Visual Cortical Input Research Articles

Monosynaptic Rabies Tracing Reveals Sex- and Age-Dependent Dorsal Subiculum Connectivity Alterations in an Alzheimer's Disease Mouse Model.

The subiculum (SUB), a hippocampal formation structure, is among the earliest brain regions impacted in Alzheimer's disease (AD). Toward a better understanding of AD circuit-based mechanisms, we mapped synaptic circuit inputs to dorsal SUB using monosynaptic rabies tracing in the 5xFAD mouse model by quantitatively comparing the circuit connectivity of SUB excitatory neurons in age-matched controls and 5xFAD mice at different ages for both sexes. Input-mapped brain regions include the hippocampal subregions (CA1, CA2, CA3), medial septum and diagonal band, retrosplenial cortex, SUB, postsubiculum (postSUB), visual cortex, auditory cortex, somatosensory cortex, entorhinal cortex, thalamus, perirhinal cortex (Prh), ectorhinal cortex, and temporal association cortex. We find sex- and age-dependent changes in connectivity strengths and patterns of SUB presynaptic inputs from hippocampal subregions and other brain regions in 5xFAD mice compared with control mice. Significant sex differences for SUB inputs are found in 5xFAD mice for CA1, CA2, CA3, postSUB, Prh, lateral entorhinal cortex, and medial entorhinal cortex: all of these areas are critical for learning and memory. Notably, we find significant changes at different ages for visual cortical inputs to SUB. While the visual function is not ordinarily considered defective in AD, these specific connectivity changes reflect that altered visual circuitry contributes to learning and memory deficits. Our work provides new insights into SUB-directed neural circuit mechanisms during AD progression and supports the idea that neural circuit disruptions are a prominent feature of AD.

Place cells in the claustrum remap under NMDA receptor control.

Place cells are cells that exhibit location‐dependent responses; they have mostly been studied in the hippocampus. Place cells have also been reported in the rat claustrum, an underexplored paracortical region with extensive corto‐cortical connectivity. It has been hypothesised that claustral neuronal responses are anchored to cortical visual inputs. We show rat claustral place cells remap when visual inputs are eliminated from the environment, and that this remapping is NMDA‐receptor‐dependent. Eliminating visual input decreases claustral delta‐band oscillatory activity, increases theta‐band oscillatory activity, and increases simultaneously recorded visual cortical activity. We conclude that, like the hippocampus, claustral place field remapping might be mediated by NMDA receptor activity, and is modulated by visual cortical inputs.

Working memory gates visual input to primate prefrontal neurons.

Visually guided behavior relies on the integration of sensory input and information held in working memory (WM). Yet it remains unclear how this is accomplished at the level of neural circuits. We studied the direct visual cortical inputs to neurons within a visuomotor area of prefrontal cortex in behaving monkeys. We show that the efficacy of visual input to prefrontal cortex is gated by information held in WM. Surprisingly, visual input to prefrontal neurons was found to target those with both visual and motor properties, rather than preferentially targeting other visual neurons. Furthermore, activity evoked from visual cortex was larger in magnitude, more synchronous, and more rapid, when monkeys remembered locations that matched the location of visual input. These results indicate that WM directly influences the circuitry that transforms visual input into visually guided behavior.

Optogenetic auditory fMRI reveals the effects of visual cortical inputs on auditory midbrain response

Sensory cortices contain extensive descending (corticofugal) pathways, yet their impact on brainstem processing – particularly across sensory systems – remains poorly understood. In the auditory system, the inferior colliculus (IC) in the midbrain receives cross-modal inputs from the visual cortex (VC). However, the influences from VC on auditory midbrain processing are unclear. To investigate whether and how visual cortical inputs affect IC auditory responses, the present study combines auditory blood-oxygenation-level-dependent (BOLD) functional MRI (fMRI) with cell-type specific optogenetic manipulation of visual cortex. The results show that predominant optogenetic excitation of the excitatory pyramidal neurons in the infragranular layers of the primary VC enhances the noise-evoked BOLD fMRI responses within the IC. This finding reveals that inputs from VC influence and facilitate basic sound processing in the auditory midbrain. Such combined optogenetic and auditory fMRI approach can shed light on the large-scale modulatory effects of corticofugal pathways and guide detailed electrophysiological studies in the future.

