-
NeuroImage. Clinical 2022Autosomal recessive Achromatopsia (ACHM) is a rare inherited disorder associated with dysfunctional cone photoreceptors resulting in a congenital absence of cone input...
Autosomal recessive Achromatopsia (ACHM) is a rare inherited disorder associated with dysfunctional cone photoreceptors resulting in a congenital absence of cone input to visual cortex. This might lead to distinct changes in cortical architecture with a negative impact on the success of gene augmentation therapies. To investigate the status of the visual cortex in these patients, we performed a multi-centre study focusing on the cortical structure of regions that normally receive predominantly cone input. Using high-resolution T1-weighted MRI scans and surface-based morphometry, we compared cortical thickness, surface area and grey matter volume in foveal, parafoveal and paracentral representations of primary visual cortex in 15 individuals with ACHM and 42 normally sighted, healthy controls (HC). In ACHM, surface area was reduced in all tested representations, while thickening of the cortex was found highly localized to the most central representation. These results were comparable to more widespread changes in brain structure reported in congenitally blind individuals, suggesting similar developmental processes, i.e., irrespective of the underlying cause and extent of vision loss. The cortical differences we report here could limit the success of treatment of ACHM in adulthood. Interventions earlier in life when cortical structure is not different from normal would likely offer better visual outcomes for those with ACHM.
Topics: Adult; Color Vision Defects; Fovea Centralis; Humans; Primary Visual Cortex; Retinal Cone Photoreceptor Cells; Visual Cortex
PubMed: 34959047
DOI: 10.1016/j.nicl.2021.102925 -
The Journal of Physiology Jun 2009Anatomical superposition of the cortical projections from the overlapping visual fields of the two eyes does not make it obvious how the disposition of objects in the... (Review)
Review
Anatomical superposition of the cortical projections from the overlapping visual fields of the two eyes does not make it obvious how the disposition of objects in the third dimension is encoded. Hubel and Wiesel's demonstration that units in the primary visual cortex of the mammal respond preferentially to elongated contours of specific orientation encouraged the inquiry into whether binocular disparity might not similarly be represented as an attribute interdigitated within the orderly progression of position. When this was found to indeed be the case, this entrained a brisk research activity into the disparity of receptive fields of single units in the primary visual cortex and the influence on their response of the three-dimensional locations of outside world stimuli. That cells' preferred orientations covered the whole gamut whereas space perception required only horizontal disparity was an apparent paradox that needed resolution. A connection with an observer's stereoscopic performance was made by the discovery that cells in the primate primary visual cortex display good tuning to the disparity in random-dot stereograms. But a wide gap still remains between the properties of these cortical units and human stereo thresholds in simple target configurations, let alone depth judgments in which perceptual and cognitive factors enter. When the neural circuits in the primary visual cortex that are involved in processing depth are eventually traced in detail they will also need to have properties that allow for the plasticity in learning and experience.
Topics: Animals; Cats; Humans; Primates; Retina; Vision, Binocular; Visual Cortex; Visual Fields; Visual Pathways
PubMed: 19525565
DOI: 10.1113/jphysiol.2009.170175 -
ELife Jan 2022Understanding cortical microcircuits requires thorough measurement of physiological properties of synaptic connections formed within and between diverse subclasses of...
Understanding cortical microcircuits requires thorough measurement of physiological properties of synaptic connections formed within and between diverse subclasses of neurons. Towards this goal, we combined spatially precise optogenetic stimulation with multicellular recording to deeply characterize intralaminar and translaminar monosynaptic connections to supragranular (L2/3) neurons in the mouse visual cortex. The reliability and specificity of multiphoton optogenetic stimulation were measured across multiple Cre lines, and measurements of connectivity were verified by comparison to paired recordings and targeted patching of optically identified presynaptic cells. With a focus on translaminar pathways, excitatory and inhibitory synaptic connections from genetically defined presynaptic populations were characterized by their relative abundance, spatial profiles, strength, and short-term dynamics. Consistent with the canonical cortical microcircuit, layer 4 excitatory neurons and interneurons within L2/3 represented the most common sources of input to L2/3 pyramidal cells. More surprisingly, we also observed strong excitatory connections from layer 5 intratelencephalic neurons and potent translaminar inhibition from multiple interneuron subclasses. The hybrid approach revealed convergence to and divergence from excitatory and inhibitory neurons within and across cortical layers. Divergent excitatory connections often spanned hundreds of microns of horizontal space. In contrast, divergent inhibitory connections were more frequently measured from postsynaptic targets near each other.
