Circuitry Underlying Experience-Dependent Plasticity in the Mouse Visual System.

Since the discovery of ocular dominance plasticity, neuroscientists have understood that changes in visual experience during a discrete developmental time, the critical period, trigger robust changes in the visual cortex. State-of-the-art tools used to probe connectivity with cell-type-specific resolution have expanded the understanding of circuit changes underlying experience-dependent plasticity. Here, we review the visual circuitry of the mouse, describing projections from retina to thalamus, between thalamus and cortex, and within cortex. We discuss how visual circuit development leads to precise connectivity and identify synaptic loci, which can be altered by activity or experience. Plasticity extends to visual features beyond ocular dominance, involving subcortical and cortical regions, and connections between cortical inhibitory interneurons. Experience-dependent plasticity contributes to the alignment of networks spanning retina to thalamus to cortex. Disruption of this plasticity may underlie aberrant sensory processing in some neurodevelopmental disorders.

Thalamic inhibition regulates critical-period plasticity in visual cortex and thalamus.

During critical periods of development, experience shapes cortical circuits, resulting in the acquisition of functions used throughout life. The classic example of critical-period plasticity is ocular dominance (OD) plasticity, which optimizes binocular vision but can reduce the responsiveness of the primary visual cortex (V1) to an eye providing low-grade visual input. The onset of the critical period of OD plasticity involves the maturation of inhibitory synapses within V1, specifically those containing the GABAA receptor α1 subunit. Here we show that thalamic relay neurons in mouse dorsolateral geniculate nucleus (dLGN) also undergo OD plasticity. This process depends on thalamic α1-containing synapses and is required for consolidation of the OD shift in V1 during long-term deprivation. Our findings demonstrate that thalamic inhibitory circuits play a central role in the regulation of the critical period. This has far-reaching consequences for the interpretation of studies investigating the molecular and cellular mechanisms regulating critical periods of brain development.

Lateral geniculate neurons projecting to primary visual cortex show ocular dominance plasticity in adult mice.

Experience-dependent plasticity in the mature visual system is widely considered to be cortical. Using chronic two-photon Ca2+ imaging of thalamic afferents in layer 1 of binocular visual cortex, we provide evidence against this tenet: the respective dorsal lateral geniculate nucleus (dLGN) cells showed pronounced ocular dominance (OD) shifts after monocular deprivation in adult mice. Most (86%), but not all, of dLGN cell boutons were monocular during normal visual experience. Following deprivation, initially deprived-eye-dominated boutons reduced or lost their visual responsiveness to that eye and frequently became responsive to the non-deprived eye. This cannot be explained by eye-specific cortical changes propagating to dLGN via cortico-thalamic feedback because the shift in dLGN responses was largely resistant to cortical inactivation using the GABAA receptor agonist muscimol. Our data suggest that OD shifts observed in the binocular visual cortex of adult mice may at least partially reflect plasticity of eye-specific inputs onto dLGN neurons.

Individual differences shape the content of visual representations.

Visually perceiving a stimulus activates a pictorial representation of that item in the brain, but how pictorial is the representation of a stimulus in the absence of visual stimulation? Here I address this question with a review of the literatures on visual imagery (VI), visual working memory (VWM), and visual preparatory templates, all of which require activating visual information in the absence of sensory stimulation. These processes have historically been studied separately, but I propose that they can provide complimentary evidence for the pictorial nature of their contents. One major challenge in studying the contents of visual representations is the discrepant findings concerning the extent of overlap (both cortical and behavioral) between externally and internally sourced visual representations. I argue that these discrepancies may in large part be due to individual differences in VI vividness and precision, the specific representative abilities required to perform a task, appropriateness of visual preparatory strategies, visual cortex anatomy, and level of expertise with a particular object category. Individual differences in visual representative abilities greatly impact task performance and may influence the likelihood of experiences such as intrusive VI and hallucinations, but research still predominantly focuses on uniformities in visual experience across individuals. In this paper I review the evidence for the pictorial content of visual representations activated for VI, VWM, and preparatory templates, and highlight the importance of accounting for various individual differences in conducting research on this topic.

Principles underlying sensory map topography in primary visual cortex.

The primary visual cortex contains a detailed map of the visual scene, which is represented according to multiple stimulus dimensions including spatial location, ocular dominance and stimulus orientation. The maps for spatial location and ocular dominance arise from the spatial arrangement of thalamic afferent axons in the cortex. However, the origins of the other maps remain unclear. Here we show that the cortical maps for orientation, direction and retinal disparity in the cat (Felis catus) are all strongly related to the organization of the map for spatial location of light (ON) and dark (OFF) stimuli, an organization that we show is OFF-dominated, OFF-centric and runs orthogonal to ocular dominance columns. Because this ON-OFF organization originates from the clustering of ON and OFF thalamic afferents in the visual cortex, we conclude that all main features of visual cortical topography, including orientation, direction and retinal disparity, follow a common organizing principle that arranges thalamic axons with similar retinotopy and ON-OFF polarity in neighbouring cortical regions.

