) binocular RFs are constructed by pooling detectors for binocular disparity, we investigated binocular interactions in the 3D space for neurons in the cat striate cortex. Approximately one-third of complex cells showed the spatial pooling of disparity detectors to a significant degree, whereas the majority of simple cells did not. The degree of spatial pooling of disparity detectors along the preferred orientation axis was generally larger than that along the axis orthogonal to the orientation axis. We then reconstructed 3D binocular RFs in their complete form and examined their structures. Disparity tuning curves were compared across positions along the orientation axis in the RFs. A small population of cells appeared to show a gradual shift of the preferred disparity along this axis, indicating that they can potentially signal inclination in the 3D space. However, the majority of cells exhibited a position-invariant disparity tuning. Finally, disparity tuning curves were examined for all oblique angles in addition to horizontal and vertical. Tunings were broadest along the orientation axis as the disparity energy model predicts.

Integration of Multiple Spatial Frequency Channels in Disparity-Sensitive Neurons in the Primary Visual Cortex

For our vivid perception of a 3-D world, the stereoscopic function begins in our brain by detecting slight shifts of image features between the two eyes, called binocular disparity. The primary visual cortex is the first stage of this processing, and neurons there are tuned to a limited range of spatial frequencies (SFs). However, our visual world is generally highly complex, composed of numerous features at a variety of scales, thereby having broadband SF spectra. This means that binocular information signaled by individual neurons is highly incomplete, and combining information across multiple SF bands must be essential for the visual system to function in a robust and reliable manner. In this study, we investigated whether the integration of information from multiple SF channels begins in the cat primary visual cortex. We measured disparity-selective responses in the joint left-right SF domain using sequences of dichoptically flashed grating stimuli consisting of various combinations of SFs and phases. The obtained interaction map in the joint SF domain reflects the degree of integration across different SF channels. Our data are consistent with the idea that disparity information is combined from multiple SF channels in a substantial fraction of complex cells. Furthermore, for the majority of these neurons, the optimal disparity is matched across the SF bands. These results suggest that a highly specific SF integration process for disparity detection starts in the primary visual cortex. SIGNIFICANCE STATEMENT Our visual world is broadband, containing features with a wide range of object scales. On the other hand, single neurons in the primary visual cortex are narrow-band, being tuned narrowly for a specific scale. For robust visual perception, narrow-band information of single neurons must be integrated eventually at some stage. We have examined whether such an integration process begins in the primary visual cortex with respect to binocular processing. The results suggest that a subset of cells appear to combine binocular information across multiple scales. Furthermore, for the majority of these neurons, an optimal parameter of binocular tuning is matched across multiple scales, suggesting the presence of a highly specific neural integration mechanism.

Effects of generalized pooling on binocular disparity selectivity of neurons in the early visual cortex

The key problem of stereoscopic vision is traditionally defined as accurately finding the positional shifts of corresponding object features between left and right images. Here, we demonstrate that the problem must be considered in a four-dimensional parameter space; with respect not only to shifts in space (X, Y), but also spatial frequency (SF) and orientation (OR). The proposed model sums outputs of binocular energy units linearly over the multi-dimensional V1 parameter space (X, Y, SF, OR). Theoretical analyses and physiological experiments show that many binocular neurons achieve sharp binocular tuning properties by pooling the output of multiple neurons with relatively broad tuning. Pooling in the space domain sharpens disparity-selective responses in the SF domain so that the responses to combinations of unmatched left–right SFs are attenuated. Conversely, pooling in the SF domain sharpens disparity selectivity in the space domain, reducing the possibility of false matches. Analogous effects are observed for the OR domain in that the spatial pooling sharpens the binocular tuning in the OR domain. Such neurons become selective to relative OR disparity. Therefore, pooling allows the visual system to refine binocular information into a form more desirable for stereopsis. This article is part of the themed issue ‘Vision in our three-dimensional world’.

Subspace mapping of the three-dimensional spectral receptive field of macaque MT neurons

Neurons in the middle temporal (MT) visual area are thought to represent the velocity (direction and speed) of motion. Previous studies suggest the importance of both excitation and suppression for creating velocity representation in MT; however, details of the organization of excitation and suppression at the MT stage are not understood fully. In this article, we examine how excitatory and suppressive inputs are pooled in individual MT neurons by measuring their receptive fields in a three-dimensional (3-D) spatiotemporal frequency domain. We recorded the activity of single MT neurons from anesthetized macaque monkeys. To achieve both quality and resolution of the receptive field estimations, we applied a subspace reverse correlation technique in which a stimulus sequence of superimposed multiple drifting gratings was cross-correlated with the spiking activity of neurons. Excitatory responses tended to be organized in a manner representing a specific velocity independent of the spatial pattern of the stimuli. Conversely, suppressive responses tended to be distributed broadly over the 3-D frequency domain, supporting a hypothesis of response normalization. Despite the nonspecific distributed profile, the total summed strength of suppression was comparable to that of excitation in many MT neurons. Furthermore, suppressive responses reduced the bandwidth of velocity tuning, indicating that suppression improves the reliability of velocity representation. Our results suggest that both well-organized excitatory inputs and broad suppressive inputs contribute significantly to the invariant and reliable representation of velocity in MT.

Supranormal orientation selectivity of visual neurons in orientation-restricted animals.