Visual Receptive Field Heterogeneity and Functional Connectivity of Adjacent Neurons in Primate Frontoparietal Association Cortices.

The basic organization principles of the primary visual cortex (V1) are commonly assumed to also hold in the association cortex such that neurons within a cortical column share functional connectivity patterns and represent the same region of the visual field. We mapped the visual receptive fields (RFs) of neurons recorded at the same electrode in the ventral intraparietal area (VIP) and the lateral prefrontal cortex (PFC) of rhesus monkeys. We report that the spatial characteristics of visual RFs between adjacent neurons differed considerably, with increasing heterogeneity from VIP to PFC. In addition to RF incongruences, we found differential functional connectivity between putative inhibitory interneurons and pyramidal cells in PFC and VIP. These findings suggest that local RF topography vanishes with hierarchical distance from visual cortical input and argue for increasingly modified functional microcircuits in noncanonical association cortices that contrast V1.SIGNIFICANCE STATEMENT Our visual field is thought to be represented faithfully by the early visual brain areas; all the information from a certain region of the visual field is conveyed to neurons situated close together within a functionally defined cortical column. We examined this principle in the association areas, PFC, and ventral intraparietal area of rhesus monkeys and found that adjacent neurons represent markedly different areas of the visual field. This is the first demonstration of such noncanonical organization of these brain areas.

Predicting Cortical Dark/Bright Asymmetries from Natural Image Statistics and Early Visual Transforms

The nervous system has evolved in an environment with structure and predictability. One of the ubiquitous principles of sensory systems is the creation of circuits that capitalize on this predictability. Previous work has identified predictable non-uniformities in the distributions of basic visual features in natural images that are relevant to the encoding tasks of the visual system. Here, we report that the well-established statistical distributions of visual features -- such as visual contrast, spatial scale, and depth -- differ between bright and dark image components. Following this analysis, we go on to trace how these differences in natural images translate into different patterns of cortical input that arise from the separate bright (ON) and dark (OFF) pathways originating in the retina. We use models of these early visual pathways to transform natural images into statistical patterns of cortical input. The models include the receptive fields and non-linear response properties of the magnocellular (M) and parvocellular (P) pathways, with their ON and OFF pathway divisions. The results indicate that there are regularities in visual cortical input beyond those that have previously been appreciated from the direct analysis of natural images. In particular, several dark/bright asymmetries provide a potential account for recently discovered asymmetries in how the brain processes visual features, such as violations of classic energy-type models. On the basis of our analysis, we expect that the dark/bright dichotomy in natural images plays a key role in the generation of both cortical and perceptual asymmetries.

Distinct Representation and Distribution of Visual Information by Specific Cell Types in Mouse Superficial Superior Colliculus

The superficial superior colliculus (sSC) occupies a critical node in the mammalian visual system; it is one of two major retinorecipient areas, receives visual cortical input, and innervates visual thalamocortical circuits. Nonetheless, the contribution of sSC neurons to downstream neural activity and visually guided behavior is unknown and frequently neglected. Here we identified the visual stimuli to which specific classes of sSC neurons respond, the downstream regions they target, and transgenic mice enabling class-specific manipulations. One class responds to small, slowly moving stimuli and projects exclusively to lateral posterior thalamus; another, comprising GABAergic neurons, responds to the sudden appearance or rapid movement of large stimuli and projects to multiple areas, including the lateral geniculate nucleus. A third class exhibits direction-selective responses and targets deeper SC layers. Together, our results show how specific sSC neurons represent and distribute diverse information and enable direct tests of their functional role.