Topics: Action Potentials; Animals; Brain; Cell Line; Excitatory Postsynaptic Potentials; Female; Male; Mice; Optogenetics; Photons; Primary Visual Cortex; Pyramidal Cells; Reproducibility of Results; Synapses; Synaptic Transmission; Visual Cortex
PubMed: 35060903
DOI: 10.7554/eLife.71103 -
NeuroImage. Clinical 2021Cerebral visual impairment (CVI) is associated with a wide range of visual perceptual deficits including global motion processing. However, the underlying...
Cerebral visual impairment (CVI) is associated with a wide range of visual perceptual deficits including global motion processing. However, the underlying neurophysiological basis for these impairments remain poorly understood. We investigated global motion processing abilities in individuals with CVI compared to neurotypical controls using a combined behavioral and multi-modal neuroimaging approach. We found that CVI participants had a significantly higher mean motion coherence threshold (determined using a random dot kinematogram pattern simulating optic flow motion) compared to controls. Using functional magnetic resonance imaging (fMRI), we investigated activation response profiles in functionally defined early (i.e. primary visual cortex; area V1) and higher order (i.e. middle temporal cortex; area hMT+) stages of motion processing. In area V1, responses to increasing motion coherence were similar in both groups. However, in the CVI group, activation in area hMT+ was significantly reduced compared to controls, and consistent with a surround facilitation (rather than suppression) response profile. White matter tract reconstruction obtained from high angular resolution diffusion imaging (HARDI) revealed evidence of increased mean, axial, and radial diffusivities within cortico-cortical (i.e. V1-hMT+), but not thalamo-hMT+ connections. Overall, our results suggest that global motion processing deficits in CVI may be associated with impaired signal integration and segregation mechanisms, as well as white matter integrity at the level of area hMT+.
Topics: Humans; Magnetic Resonance Imaging; Motion; Motion Perception; Photic Stimulation; Primary Visual Cortex; Vision Disorders; Visual Cortex; Visual Perception
PubMed: 34628303
DOI: 10.1016/j.nicl.2021.102821 -
Frontiers in Computational Neuroscience 2022A compact analytic model is proposed to describe the combined orientation preference (OP) and ocular dominance (OD) features of simple cells and their mutual constraints...
A compact analytic model is proposed to describe the combined orientation preference (OP) and ocular dominance (OD) features of simple cells and their mutual constraints on the spatial layout of the combined OP-OD map in the primary visual cortex (V1). This model consists of three parts: (i) an anisotropic Laplacian (AL) operator that represents the local neural sensitivity to the orientation of visual inputs; and (ii) obtain a receptive field (RF) operator that models the anisotropic spatial projection from nearby neurons to a given V1 cell over scales of a few tenths of a millimeter and combines with the AL operator to give an overall OP operator; and (iii) a map that describes how the parameters of these operators vary approximately periodically across V1. The parameters of the proposed model maximize the neural response at a given OP with an OP tuning curve fitted to experimental results. It is found that the anisotropy of the AL operator does not significantly affect OP selectivity, which is dominated by the RF anisotropy, consistent with Hubel and Wiesel's original conclusions that orientation tuning width of V1 simple cell is inversely related to the elongation of its RF. A simplified and idealized OP-OD map is then constructed to describe the approximately periodic local OP-OD structure of V1 in a compact form. It is shown explicitly that the OP map can be approximated by retaining its dominant spatial Fourier coefficients, which are shown to suffice to reconstruct its basic spatial structure. Moreover, this representation is a suitable form to analyze observed OP maps compactly and to be used in neural field theory (NFT) for analyzing activity modulated by the OP-OD structure of V1. Application to independently simulated V1 OP structure shows that observed irregularities in the map correspond to a spread of dominant coefficients in a circle in Fourier space. In addition, there is a strong bias toward two perpendicular directions when only a small patch of local map is included. The bias is decreased as the amount of V1 included in the Fourier transform is increased.
