Feedback of the amygdala globally modulates visual response of primary visual cortex in the cat.

The amygdala is an important center for emotional behavior, and it influences other cortical regions. Long feedback projections from the amygdala to the primary visual cortex were recently reported in the cat and monkey, two animal models for vision research. However, the detailed functional roles of these extensive projections still remain largely unknown. In this study, intrinsic signal optical imaging was used to investigate the visually driven responses of the primary visual cortex of cats as focal drugs were injected into the basal nucleus of the amygdala. Both the visually evoked global signals and differential signals in the functional maps of the primary visual cortex were enhanced or reduced by glutamate-induced activation or GABA-induced deactivation of neurons in the amygdala, respectively. This modulation was found to be non-selective, consistent with the gain control mechanism-both the preferred orientation and its mapped orientation tuning width remained unchanged. The single unit recordings showed similar results supporting the above observations. These results suggest that the distal feedback signals of the amygdala enhance the primary sensory information processing in a non-selective, gain-control fashion. This provides direct neurophysiological evidence and insight for previous studies on emotional-cue related psychological studies.

Neuroprotective effect of transcorneal electrical stimulation on ischemic damage in the rat retina.

Some previous studies have showed that transcorneal electrical stimulation (TES) could protect retinal neurons in certain rodent models. However, it is not yet clear whether TES could also definitely protect retinal neurons against ischemic insults. In the present study, we hypothesized that TES had such a neuroprotective effect and further investigated its underlying mechanism. Adult female Sprague-Dawley (SD) rats received TES treatment every other day after ocular ischemia was induced by elevating the intraocular pressure to 120 mm Hg for 60 min. Retinal ganglion cells (RGCs) were labeled retrogradely 7 days before ischemia and were counted 7 and 14 days later. At the same time points, retinal function was assessed by scotopic electroretinography (ERG), combined with retinal histological analysis. The glutamine synthetase (GS) immunoreactivity was compared between ischemic retinas with TES and those with sham stimulation under identical confocal laser microscope conditions. The immunohistochemical indications were confirmed by Western blot analysis. Higher mean density of RGCs was quantified in TES treated retinas compared to retinas with sham stimulation on days 7 and 14 after ischemia. Similarly, histological analysis showed that TES better preserved the mean thickness of separate retinal layers. ERG studies indicated that by undergoing TES treatment, the b-wave amplitude was also significantly preserved on day 7 after ischemia and recovered robustly on day 14. Immunohistochemical and Western blot analysis both revealed that GS levels remarkably increased after TES and lasted for at least 7 days. Our results indicate that TES can protect retinal neurons against ischemic insults, probably related to increasing levels of GS localized in Müller cells. These findings suggest a new approach for potential clinical application to ocular ischemic diseases.

Feedback from area 21a influences orientation but not direction maps in the primary visual cortex of the cat.

In the monkey's visual cortex, there are two well-documented information processing streams: the dorsal motion and ventral form/color pathways. Similarly, two corresponding information streams were also found in the cat's visual cortices, and PMLS and area 21a are the gateways for distinct motion and form information processing. It has been shown that the feedback from PMLS solely modulates motion direction, but not orientation response, while the feedback from area 21a modulates form related features, such as spatial frequency dependency and neuronal oblique effect. Here, we postulate that feedback signals from higher cortical areas in the form or the motion information pathway may solely modulate the corresponding properties in neurons in the lower areas of the visual system. To examine the above hypothesis, the impact of feedback from higher area 21a on both orientation and direction maps was investigated in area 17 of the cat using intrinsic signal optical imaging. The results showed that the feedback from area 21a did not affect the amplitude and preference of direction, but did modulate orientation response in area 17, supporting the above hypothesis.

The functional roles of feedback projections in the visual system.

Neurons in the nervous system make connections with ascending feedforward projections and descending feedback projections, as well as projections from neural structures at the identical hierarchical level. These neurons form extremely complicated neural networks and pathways. Compared with the role of the feedforward projection, much less is known concerning the functional roles of the feedback projection. Visual cortex is a good model for studying functional roles of cortical feedback projections which involve many high functions, such as attention, searching and cognition. The present review mainly focused on the functional roles of feedback projections in the visual system.

Anatomical evidence for the projections from the basal nucleus of the amygdala to the primary visual cortex in the cat.

