A laminar model for the joint development of ocular dominance columns and CO blobs in the primary visual cortex.

In this paper, we present a multi-layer, activity-dependent model for the joint development of ocular dominance (OD) columns and cytochrome oxidase (CO) blobs in primate V1. For simplicity, we focus on layers 4C and 2/3 with both layers receiving direct thalamic inputs and layer 4C sending vertical projections to layer 2/3. Both the thalamic and the vertical connections are taken to be modifiable by activity. Using a correlation-based Hebbian learning rule with subtractive normalization, we show how the formation of an OD map in layer 4C is inherited by layer 2/3 via the vertical projections. Competition between these feedforward projections and the direct thalamic input to layer 2/3 then results in the formation of CO blobs superimposed upon the ocular dominance map. The spacing of the OD columns is determined by the spatial profile of the intralaminar connections within layer 4, while the spacing of CO blobs depends both on the width of the OD columns inherited from layer 4 and the spatial distribution of intralaminar connections within the superficial layer. The resulting CO blob distribution is shown to be consistent with experimental data. In addition, we numerically simulate monocular deprivation and find that while the CO blob distribution is unaltered, the OD pattern undergoes modification. The OD stripes of the deprived eye narrow, whereas the OD stripes for the remaining open eye widen.

C1q and SRPX2 regulate microglia mediated synapse elimination during early development in the visual thalamus but not the visual cortex.

The classical complement cascade mediates synapse elimination in the visual thalamus during early brain development. However, whether the primary visual cortex also undergoes complement-mediated synapse elimination during early visual system development remains unknown. Here, we examined microglia-mediated synapse elimination in the visual thalamus and the primary visual cortex of early postnatal C1q and SRPX2 knockout mice. In the lateral geniculate nucleus, deletion of C1q caused a persistent decrease in synapse elimination and microglial synapse engulfment, while deletion of SRPX2 caused a transient increase in the same readouts. In the C1q-SRPX2 double knockout mice, the C1q knockout phenotypes were dominant over the SRPX2 knockout phenotypes, a result which is consistent with SRPX2 being an inhibitor of C1q. We found that genetic deletion of either C1q or SRPX2 did not affect synapse elimination or microglial engulfment of synapses in layer 4 of the primary visual cortex in early brain development. Together, these results show that the classical complement pathway regulates microglia-mediated synapse elimination in the visual thalamus but not the visual cortex during early development of the central nervous system.

Single-cell and single-nucleus RNA-seq uncovers shared and distinct axes of variation in dorsal LGN neurons in mice, non-human primates, and humans.

Abundant evidence supports the presence of at least three distinct types of thalamocortical (TC) neurons in the primate dorsal lateral geniculate nucleus (dLGN) of the thalamus, the brain region that conveys visual information from the retina to the primary visual cortex (V1). Different types of TC neurons in mice, humans, and macaques have distinct morphologies, distinct connectivity patterns, and convey different aspects of visual information to the cortex. To investigate the molecular underpinnings of these cell types, and how these relate to differences in dLGN between human, macaque, and mice, we profiled gene expression in single nuclei and cells using RNA-sequencing. These efforts identified four distinct types of TC neurons in the primate dLGN: magnocellular (M) neurons, parvocellular (P) neurons, and two types of koniocellular (K) neurons. Despite extensively documented morphological and physiological differences between M and P neurons, we identified few genes with significant differential expression between transcriptomic cell types corresponding to these two neuronal populations. Likewise, the dominant feature of TC neurons of the adult mouse dLGN is high transcriptomic similarity, with an axis of heterogeneity that aligns with core vs. shell portions of mouse dLGN. Together, these data show that transcriptomic differences between principal cell types in the mature mammalian dLGN are subtle relative to the observed differences in morphology and cortical projection targets. Finally, alignment of transcriptome profiles across species highlights expanded diversity of GABAergic neurons in primate versus mouse dLGN and homologous types of TC neurons in primates that are distinct from TC neurons in mouse.

No balance between glutamate+glutamine and GABA+ in visual or motor cortices of the human brain: A magnetic resonance spectroscopy study.