The nature of hemispheric specialization for prosody perception.

Recent evidence suggests a relative right-hemispheric specialization for emotional prosody perception, whereas linguistic prosody perception is under bilateral control. It is still unknown, however, how the hemispheric specialization for prosody perception might arise. Two main hypotheses have been put forward. Cue-dependent hypotheses, on the one hand, propose that hemispheric specialization is driven by specialization for the non-prosody-specific processing of acoustic cues. The functional lateralization hypothesis, on the other hand, proposes that hemispheric specialization is dependent on the communicative function of prosody, with emotional and linguistic prosody processing being lateralized to the right and left hemispheres, respectively. In the present study, the functional lateralization hypothesis of prosody perception was systematically tested by instructing one group of participants to evaluate the emotional prosody, and another group the linguistic prosody dimension of bidimensional prosodic stimuli in a dichotic-listening paradigm, while event-related potentials were recorded. The results showed that the right-ear advantage was associated with decreased latencies for an early negativity in the contralateral hemisphere. No evidence was found for functional lateralization. These findings suggest that functional lateralization effects for prosody perception are small and support the structural model of dichotic listening.

Pain and cooperation in patients having dominant-side or nondominant-side phacoemulsification.

PURPOSE: To evaluate the relationship between laterality and perceived pain and cooperation during phacoemulsification under combined topical and intracameral anesthesia. SETTING: University ophthalmology clinic and eye hospital, Kahramanmaras, Turkey. DESIGN: Cohort study. METHODS: Seventy-eight patients with senile cataracts who had ocular surgery were included prospectively. The dominant side was determined with the Edinburg Handedness Inventory. Phacoemulsification and intraocular lens implantation were performed. The surgeon graded the patient's cooperation from 0 (best) to 3 (worst). The duration of surgery was recorded. Another researcher rated perceived pain from 0 (no pain) to 10 (unbearable pain) using a visual analogue scale (VAS). Pain scores and the degree of cooperation for dominant-side and nondominant-side surgery were the primary outcomes. RESULTS: Forty-six patients had surgery in the dominant eye and 32 in the nondominant eye. The 2 groups were similar in age, sex, and severity and type of cataract. The mean VAS score was significantly higher in patients having dominant-side surgery than in those having nondominant-side surgery (P<.01). Similarly, the mean cooperation score was significantly poorer in the patients having dominant-side surgery (P<.05). Visual analogue scores were correlated with patient cooperation (r = 0.890, P<.0001). CONCLUSION: Pain scores were higher in dominant-side surgery for cataract under topical and intracameral anesthesia, which should be kept in mind when selecting anesthesia and in studies in which pain is scored. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Explaining the Colavita visual dominance effect.

The last couple of years have seen a resurgence of interest in the Colavita visual dominance effect. In the basic experimental paradigm, a random series of auditory, visual, and audiovisual stimuli are presented to participants who are instructed to make one response whenever they see a visual target and another response whenever they hear an auditory target. Many studies have now shown that participants sometimes fail to respond to auditory targets when they are presented at the same time as visual targets (i.e., on the bimodal trials), despite the fact that they have no problems in responding to the auditory and visual stimuli when they are presented individually. The existence of the Colavita visual dominance effect provides an intriguing contrast with the results of the many other recent studies showing the superiority of multisensory (over unisensory) information processing in humans. Various accounts have been put forward over the years in order to try and explain the effect, including the suggestion that it reflects nothing more than an underlying bias to attend to the visual modality. Here, the empirical literature on the Colavita visual dominance effect is reviewed and some of the key factors modulating the effect highlighted. The available research has now provided evidence against all previous accounts of the Colavita effect. A novel explanation of the Colavita effect is therefore put forward here, one that is based on the latest findings highlighting the asymmetrical effect that auditory and visual stimuli exert on people's responses to stimuli presented in the other modality.

LASIK for hyperopic astigmatism and presbyopia using micro-monovision with the Carl Zeiss Meditec MEL80 platform.