The amygdaloid complex receives information from all sensory systems, especially from vision. In the primate, the amygdala is reciprocally interconnected with some regions of high-order visual cortices such as TE and TEO and only projects to the primary visual cortex (V1, area 17) without direct projection from V1. However, in the cat little is known about the projection from the amygdala to the primary visual cortex. In this study, anatomical study is carried out in cats to determine whether the amygdala sends feedback projection to area 17. FlouroGold, a fluorescent dye was microinjected into area 17 in cats. In the basal nucleus in the amygdala, the retrograde labeled cells (about 30% of total number of the region of interest observed) are distributed widely in an irregular manner, neither in lamina nor in group. The results provide the first anatomical evidence of the amygdala projection to area 17 in the cat, which is a widely used animal model for vision research.

Weakened feedback abolishes neural oblique effect evoked by pseudo-natural visual stimuli in area 17 of the cat.

The psychological oblique effect, a well-known phenomenon that humans and some mammals are more visually sensitive to cardinal (vertical and horizontal) contours than to oblique ones, has commonly been associated with the overrepresentation of cardinal orientations in the visual cortex. In contrast to the oblique effect, however, Essock et al. [E.A. Essock, J.K. DeFord, B.C. Hansen, M.J. Sinai, Oblique stimuli are seen best (not worst!) broad-band stimuli: a horizontal effect, Vision Res. 43 (2003) 1329-1335] reported a psychological 'horizontal effect', in which visual stimuli dominated by oblique orientations were best perceived by human subjects when tested with unique natural broad-band stimuli. In this study, using optical imaging and the similar visual stimuli, we found an overrepresentation of cardinal orientations, i.e. the neural oblique effect, but not 'horizontal effect', in area 17 of the cat. In addition, the oblique effect was abolished by GABA administration in area 21a due to the preferred orientation shifting (6.0%) and decrease of orientation selectivity strength of neurons (26.9%) in area 17. These results indicate a neuronal basis of the oblique effect when animals watch a more natural scene, whereas no evidence was found for the 'horizontal effect'.

Global evaluation of contributions of GABA A, AMPA and NMDA receptors to orientation maps in cat's visual cortex.

Orientation selectivity is a fundamental property of neurons in the visual cortex for form perception. Cortical cells with similar preferred orientations are organized in a columnar manner to form a two-dimensional orientation map in the primary visual cortex (area 17). There are several mechanisms underlying the generation of orientation selectivity at the single neuron level; however, their relative contributions to the overall orientation maps are unclear. Using optical imaging combined with in vivo application of AMPA, NMDA and GABA A receptor antagonists, we observed that CNQX or AP-5 weakened the orientation map of area 17, whereas simultaneous application of both antagonists abolished the map completely. Furthermore, removal of GABAergic inhibition by application of bicuculline and/or picrotoxin, which are GABA A receptor antagonists, led to cortical epilepsy and wiped out the orientation map completely; although low doses of bicuculline enhanced the orientation map. The orientation map reappeared after the bicuculline-induced epilepsy was prevented by applying CNQX to partially block the excitatory inputs. During those drug application experiments that did not abolish orientation selectivity, the remained map pattern was unchanged. Bicuculline combined with CNQX could only reduce the amplitude of orientation mapping signals but could not alter the preferred orientation maps. These results indicate that the excitatory inputs to cortical neurons are essential and sufficient for generating orientation maps. However, intracortical GABAergic inhibition is necessary to sustain a normal excitation-inhibition balance in area 17. Overall, both excitatory and inhibitory inputs have spatially homogenous impact on orientation maps.

Evidence for corticocortical connections between areas 7 and 17 in cerebral cortex of the cat.

This study provides the first evidence of direct corticocortical connections between areas 7 and 17 of the cat. Wheat germ agglutinin horseradish peroxidase (WGA-HRP) was administrated by micro-electrophoresis and micro-injection, respectively, into area 17 and area 7 in different hemispheres in eight cats. WGA-HRP labeled pyramidal neurons were observed primarily in layer 5 of areas 7 and 17 indicating that there are reciprocal connections between these areas. Optical imaging was used to guide WGA-HRP injections to single orientation columns in area 17. After such restricted injections labeled pyramidal cells were observed in layer 5 of area 7. These pyramidal cells were arranged as discontinuous patches extending across a broad region of area 7. These results suggest that feedback from area 7 to area 17 may arise from specific functional columns in area 7.

Quantitative analysis of brain optical images with 2D C0 complexity measure.