Theoretical work, supported by electrophysiological evidence, asserts that a balance between excitation and inhibition (E/I) is critical for healthy brain function. In magnetic resonance spectroscopy (MRS) studies, the ratio of excitatory (glutamate) and inhibitory (γ-aminobutyric acid, GABA) neurotransmitters is often used as a proxy for this E/I balance. Recent MRS work found a positive correlation between GABA+ and Glx (glutamate+glutamine) in medial parietal cortex, providing validation for this proxy and supporting the link between the E/I balance observed in electrophysiology and that detected with MRS. Here we assess the same relationship, between GABA+ and Glx, in visual and motor cortices of male and female human participants. We find moderate to strong evidence that there is no positive correlation between these neurotransmitters in either location. We show this holds true when controlling for a range of other factors (i.e., demographics, signal quality, tissue composition, other neurochemicals) and regardless of the state of neural activity (i.e., resting/active). These results show that there is no brain-wide balance between excitatory and inhibitory neurotransmitters and indicates a dissociation between the E/I balance observed in electrophysiological work and the ratio of MRS-detected neurotransmitters.

Visual cortex cTBS increases mixed percept duration while a-tDCS has no effect on binocular rivalry.

Neuromodulation of the primary visual cortex using anodal transcranial direct current stimulation (a-tDCS) can alter visual perception and enhance neuroplasticity. However, the mechanisms that underpin these effects are currently unknown. When applied to the motor cortex, a-tDCS reduces the concentration of the inhibitory neurotransmitter gamma aminobutyric acid (GABA), an effect that has been linked to increased neuroplasticity. The aim of this study was to assess whether a-tDCS also reduces GABA-mediated inhibition when applied to the human visual cortex. Changes in visual cortex inhibition were measured using the mixed percept duration in binocular rivalry. Binocular rivalry mixed percept duration has recently been advocated as a direct and sensitive measure of visual cortex inhibition whereby GABA agonists decrease mixed percept durations and agonists of the excitatory neurotransmitter acetylcholine (ACH) increase them. Our hypothesis was that visual cortex a-tDCS would increase mixed percept duration by reducing GABA-mediated inhibition and increasing cortical excitation. In addition, we measured the effect of continuous theta-burst transcranial magnetic stimulation (cTBS) of the visual cortex on binocular rivalry dynamics. When applied to the motor or visual cortex, cTBS increases GABA concentration and we therefore hypothesized that visual cortex cTBS would decrease the mixed percept duration. Binocular rivalry dynamics were recorded before and after active and sham a-tDCS (N = 15) or cTBS (N = 15). Contrary to our hypotheses, a-tDCS had no effect, whereas cTBS increased mixed percepts during rivalry. These results suggest that the neurochemical mechanisms of a-tDCS may differ between the motor and visual cortices.

Methods for quantitative susceptibility and R2* mapping in whole post-mortem brains at 7T applied to amyotrophic lateral sclerosis.

Susceptibility weighted magnetic resonance imaging (MRI) is sensitive to the local concentration of iron and myelin. Here, we describe a robust image processing pipeline for quantitative susceptibility mapping (QSM) and R2* mapping of fixed post-mortem, whole-brain data. Using this pipeline, we compare the resulting quantitative maps in brains from patients with amyotrophic lateral sclerosis (ALS) and controls, with validation against iron and myelin histology. Twelve post-mortem brains were scanned with a multi-echo gradient echo sequence at 7T, from which susceptibility and R2* maps were generated. Semi-quantitative histological analysis for ferritin (the principal iron storage protein) and myelin proteolipid protein was performed in the primary motor, anterior cingulate and visual cortices. Magnetic susceptibility and R2* values in primary motor cortex were higher in ALS compared to control brains. Magnetic susceptibility and R2* showed positive correlations with both myelin and ferritin estimates from histology. Four out of nine ALS brains exhibited clearly visible hyperintense susceptibility and R2* values in the primary motor cortex. Our results demonstrate the potential for MRI-histology studies in whole, fixed post-mortem brains to investigate the biophysical source of susceptibility weighted MRI signals in neurodegenerative diseases like ALS.

Functional ultrasound imaging to study brain dynamics: Application of pharmaco-fUS to atomoxetine.