Focal projections of cat auditory cortex to the pontine nuclei

The pontine nuclei (PN) receive projections from the auditory cortex (AC) and they are a major source of mossy fibers to the cerebellum. However, they have not been studied in detail using sensitive neuroanatomical tracers, and whether all AC areas contribute to the corticopontine (CP) system is unknown. We characterized the projection patterns of 11 AC areas with WGA-HRP. We also compared them with their corticothalamic and corticocollicular counterparts. A third objective was to analyze the structure of the CP axons and their terminals with BDA. Both tracers confirm that all AC areas projected to lateral, central, and medial ipsilateral pontine divisions. The strongest CP projections were from nontonotopic and polymodal association areas. Preterminal fibers formed single terminal fields having many boutons en passant as well as terminal endings, and there was a specific morphological pattern for each pontine target, irrespective of their areal origin. Thus, axons in the medial division had a simpler terminal architecture (type 1 terminal plexus); both the central and lateral pons received more complex endings (type 2 terminal plexus). Auditory CP topographical distribution resembled visual and somatosensory CP projections, which preserve retinotopy and somatotopy in the pons, respectively. However, the absence of pontine tonotopy suggests that the AC projection topography is unrelated to tonotopy. CP input to the medial and central pons coincides with the somatosensory and visual cortical inputs, respectively, and such overlap might subserve convergence in the cerebellum. In contrast, lateral pontine input may be exclusively auditory.

Positional disparity sensitivity of neurons in the cat accessory optic system

There is considerable evidence supporting the view that the accessory optic system (AOS) and the closely associated nucleus of the optic tract (NOT) provide visual signals used in the control of optokinetic nystagmus (OKN). In frontal-eyed animals such as the cat and primate, the high degree of overlap in the visual fields of each eye, along with a substantial projection from the visual cortex, gives rise to an increased incidence of binocularly responsive neurons in the AOS. In previous studies, my collaborators and I have shown that visual cortical input to the AOS mediates ipsilateral eye responses and high speed tuning, and can function independently of the contralateral eye. However, beyond fairly gross assessments such as these, the binocular interactions of AOS cells have not been subject to detailed examination. The present study set out to determine whether the responses of binocular cells in the dorsal terminal nucleus (DTN) of the AOS are sensitive to horizontal retinal disparity. Single units were recorded from the DTN of anaesthetized, paralysed cats. A large random-dot pattern was moved under computer control at a constant velocity in the preferred and non-preferred direction. Convergent and divergent disparities were generated by deviating the visual axis of the contralateral (dominant) eye using wedge prisms. The responses of DTN units fell into three categories: (1) cells showing tuned excitatory responses (29% or 7 cells) consisting of a marked facilitation for a single or a limited range of disparities; (2) cells broadly tuned for inhibition (25% or 6 cells); and (3) cells relatively insensitive to disparity (46% or 11 cells), showing a relatively flat response profile across the entire range of disparity conditions, or cells without clear tuning. In summary, this study demonstrates that some AOS cells are sensitive to positional disparity and, therefore, this system may provide signals which specify the plane of motion for ocular stabilization. Some of these results have been presented in brief form [Grasse (1991a) Society of Neuroscience Abstracts, 17, 1380].

Pharmacological isolation of visual cortical input to the cat accessory optic system: Effects of intravitreal tetrodotoxin on DTN unit responses

Direction-selective responses were recorded from neurons in the dorsal terminal nucleus (DTN) of the cat accessory optic system before and after intravitreal injections of tetrodotoxin (TTX) into the contralateral eye. After approximately 100 min, direction-selective responses driven through stimulation of the contralateral, injected eye were reduced on average by 90%, while direction-selective responses driven through stimulation of the ipsilateral, uninjected eye were not significantly reduced. By 200 min postinjection, ipsilateral direction-selective responses were either equal to or sometimes greater than control values. In the final stages of these experiments (i.e. between 390-830 min after contralateral eye injections), ipsilateral eye responses were on average 30% higher than control. The effects of retinal blockade of the contralateral eye by TTX show that input from the ipsilateral eye alone is sufficient to mediate direction-selective responses in DTN cells. These results and those observed following bicuculline eye injections reported previously (Grasse et al. 1990) demonstrate that direction-selective responses in the DTN driven through stimulation of the contralateral and ipsilateral eyes arise from independent neural mechanisms located in the retina and visual cortex, respectively. Moreover, these findings also suggest that the contralateral eye exerts an inhibitory influence over ipsilateral eye responses which is diminished by TTX injections into the contralateral eye.