Altered sensory experience in early life often leads to remarkable adaptations so that humans and animals can make the best use of the available information in a particular environment. By restricting visual input to a limited range of orientations in young animals, this investigation shows that stimulus selectivity, e.g., the sharpness of tuning of single neurons in the primary visual cortex, is modified to match a particular environment. Specifically, neurons tuned to an experienced orientation in orientation-restricted animals show sharper orientation tuning than neurons in normal animals, whereas the opposite was true for neurons tuned to non-experienced orientations. This sharpened tuning appears to be due to elongated receptive fields. Our results demonstrate that restricted sensory experiences can sculpt the supranormal functions of single neurons tailored for a particular environment. The above findings, in addition to the minimal population response to orientations close to the experienced one, agree with the predictions of a sparse coding hypothesis in which information is represented efficiently by a small number of activated neurons. This suggests that early brain areas adopt an efficient strategy for coding information even when animals are raised in a severely limited visual environment where sensory inputs have an unnatural statistical structure.

Estimating invariant dimensions in V2

Our visual system can robustly detect an important feature in a scene, such as the identity of an object, even when its retinal image can vary substantially. Neural basis for such invariant recognition is thought to be the common property in visual cortex where a cell retains its activity even with large changes in stimuli along a certain dimension. For example, a face-selective cell may keep firing when the viewing angle of the face is changed; a V1 complex cell may remain active when the phase of an oriented grating is changed. A modern approach to identify such invariant dimensions is a semi-automatic analysis of responses to a large number of randomly chosen stimuli; a well-known method is spike-triggered covariance analysis (STC), which has successfully estimated receptive field elements with distinct phases for V1 complex cells [1]. This work aims at generalizing the previous semi-automatic method to reveal invariant dimensions in V2. STC is not suitable for direct applications to V2 cells since these typically have a much higher-degree of nonlinearity compared to V1 cells and since a large number of parameters are needed to characterize V2 cells and therefore STC requires an unrealistic amount of data. Instead, our approach is to assume a population model of V1 cells and analyze their outputs with respect to the responses of a V2 cell, where the latter part uses a Bayesian version of STC [2] for incorporating prior knowledge such as smoothness of receptive field shapes. Previous work on hierarchical analysis of V2 used only a first-order analysis on top of a V1 population model and therefore was not capable of revealing invariant dimensions in V2 [3,4]. We applied our method to a publicly available dataset of 127 V2 cells responding to a large number of natural images [3]. Our analyses revealed that V2 cells often had several invariant dimensions. To characterize these dimensions, we analyzed a quadratic model yielded by Bayesian STC to generate a set of abstract forms of sample stimuli producing optimal or near-optimal responses. The generated set exposed that the invariant dimensions typically represented positional translation, rotational transformation, expansion, compression, or their combination. Quantitative analysis showed a wide variety of invariant dimensions represented in V2, including large transformations like positional translations with the stimulus size, rotations with 45 degrees, and double size changes. Although invariant dimensions of similar kinds are known in higher visual areas, such dimensions have not been reported previously in V2, suggesting that complex invariant representations may already start as early as in V2.

P1-4: Neural Correlates of Fading Illusion Revealed in Responses of V1 Neurons

Visual stimuli without sharp edges fade gradually under visual fixation. This phenomenon is known as Troxler fading or fading illusion. Traditionally, this fading is explained by a hypothesis that physical stimulus is cancelled by a negative image generated in the visual pathway, because the negative image is perceived momentarily when the physical stimulus is removed suddenly. One prediction that may be tested neurophysiologically is that, in the faded or adapted state, visual neurons actually respond to a blank screen, as if they actually ‘see’ the negative image. To examine this prediction in cat V1, we measured the contrast response function of single neurons by presenting flashed grating stimuli of various contrasts (7 contrasts in straddle, ±25%, range and pedestal, within 0–50%, range; negative values for phase reversal) in a rapid succession. Data were analyzed using reverse correlation. The orientation and spatial frequency of gratings were fixed at the optimal value of each cell. We found that V...

Binocular and spatiotemporal analysis of spatial pooling in V1 complex cells

primitives of shape. Physiological studies have suggested that V1 neurons responded strongly at the Medial-Axis (MA) that is located along the equidistance from nearby contours, and that BO-selective neurons were synchronized at stimulus onset. We hypothesized that a number of synchronized signals from BO neurons in V2 begin traveling from contours, and reach the location of MA in V1 at the same time. Thus, neurons at MA receive multiple responses within a short time window, resulting in strong responses at MA. It is expected that the onset synchronization of BO neurons plays a crucial role in the representation of primitive shape by means of MA. To examine plausibility of the hypothesis, we tested a biologically-detailed, recurrent model of V1–V2. The model consisted of firing BO neurons and V1 neurons, both of which were arrayed retinotopically, feedforward and feedback connections between the areas, and lateral connections within V1. We carried out the simulations of the model with a number of stimulus shapes including those from natural images to examine the capability of the model in the primitive representation of shape. The simulation results indicated that V1 neurons showed strong responses at MA with their locations fairly accurate (70% correct). The errors of less than 35% were obtained for the reconstruction of shape from the computed MA. These results indicate that if onset synchronization of BO neurons is provided, the V1–V2 recurrent network without any specific mechanism for shape coding is capable of producing good representation of primitive shape by means of MA. Research fund: KAKENHI 21013006, 22300090.