PubMed: 35185503
DOI: 10.3389/fncom.2022.659316 -
The Journal of Neuroscience : the... Jan 2019To reduce statistical redundancy of natural inputs and increase the sparseness of coding, neurons in primary visual cortex (V1) show tuning for stimulus size and...
To reduce statistical redundancy of natural inputs and increase the sparseness of coding, neurons in primary visual cortex (V1) show tuning for stimulus size and surround suppression. This integration of spatial information is a fundamental, context-dependent neural operation involving extensive neural circuits that span across all cortical layers of a V1 column, and reflects both feedforward and feedback processing. However, how spatial integration is dynamically coordinated across cortical layers remains poorly understood. We recorded single- and multiunit activity and local field potentials across V1 layers of awake mice (both sexes) while they viewed stimuli of varying size and used dynamic Bayesian model comparisons to identify when laminar activity and interlaminar functional interactions showed surround suppression, the hallmark of spatial integration. We found that surround suppression is strongest in layer 3 (L3) and L4 activity, where suppression is established within ∼10 ms after response onset, and receptive fields dynamically sharpen while suppression strength increases. Importantly, we also found that specific directed functional connections were strongest for intermediate stimulus sizes and suppressed for larger ones, particularly for connections from L3 targeting L5 and L1. Together, the results shed light on the different functional roles of cortical layers in spatial integration and on how L3 dynamically coordinates activity across a cortical column depending on spatial context. Neurons in primary visual cortex (V1) show tuning for stimulus size, where responses to stimuli exceeding the receptive field can be suppressed (surround suppression). We demonstrate that functional connectivity between V1 layers can also have a surround-suppressed profile. A particularly prominent role seems to have layer 3, the functional connections to layers 5 and 1 of which are strongest for stimuli of optimal size and decreased for large stimuli. Our results therefore point toward a key role of layer 3 in coordinating activity across the cortical column according to spatial context.
Topics: Algorithms; Animals; Evoked Potentials; Feedback, Physiological; Female; Male; Mice; Mice, Inbred C57BL; Photic Stimulation; Space Perception; Visual Cortex; Visual Fields; Visual Pathways; Visual Perception
PubMed: 30459226
DOI: 10.1523/JNEUROSCI.1568-18.2018 -
Journal of Neurochemistry May 2009Endogenous fluorescence signals derived from mitochondria reflect activity-dependent changes in brain metabolism and may be exploited in functional brain imaging.... (Review)
Review
Endogenous fluorescence signals derived from mitochondria reflect activity-dependent changes in brain metabolism and may be exploited in functional brain imaging. Endogenous flavoprotein fluorescence imaging in mice is especially important because many genetically manipulated strains of mice are available and the transparent skull of mice allows transcranial fluorescence imaging of cortical activities. In the primary sensory areas of mice, cortical activities and experience-dependent plasticity have been investigated using transcranial fluorescence imaging. Furthermore, differential imaging, based on stimulus specificity of cortical areas, distinguished activities in higher visual areas around the primary visual cortex from those in primary visual cortex. The combination of transcranial fluorescence imaging with the suppression of cortical activities using photobleaching of flavoproteins is expected to aid in elucidating the roles of sensory cortices including higher areas in mice.