Optical imaging based on intrinsic signals is a powerful method to visualize the activities of neural assembly in the cortex of animals in vivo, especially the detailed functional architecture of the visual cortex. Here, a new index, two-dimensional (2D) C0 complexity has been used to give a quantitative measure of the spatial pattern of the neural activity in orientation maps optically recorded from the visual cortex of cats globally. Results show that 2D C0 complexity could be employed to reveal the dynamic process of generating an orientation map in the visual cortex, and describe the variance of the neural responses in cortical area 17 under high and normal intraocular pressure. This suggests that 2D C0 could be used as a new quantitative measure for analyzing the intrinsic signal optical images.

Slab-like functional architecture of higher order cortical area 21a showing oblique effect of orientation preference in the cat.

Optical imaging based on intrinsic signals is a powerful tool for in vivo studying functional organization of various cortices. Here, the functional architecture of orientation-sensitive neurons in higher order extrastriate cortical area 21a was investigated in cats using optical imaging combined with electrophysiological methods. It is found that neurons in area 21 with similar preferred orientations were functionally organized into a slab-like columnar structure orthogonal to the cortical surface, and the orientation columns were distributed more densely than those in area 17. The responsiveness and activated areas of optical maps visually elicited by the horizontal and vertical gratings were always larger than those by oblique gratings in areas 21a and 17. This neural oblique effect shown in orientation maps was more significant in area 21a than that in area 17. The findings suggest a neuronal mechanism in the higher order extrastriate cortex involving the visual perceptive process of the superiority of cardinal contours.

Visual functional changes during acute elevation of intraocular pressure.

Glaucoma is closely related to elevation of intraocular pressure (IOP). Many studies have done on the effect of chronic elevation of IOP on the retina and optic nerve, but less attention was paid to the effect of acute elevated IOP. Here we briefly review experimental studies on functional changes of the visual system from the retina to the visual cortex under acute elevated IOP condition, which is similar to that of acute primary angle-closure glaucoma.

Differential behavior of simple and complex cells in visual cortex during a brief IOP elevation.

PURPOSE: To study and compare responses of different types of cortical neurons in the primary visual cortex in cats to grating stimuli before and during brief elevation of intraocular pressure (IOP). METHODS: Single-unit electrophysiological recordings were performed in anesthetized and paralyzed cats. The IOP was elevated by injecting saline into the anterior chamber of the cat's eyes through a syringe needle. The IOP was elevated to a level at which the retinal perfusion pressure (arterial pressure minus IOP) was maintained at approximately 30 mmHg for a period of 4 minutes. The responses of simple and complex cells in the primary visual cortex to visually drifting sinusoidal gratings were measured before and during the elevation of IOP. RESULTS: The response amplitude of all the cortical cells in the primary visual cortex declined during a brief elevation of IOP. The decrease in the response of simple cells was always more significant than that of complex cells. The differential decrease between the two major types of cells was independent of the cell's receptive field location and cortical depth. There was a mild tendency for cells with higher preferred spatial frequencies to be more sensitive than those with lower frequencies. The preferred orientation and direction of most cortical cells remained roughly unchanged though their orientation and direction biases decreased. An increase in the animal's blood pressure, which returned the retinal perfusion pressure to a normal level, compensated for the decreased response induced by the elevation of IOP. CONCLUSIONS: The differential effects of a brief elevation of IOP on the response of simple and complex cells in the visual cortex are general and may originate from the retina through the lateral geniculate nucleus (LGN), where different effects of elevation of IOP are exerted on X- and Y-type retinal ganglion cells. The results may suggest differential behavior of neurons tin the parvo and magno pathways of the primate.

Spatial frequency-dependent feedback of visual cortical area 21a modulating functional orientation column maps in areas 17 and 18 of the cat.

The feedback effect of activity of area 21a on orientation maps of areas 17 and 18 was investigated in cats using intrinsic signal optical imaging. A spatial frequency-dependent decrease in response amplitude of orientation maps to grating stimuli was observed in areas 17 and 18 when area 21a was inactivated by local injection of GABA, or by a lesion induced by liquid nitrogen freezing. The decrease in response amplitude of orientation maps of areas 17 and 18 after the area 21a inactivation paralleled the normal response without the inactivation. Application in area 21a of bicuculline, a GABAa receptor antagonist caused an increase in response amplitude of orientation maps of area 17. The results indicate a positive feedback from high-order visual cortical area 21a to lower-order areas underlying a spatial frequency-dependent mechanism.

[Accurate establishment of the retinotopic topography of area 17 in cats by intrinsic signal optical imaging].