Afferent bases of spatial- and temporal-frequency processing by neurons in the cat's posteromedial lateral suprasylvian cortex: effects of removing areas 17, 18, and 19

1. We investigated whether spatial- and temporal-frequency processing by neurons in the cat's posteromedial lateral suprasylvian (PMLS) extrastriate cortex depends on inputs from ipsilateral areas 17, 18, and 19 (visual cortex; VC) or occurs in parallel with those cortical areas. 2. Single neurons were recorded in PMLS cortex of normal adult cats and adult cats that had ipsilateral VC removed within 24 h before recording. Receptive-field properties were characterized, and responses to sine-wave gratings of different spatial frequencies, contrasts, and temporal frequencies were measured and Fourier analyzed. 3. As in previous studies, removing inputs from VC led to a reduction in the proportion of direction-selective PMLS cells. In addition there were statistically significant reductions in response amplitude and variability, although signal-to-noise ratios were unchanged. Contrast sensitivity also was reduced at all spatial frequencies. Spatial resolution was reduced slightly; however, this reduction appears to be secondary to the overall reduction in response amplitude and sensitivity. 4. The shape of the spatial-frequency contrast-sensitivity functions and the distribution of optimal spatial frequencies were unaffected by removing inputs from VC. In addition, once response threshold was reached, the slope of the contrast-response function (contrast gain) at the optimal spatial frequency was similar for PMLS cells in normal cats and cats with a VC lesion. 5. When tested at the optimal spatial frequency, temporal-frequency bandwidths, high and low temporal-frequency cutoffs, and optimal temporal frequencies were similar for PMLS cells in normal cats and cats with VC removed. 6. The results thus indicate that inputs from VC are important for the elaboration of direction selectivity and affect response amplitude and contrast sensitivity among PMLS neurons. However, visual-cortical inputs have little or no influence on spatial- and temporal-frequency processing by PMLS neurons. These properties depend on inputs from other cortical areas or the thalamus and are processed in parallel with areas 17, 18, and 19.

Organization of visual cortical inputs to the striatum and subsequent outputs to the pallido‐nigral complex in the monkey

To determine the organization of visual inputs and outputs of the striatum, we placed multiple retrograde and anterograde tracers into physiologically identified portions of the striatum known to receive inputs from visual cortex in seven macaques. The injection sites included the tail and genu of the caudate nucleus (14 cases), the head of the caudate (1 case), and the ventral putamen (3 cases). Retrogradely labeled cells were located predominantly in layer 5 of the ipsilateral cortex but were also found in layers 3 and 6. After caudate injections, labeled cells were found both in large, nearly continuous regions of cortex topographically related to the site of the injection, and in several smaller cortical regions that were discontinuous and common to many or all of the injection sites. The continuously labeled regions included nearly all known visual cortical areas, except for the striate cortex. After injections in the rostral tail, the continuously labeled region included the rostral portion of Bonin and Bailey's (Urbana: University of Illinois Press. '47) area TE and adjacent portions of TF, TH, TG, and, occasionally, area 35 (Brodmann, Leipzig: J.A. Barth. '09). After injections into the posterior tail and ventral genu, the labeled region shifted posteriorly in TE and TF, and into TEO and the ventral parts of prestriate areas V4, V3, and (sparsely) V2. As the injection site was advanced into the dorsal genu, the labeled region shifted dorsally toward the parietal lobe, including prestriate areas MT and PO, parietal area PG (Brodmann's area 7), the ventral and lateral intraparietal sulcal areas (VIP and LIP, respectively), and area PE and adjacent area LC (Brodmann's areas 5 and 23, respectively). The discontinuous areas labeled by many different injections included the principal sulcus/frontal eye field region, the anterior cingulate cortex, and the superior temporal polysensory area. Thus, whereas temporal, occipital, and parietal visual cortical areas project into the caudate largely according to proximity, certain multimodal cortical areas seem to have a much wider projection. To determine whether visual cortical areas have additional projections to the caudate beyond the territory of our retrograde injection sites in the tail and genu. 3H-labeled amino acids were injected into areas TE, V4, and MT in three additional monkeys. The topographic location of label in the tail and genu of the caudate in these cases was consistent with the results from injections of retrograde tracers into the caudate.(ABSTRACT TRUNCATED AT 400 WORDS)