PURPOSE: To evaluate the monocular and binocular outcomes of LASIK for a micro-monovision protocol for the correction of hyperopic astigmatism and presbyopia. METHODS: A prospective non-comparative case series included 258 eyes of 129 consecutive patients with hyperopic astigmatism and presbyopia who were treated with LASIK-induced micro-monovision. The CRS-Master software was used to generate ablation profiles for the Carl Zeiss Meditec MEL80 excimer laser. The target refraction was piano for distance eyes (dominant eye) and between -1.00 and -1.50 diopters (D) for near eyes. Patients were followed for 1 year. RESULTS: Mean attempted spherical equivalent refraction (SE) correction was +2.54+/-1.16 D (range: +0.25 to +5.75 D). Mean attempted cylinder was -0.52+/-0.49 D (range: -0.00 to -3.25 D). Median age was 56 years (range: 44 to 66 years). Median follow-up was 12.5 months (range: 3.3 months [early retreatment] to 18.2 months). The retreatment rate was 22%. Outcome measures after all treatments were as follows. Mean deviation from the intended SE correction was +0.09+/-0.48 D, with 79% of eyes within +/-0.50 D and 95% within +/-1.00 D. The cylinder correction ratio was 1.23+/-0.63 and the error ratio was 0.67+/-0.65. Of the distance eyes, 86% achieved uncorrected visual acuity of 20/20 and 100% achieved 20/40. Binocularly, 95% of patients achieved 20/20 and 100% achieved 20/40. Eighty-one percent of patients could read J2 and 100% could read J5. Binocularly, 95% of patients achieved 20/20 and could read J5. No eyes lost 2 or more lines of best spectacle-corrected visual acuity. A statistically significant increase was noted in contrast sensitivity at 3 and 6 cycles per degree (cpd), with no reduction at 12 and 18 cpd. The average change in refraction between 3 months and 1 year was +0.11+/-0.36 D with a change of >1.00 D in 2.6% of eyes. CONCLUSIONS: This hyperopic micro-monovision protocol was a well-tolerated and effective procedure for treating patients with presbyopia in moderate to high hyperopia with corrections ranging up to +5.75 D. Contrast sensitivity was improved and the distance vision of near eyes was found to contribute positively to binocular distance vision compared to distance eyes monocularly.

On the origin of the functional architecture of the cortex.

The basic structure of receptive fields and functional maps in primary visual cortex is established without exposure to normal sensory experience and before the onset of the critical period. How the brain wires these circuits in the early stages of development remains unknown. Possible explanations include activity-dependent mechanisms driven by spontaneous activity in the retina and thalamus, and molecular guidance orchestrating thalamo-cortical connections on a fine spatial scale. Here I propose an alternative hypothesis: the blueprint for receptive fields, feature maps, and their inter-relationships may reside in the layout of the retinal ganglion cell mosaics along with a simple statistical connectivity scheme dictating the wiring between thalamus and cortex. The model is shown to account for a number of experimental findings, including the relationship between retinotopy, orientation maps, spatial frequency maps and cytochrome oxidase patches. The theory's simplicity, explanatory and predictive power makes it a serious candidate for the origin of the functional architecture of primary visual cortex.

Distribution of calbindin-28kD and parvalbumin in V1 in normal adult Cebus apella monkeys and in monkeys with retinal lesions.

Several proteins have their normal patterns of distributions altered by monocular visual deprivation. We studied the distribution of the calcium-binding proteins calbindin-28kD (Cb) and parvalbumin (Pv) in V1 in normal adult Cebus apella monkeys and in monkeys with monocular retinal lesions. In normal monkeys, the interblobs regions in layers 2/3 and the layer 4B are intensely labeled for Cb, while Pv reaction showed a complementary labeling pattern with a stronger staining in layers 4A, 4C and in the blob regions in layers 2/3. In monkeys with monocular retinal lesion, the laminar distribution of these proteins was differentially affected, although both reactions resulted in stronger labeling in non-deprived ocular dominance columns. While Cb reaction resulted in stronger labeling in layers 1 through 5, Pv labeling was heavier in layers 2/3, 4A and 4C. There was a clear reduction in the intensity of neuropil staining for both Pv and Cb in deprived ocular dominance columns with little or no reduction in number of labeled cells. This reduction could thus be attributed to activity-dependent changes at synapses level.

Columnar architecture sculpted by GABA circuits in developing cat visual cortex.

The mammalian visual cortex is organized into columns. Here, we examine cortical influences upon developing visual afferents in the cat by altering intrinsic gamma-aminobutyric acid (GABA)-mediated inhibition with benzodiazepines. Local enhancement by agonist (diazepam) infusion did not perturb visual responsiveness, but did widen column spacing. An inverse agonist (DMCM) produced the opposite effect. Thus, intracortical inhibitory circuits shape the geometry of incoming thalamic arbors, suggesting that cortical columnar architecture depends on neuronal activity.