The retinotopic topography of area 17 in cats was measured by optical imaging based on intrinsic signals. When stimulated with two neighboring gratings oriented orthogonally each other, which were positioned respectively in the upper and lower visual fields, one piece of cortex that had the retinal projection corresponding to the area around the border of the two stimulus gratings became blurred in the resultant function orientation map, because the neurons in this site received excitatory signals from both the horizontal and the vertical gratings via indirect ways. This functional map of the same cortex was compared with that elicited only by a horizontal or vertical grating stimulation in the whole visual field. Accordingly, the accurate position of the retinotopic eccentricity of the cortex in visual field can be demarcated by calculating the cross correlation coefficient of the two functional maps. Furthermore, compared with the electrophysiological measure of receptive fields of single cortical neurons, the retinotopic eccentricities revealed by optical imaging were identical. This experiment provides a fast and relatively accurate method to calculate the retinotopic eccentricities in a large cortical area of the visual cortex.

Non-dominant eye responses in the dorsal lateral geniculate nucleus of the cat: an intracellular study.

UNLABELLED: While binocularity has been established as an important characteristic of cat visual cortical neurons, neurons in the dorsal lateral geniculate nucleus (LGNd) are commonly believed to be monocular. To test whether binocularity exists at the level of the LGNd, postsynaptic potentials (PSPs) of 101 cells were intracellularly recorded in eight normal and eight monocularly deprived cats while presenting stimuli to either the dominant or non-dominant eyes. The results showed that: (1) About 92% of neurons (45 out of 49) responded to a flashing spot presented to the non-dominant eye. In contrast to the dominant eye responses, the non-dominant eye PSPs usually exhibited the same polarization tendency (hyperpolarization or depolarization) to flashing spot stimuli of light increment or decrement, and most of them were inhibitory (hyperpolarization, 35 out of 45, 78%). (2) The response field (RF) of the non-dominant eye overlapped that of the dominant eye. (3) For most binocular cells, peak-to-peak amplitudes of non-dominant eye PSPs were about half the size (46%) of those of the dominant eye. The peak latencies and half-peak latencies of non-dominant eye PSPs were significantly longer than those of the dominant eye (mean differences were 5.4 ms and 5.6 ms respectively). (4) Most of the binocular cells responded well to contrast reversing gratings presented to the non-dominant eye, and the responses were clearly spatial-frequency tuned. No null phase could be found for non-dominant eye PSPs, no matter the neuron was classified as X or Y type according to dominant eye elicited responses. Some of the cells responded well to drifting gratings presented to the non-dominant eye. (5) We also recorded 52 cells in monocularly deprived cats, and found that 49 cells (94%) showed significant responses to flashing spots presented to the non-dominant eye, a similar percentage to that found in normal cats (92%). CONCLUSION: as strongly monocular neurons, most of LGNd cells could also be driven by the non-dominant eye. The responses evoked by non-dominant eye stimulation differ greatly from those evoked by dominant eye stimulation, and remain intact even without visual experience. These observations suggest an important role of the perigeniculate nucleus in providing binocular inputs to LGNd cells.

Differential dendritic shrinkage of alpha and beta retinal ganglion cells in cats with chronic glaucoma.

PURPOSE: To study changes in the dendritic morphology of retinal ganglion cells (RGCs) in cats with experimental chronic glaucoma. METHODS: Chronic elevation of intraocular pressure (IOP) was produced by injecting endogenous ghost red blood cells into the unilateral anterior chamber of the feline eyes for 1 month. The morphologic features of retrograde-labeled RGCs by bilateral injection of horseradish peroxidase (HRP) into layers A and Aa1 of the lateral geniculate nucleus (LGN) were examined and compared between the normal and glaucomatous eyes. Nissl staining was used for measuring the change in cell density in the retina and the LGN. RESULTS: Quantitative analysis of 720 labeled alpha and beta type RGCs showed that the cell density, body size, maximum dendritic field radius, total dendritic length, and number of branch bifurcations of dendrites decreased significantly in glaucomatous eyes compared with normal ones. The cell loss and shrinkage of dendrites in alpha type ganglion cells in the retina was more pronounced than that in beta type cells. The cell density of all kinds of cells in the retina and LGN monotonically declined with time while IOP was elevated, and cell loss was more significant in large cells than in small ones. CONCLUSION: Progressive cell loss and dendritic damage by chronic elevation of IOP in RGCs and LGN cells are more pronounced in the Y-channel (large cells) than the X-channel (small cells) in feline glaucomatous eyes. The dendritic structure changes and corresponding physiological deficits of RGCs occur before cell death and thus may provide an opportunity for clinical treatment.