The cellular mechanism of thalamic ponto-geniculo-occipital waves

The cellular mechanisms underlying the genesis of thalamic ponto-geniculo-occipital waves were studied in reserpinized cats under urethane anaesthesia. Simultaneous field potential and intracellular recordings were performed in the lateral geniculate nucleus after acute lesions of retinal and visual cortical inputs. In most relay cells, reserpine-induced ponto-geniculo-occipital waves were associated with a transient depolarization that was often interrupted by a unitary inhibitory postsynaptic potential. The depolarization grew in size with membrane hyperpolarization and was accompanied by an increase in membrane conductance. The inhibitory postsynaptic potential is likely to have resulted from the activation of intrageniculate interneurons since perigeniculate cells were always inhibited during the occurrence of ponto-geniculo-occipital waves. Under reserpine, thalamic ponto-geniculo-occipital waves could also be triggered by peribrachial or auditory stimulation. These evoked ponto-geniculo-occipital waves were associated with intracellular events identical to those occurring spontaneously after reserpine administration. In addition, thalamic spindle oscillations were readily blocked by the occurrence of spontaneous or evoked ponto-geniculo-occipital waves. On the basis of the present results and those already published in the literature, the conclusion is reached that lateral geniculate ponto-geniculo-occipital waves result from a nicotinic activation of relay cells and from a parallel muscarinic inhibition of perigeniculate cells by peribrachial afferents. The functional significance of the ponto-geniculo-occipital activity is discussed on the basis of the antagonistic action of these signals on thalamic oscillations. It is proposed that these signals are the central correlates of orienting reactions elicited by sensory stimuli during waking (the so-called eye movement potentials) and by internally generated drives during paradoxical sleep.

The effects of brainstem peribrachial stimulation on neurons of the lateral geniculate nucleus

The intracellular effects of brainstem peribrachial stimulation on lateral geniculate neurons were investigated in the cat. Experiments were performed in cats under barbiturate or urethane anaesthesia and in non-anaesthetized deafferented animals. Most animals were pretreated with reserpine and were acutely deprived of their retinal and visual cortical inputs. Short trains of stimuli triggered a transient depolarization in most relay neurons (latency: 20–30 ms; duration: 200–300 ms). This depolarization could be interrupted by a short-duration unitary inhibitory postsynaptic potential. The depolarization increased with membrane hyperpolarization and was associated with an increase in membrane conductance. The inhibitory postsynaptic potential had an intrathalamic origin and likely resulted from parallel activation of intrageniculate interneurons. The above responses were largely enhanced in reserpinized cats and were completely abolished by small doses of barbiturates. Iontophoretic applications of the nicotinic blocker, hexamethonium, eliminated peribrachial-evoked discharges in these cells, while similar applications of the muscarinic antagonist, scopolamine, were devoid of any effect. The conclusion is reached that the depolarization of lateral geniculate relay neurons by peribrachial afférents represents a direct postsynaptic effect and does not result from a global disinhibitory mechanism involving inhibition of perigeniculate cells and intrageniculate interneurons. This peribrachial-evoked transient excitation of relay neurons results from a nicotinic mechanism.

The effect of visual cortex lesions on vertical optokinetic nystagmus in the cat

Vertical optokinetic nystagmus (VOKN) was measured before and after visual cortex lesions using the magnetic search coil technique. In normal cats, upward motion elicits higher slow phase gain than downward motion, especially at high stimulus velocities. Following decortication, the gain of upward VOKN may be attenuated by as much as 35% at stimulus velocities of 20%/s or more. This high velocity deficit in upward VOKN is consistent with the results of single unit studies of the lateral terminal nucleus (LTN) of the accessory optic system which suggest that visual cortical input (via the LTN) makes a direction specific contribution to the motion sensitivity of VOKN.