Topics: Animals; Cerebral Cortex; Flavoproteins; Mice; Neuronal Plasticity; Photobleaching; Spectrometry, Fluorescence
PubMed: 19393002
DOI: 10.1111/j.1471-4159.2009.05926.x -
Cell Reports Jun 2022A long-range circuit linking the medial frontal cortex to the primary visual cortex (V1) has been proposed to mediate visual selective attention in mice during visually...
A long-range circuit linking the medial frontal cortex to the primary visual cortex (V1) has been proposed to mediate visual selective attention in mice during visually guided behavior. Here, we use in vivo two-photon functional imaging to measure the endogenous activity of axons of A24b/M2 neurons from this region projecting to layer 1 of V1 (A24b/M2-V1) in mice either passively viewing stimuli or performing a go/no-go visually guided task. We observe that while A24b/M2-V1 are recruited under these conditions, this is not linked to enhancement of neural or behavioral measures of sensory coding. Instead, A24b/M2-V1 activity is associated with licking behavior, modulated by reward, and biased toward the sensory cortical hemisphere representing the stimulus currently being discriminated.
Topics: Animals; Axons; Discrimination, Psychological; Mice; Neurons; Visual Cortex; Visual Perception
PubMed: 35675774
DOI: 10.1016/j.celrep.2022.110932 -
Neuron Jan 2022Sensory neurons are modulated by context. For example, in mouse primary visual cortex (V1), neuronal responses to the preferred orientation are modulated by the presence...
Sensory neurons are modulated by context. For example, in mouse primary visual cortex (V1), neuronal responses to the preferred orientation are modulated by the presence of superimposed orientations ("plaids"). The effects of this modulation are diverse; some neurons are suppressed, while others have larger responses to a plaid than its components. We investigated whether this diversity could be explained by a unified circuit mechanism. We report that this masking is maintained during suppression of cortical activity, arguing against cortical mechanisms. Instead, the heterogeneity of plaid responses is explained by an interaction between stimulus geometry and orientation tuning. Highly selective neurons are uniformly suppressed by plaids, whereas the effects in weakly selective neurons depend on the spatial configuration of the stimulus, transitioning systematically between suppression and facilitation. Thus, the diverse responses emerge as a consequence of the spatial structure of feedforward inputs, with no need to invoke cortical interactions.
Topics: Animals; Mice; Neurons; Photic Stimulation; Visual Cortex
PubMed: 34735779
DOI: 10.1016/j.neuron.2021.10.017 -
PLoS Computational Biology Nov 2021Finding out the physical structure of neuronal circuits that governs neuronal responses is an important goal for brain research. With fast advances for large-scale...
Finding out the physical structure of neuronal circuits that governs neuronal responses is an important goal for brain research. With fast advances for large-scale recording techniques, identification of a neuronal circuit with multiple neurons and stages or layers becomes possible and highly demanding. Although methods for mapping the connection structure of circuits have been greatly developed in recent years, they are mostly limited to simple scenarios of a few neurons in a pairwise fashion; and dissecting dynamical circuits, particularly mapping out a complete functional circuit that converges to a single neuron, is still a challenging question. Here, we show that a recent method, termed spike-triggered non-negative matrix factorization (STNMF), can address these issues. By simulating different scenarios of spiking neural networks with various connections between neurons and stages, we demonstrate that STNMF is a persuasive method to dissect functional connections within a circuit. Using spiking activities recorded at neurons of the output layer, STNMF can obtain a complete circuit consisting of all cascade computational components of presynaptic neurons, as well as their spiking activities. For simulated simple and complex cells of the primary visual cortex, STNMF allows us to dissect the pathway of visual computation. Taken together, these results suggest that STNMF could provide a useful approach for investigating neuronal systems leveraging recorded functional neuronal activity.
Topics: Action Potentials; Algorithms; Computational Biology; Models, Neurological; Nerve Net; Neurons; Presynaptic Terminals; Primary Visual Cortex
PubMed: 34843460
DOI: 10.1371/journal.pcbi.1009640