Selective loss of orientation column maps in visual cortex during brief elevation of intraocular pressure.

PURPOSE: To compare the orientation column maps elicited by different spatial frequency gratings in cortical area 17 of cats before and during brief elevation of intraocular pressure (IOP). METHODS: IOP was elevated by injecting saline into the anterior chamber of a cat's eye through a syringe needle. The IOP was elevated enough to cause a retinal perfusion pressure (arterial pressure minus IOP) of approximately 30 mm Hg during a brief elevation of IOP. The visual stimulus gratings were varied in spatial frequency, whereas other parameters were kept constant. The orientation column maps of the cortical area 17 were monocularly elicited by drifting gratings of different spatial frequencies and revealed by a brain intrinsic signal optical imaging system. These maps were compared before and during short-term elevation of IOP. RESULTS: The response amplitude of the orientation maps in area 17 decreased during a brief elevation of IOP. This decrease was dependent on the retinal perfusion pressure but not on the absolute IOP. The location of the most visible maps was spatial-frequency dependent. The blurring or loss of the pattern of the orientation maps was most severe when high-spatial-frequency gratings were used and appeared most significantly on the posterior part of the exposed cortex while IOP was elevated. However, the basic patterns of the maps remained unchanged. Changes in cortical signal were not due to changes in the optics of the eye with elevation of IOP. CONCLUSIONS: A stable normal IOP is essential for maintaining normal visual cortical functions. During a brief and high elevation of IOP, the cortical processing of high-spatial-frequency visual information was diminished because of a selectively functional decline of the retinogeniculocortical X pathway by a mechanism of retinal circulation origin.

GABA(A) and GABA(B) receptors mediated inhibition affect the pattern adaptation of relay cells in the dorsal lateral geniculate nucleus (LGNd) of cats.

Pattern adaptation is very important for visual function, while the mechanisms that mediate pattern adaptation, especially in the dorsal lateral geniculate nucleus (LGNd), are still unclear. Iontophoresis of the antagonists and agonists of GABA receptors were employed to separately investigate the contribution of GABA(A) and GABA(B) receptors to pattern adaptation of LGNd cells. When GABA(A) receptors were blocked by bicuculline both the response amplitude of LGNd cells and the degree of adaptation increased significantly. Many neurons showing no pattern adaptation under the normal condition became adapted to a prolonged stimulus. Moreover, the proportion of cells showing adaptation doubled (from 40 to 88%). The mean adaptation index (AI, adapted response amplitude/original response amplitude) was 0.82 during bicuculline application, compared with 0.92 under the control condition. In additional, iontophoresis of baclofen, a selective GABA(B) receptor agonist, decreased the mean response amplitude to grating stimuli to 53% of normal. Nearly half of the neurons increased their adaptation index following baclofen administration and the mean AI increased from 0.89 to 1.01. Iontophoresis of GABA(B) receptor antagonist (CGP35348) could abolish this effect, though it had no significant effect on visual response amplitude and pattern adaptation itself. Iontophoresis of another GABA(B) receptor antagonist, 2-OH-saclofen, also had no significant effect on visual response amplitude and pattern adaptation. These results suggest that both GABA(A) receptors and GABA(B) receptors modulate the pattern adaptation of LGNd cells and are involved in synaptic plasticity.

Anatomical evidence of subcortical contributions to the orientation selectivity and columns of the cat's primary visual cortex.

Physiological studies have demonstrated a subcortical origin for orientation selectivity and the orientation columns of the primary visual cortex. However, there are no anatomical data showing how subcortical cells contribute to this important property. Optical imaging, combined with 1,1'-dioctadecyl-3,3,3,3'-tetramethylin-docarbocyanine perchlolate (DiI) and biocytin retrograde tracing, reveals that relay cells projecting to a single orientation column representing the horizontal meridian were clustered within 300 microm in the dorsal lateral geniculate nucleus (LGN). Interestingly, some labeled cells were located on a line parallel to an iso-elevation line in the LGN. Thus, according to the quantitative projection of the visual field to the LGN (J. Comp. Neurol. 143 (1971) 101), their receptive fields must distribute horizontally in alignment in the visual field providing the first anatomical evidence for Hubel and Wiesel's model of simple cell receptive fields (J. Physiol. 160 (1962) 106).