Effects of the Amazonian psychoactive beverage Ayahuasca on binocular rivalry: interhemispheric switching or interhemispheric fusion?

An early theoretical analysis supposed changes in hemispheric integration as the basis of altered state of consciousness induced by psychoactive drugs. Brain imaging studies revealed right cortical activation after administration of hallucinogens. Recent studies on binocular rivalry suggest that interhemispheric switching is the neural substrate of the perceptual oscillations observed during dichoptic stimulus presentation. The current study tested perceptual alternation in ceremonial participants, who ingested the South American hallucinogenic beverage ayahuasca, to examine the claim that there might be changes in interhemispheric function under the influence of hallucinogens. Ingestion of ayahuasca resulted in a decrease of rivalry alternation rates, increased length of one percept and there was evidence of phenomenal fusion. The findings are in line with results of brain activation studies and support the concept of interhemispheric fusion in altered states of consciousness.

Blockade of cyclic AMP-dependent protein kinase does not prevent the reverse ocular dominance shift in kitten visual cortex.

Monocular deprivation (MD) during the critical period for the development of visual cortex causes a loss of binocular response of neurons and a shift to the open eye, a normal ocular dominance (OD) shift. However, when MD is combined with chronic inactivation of the visual cortex by muscimol, the OD distribution of the neurons shifts to the deprived eye (reverse OD shift). We have previously shown that the normal OD shift is abolished by chronic infusion of the protein kinase A (PKA) inhibitor, 8-chloroadenosine-3', 5'-cyclic monophosphorothioate, Rp-isomer (Rp-8-Cl-cAMPS), into kitten visual cortex. In this study, we investigated the effect of this inhibitor on the reverse OD shift. Combination of MD and muscimol infusion into the visual cortex of 6-wk-old kittens caused a reverse OD shift that was comparable to that seen in previous studies. However, a reverse OD shift was also seen with concurrent infusion of the PKA inhibitor with muscimol. The strongest OD shift was observed in layer IV regardless of the presence or absence of the PKA inhibitor. This suggests that the dissociation of pre- and postsynaptic activities, which occurs mainly at thalamocortical synapses, induces the reverse OD shift and that inhibition of PKA does not prevent it. Presumably, an inhibition of PKA has no effect in silent cortex. We conclude that 1) an activation of PKA is not required for the induction of the reverse OD shift, and 2) the intracellular signaling mechanism underlying MD-induced OD plasticity differs between normal and reverse OD shifts.

Visual-ocular motor activity in the macaque pregeniculate complex.

The anatomical connections of the pregeniculate complex (PrGC) with components of the visual-ocular motor system suggested its contribution to ocular motor behavior. Subsequent studies reported saccade-related activity in the primate PrGC. To determine its contribution, we characterized pregeniculate units (n = 128) in alert macaques during ocular motor tasks and visual stimulation. We found that 36/109 saccade-related units exhibited postsaccadic bursts or pauses in tonic discharge for saccades of any amplitude or direction. In contrast to previous results, 46/109 responses preceded or coincided with the saccade, while 47/109 responses were directionally tuned. Pregeniculate units were modulated not only in association with saccades (109/128) but also with smooth eye movements and visual motion (20/128) or eye position (23/128). Multiple ocular motor signals were recorded from 19% of the units, indicating signal convergence on individual neurons. Visual responses were demonstrated in 51% of PrGC units: visual field illumination modulated the resting discharge of 33 units; the responses of 37 saccade-related units and all 23 position-dependent units were modulated by visual stimulation. Early saccadic activity in the PrGC suggests that it contributes more to gaze than postsaccadic modulation of visual or ocular motor activity. The patterns of saccadic responses and the modulation of PrGC activity in association with a variety of visual-ocular motor behaviors suggest its potential role as a relay between the parietal cortex and elements of the brain stem ocular motor pathways, such as the superior colliculus and pretectal nucleus of the optic tract.

Development of cortical circuits: lessons from ocular dominance columns.

The development of ocular dominance columns has served as a Rosetta stone for understanding the mechanisms that guide the construction of cortical circuits. Traditionally, the emergence of ocular dominance columns was thought to be closely tied to the critical period, during which columnar architecture is highly susceptible to alterations in visual input. However, recent findings in cats, monkeys and ferrets indicate that columns develop far earlier, more rapidly and with considerably greater precision than was previously suspected. These observations indicate that the initial establishment of cortical functional architecture, and its subsequent plasticity during the critical period, are distinct developmental phases that might reflect distinct mechanisms.