Indirect visual cortical input to the deep layers of the hamster's superior colliculus via the basal ganglia.

Anterograde and retrograde tracing techniques were employed to delineate the organization of a visual cortical input to the deep layers of the hamster's superior colliculus which may be mediated by links in the striatum and substantia nigra. Autoradiographic experiments showed that areas 17, 18a, and the cortex medial to area 17 (areas 18b and 29) all projected to the dorsocaudal part of the ipsilateral striatum. This projection was organized so that the rostrocaudal axis of the visual cortex was represented along the antero posterior axis of the striatum. Large posterior neocortical injections which included all of these areas also revealed a weak, crossed corticostriatal pathway. Such injections also demonstrated clear discontinuities in the terminal distribution of the visual corticostriatal projection, similar to those which have been noted after injections of tracers into the motor and premotor cortices. Retrograde tracing experiments showed that the cells of origin of the visual cortical projections to the striatum were medium-sized pyramidal neurons located primarily in the upper portion of lamina V. Anterograde transport of [3H]-leucine and HRP showed that the portion of the striatum heavily innervated by the visual cortex projected to the part of substantial nigra, pars reticulata immediately adjacent to the cerebral peduncle. Injections in the rostral striatum labeled more medial portions of this nucleus. The cells of origin of the striatonigral pathway measured between 13 and 20 micrometers in diameter and they were located primarily in the dorsal and lateral parts of the striatum. Anterograde tracing after substantia nigra, pars reticulata injections revealed a projection to both superior colliculi. The uncrossed pathway terminated primarily as a series of patches throughout the mediolateral and rostrocaudal extents of the lower stratum griseum intermediale and stratum album intermedium. Labeling was also visible in the lateral portion of the stratum griseum profundum. The crossed nigrotectal pathway terminated primarily in the rostrolateral stratum griseum profundum. The cells of origin of the nigrocollicular pathway were fusiform or multipolar cells and were located primarily adjacent to the cerebral peduncle throughout the rostral half of the substantias nigra, par reticulata.

The mode of innervation of the dorsal lateral geniculate nucleus and the pulvinar of the rabbit by axons arising from the visual cortex.

AbstractSections prepared by the Nauta method were used to study the fiber degeneration in the dorsal lateral geniculate nucleus and the pulvinar of the rabbit after lesions in the visual cortex, and sections processed by the Golgi and the Cajal methods provided the material needed to study the normal fiber architecture of these nuclei.Two distinct systems of fibers are recognizable in the dorsal lateral geniculate nucleus and in the pulvinar. One is a transverse system formed by the fiber bundles which run within these nuclei oriented in parallel with the optic tract; some of these bundles mingle with the fibers of the optic tract. The other is a longitudinal system whose fibers course perpendicularly to those of the transverse system. Lesions in the visual cortex produce degeneration within both of these fiber systems, in the geniculate nucleus as well as in the pulvinar. The degenerating transverse fibers are corticopretectal and corticotectal axons, and these send collateral branches into the longitudinal systems of these nuclei.The degenerating longitudinal fibers are of two types. One type consists of fibers which are fine in caliber, give rise to numerous short terminal branches, and degenerate early (undegenerated fibers showing this same morphology are identified in the Golgi preparations). These longitudinal fibers are the collateral branches of the degenerating transverse fibers and at the same time they represent the terminal portions of the fibers which provide the visual cortical input to the geniculate nucleus and the pulvinar. It is noteworthy that within the geniculate nucleus these terminal fibers run along the lines of projection for individual points on the visual field.The second type of degenerating longitudinal fibers is found in the dorsal lateral geniculate nucleus but not in the pulvinar. Its fibers are coarser and degenerate later than the longitudinal fibers described above, and they are probably geniculocortical axons undergoing retrograde degeneration.