Functional ultrasound (fUS) is a new tool enabling the imaging of brain activity through the regional monitoring of cerebral blood volume (CBV) dynamics. This innovative technique has not yet demonstrated its full potential in pharmacological applications and drug development. In the current proof-of-concept study, the impact of atomoxetine (ATX), a potent norepinephrine reuptake inhibitor and non-stimulant treatment marketed in attention-deficit/hyperactivity-disorder, was evaluated in anesthetized rat using pharmacological functional ultrasound (pharmaco-fUS) at increasing doses (0.3, 1 and 3 mg/kg). Using regions of interest (acute changes of CBV and functional connectivity) or pixel-based (general linear modeling and independent component analysis) analysis, we here demonstrated that ATX consistently displayed a hemodynamic effect in the visual cortex, the dentate gyrus and thalamus, especially visual areas such as lateral posterior thalamic nuclei and lateral geniculate nuclei (LGN). The time profile of ATX effects was dose-dependent, with fastest CBV increases at the highest dose, and longer CBV increases at the intermediate dose. Standardizing the use of pharmaco-fUS could improve our understanding of the mechanism of action of drugs active in the brain and might constitute a new step to move forward in drug development for neurological disorders.

Brain activity regulates loose coupling between mitochondrial and cytosolic Ca2+ transients.

Mitochondrial calcium ([Ca2+]mito) dynamics plays vital roles in regulating fundamental cellular and organellar functions including bioenergetics. However, neuronal [Ca2+]mito dynamics in vivo and its regulation by brain activity are largely unknown. By performing two-photon Ca2+ imaging in the primary motor (M1) and visual cortexes (V1) of awake behaving mice, we find that discrete [Ca2+]mito transients occur synchronously over somatic and dendritic mitochondrial network, and couple with cytosolic calcium ([Ca2+]cyto) transients in a probabilistic, rather than deterministic manner. The amplitude, duration, and frequency of [Ca2+]cyto transients constitute important determinants of the coupling, and the coupling fidelity is greatly increased during treadmill running (in M1 neurons) and visual stimulation (in V1 neurons). Moreover, Ca2+/calmodulin kinase II is mechanistically involved in modulating the dynamic coupling process. Thus, activity-dependent dynamic [Ca2+]mito-to-[Ca2+]cyto coupling affords an important mechanism whereby [Ca2+]mito decodes brain activity for the regulation of mitochondrial bioenergetics to meet fluctuating neuronal energy demands as well as for neuronal information processing.

Glucose hypometabolism in the visual cortex proportional to disease severity in patients with essential blepharospasm.

Essential blepharospasm (EB) causes difficulty in eyelid opening because of involuntary movements of the orbicularis oculi muscle. Patients with EB have functional visual loss due to sustained eyelid closure. We examined cerebral glucose metabolism in 39 patients with EB (12 men and 27 women; mean age, 52.1 years) by using positron emission tomography with 18F-fluorodeoxyglucose. Forty-eight eye open healthy subjects and 48 eye close healthy subjects served as controls. We analyzed and compared the data between the patients and controls by using both statistical parametric mapping (SPM) and regions of interest (ROIs). We defined ROIs on both sides of the posterior striate cortex, anterior striate cortex, extrastriate cortex, and thalamus. In SPM analysis, glucose hypometabolism were observed in both sides of the extrastriate cortex compared to eye open controls but not to eye close controls. We also observed a significant negative correlation between the Jankovic Rating Scale (JRS) sum score and relative glucose metabolism level in the striate cortex of these patients. ROI analysis, a significant correlation was observed between the JRS sum score and glucose metabolism level in the posterior (right: r = -0.53, P = .0005; left: r = -0.65, P = .00001) and anterior (right: r = -0.33, P = .04; left: r = -0.37, P = .02) striate cortices of patients with EB. We surmise that the interruption of visual input cause glucose hypometabolism in the visual cortex of patients with EB.

Wide and Deep Imaging of Neuronal Activities by a Wearable NeuroImager Reveals Premotor Activity in the Whole Motor Cortex.

Wearable technologies for functional whole brain imaging in freely moving animals would advance our understanding of cognitive processing and adaptive behavior. Fluorescence imaging can visualize the activity of individual neurons in real time, but conventional microscopes have limited sample coverage in both the width and depth of view. Here we developed a novel head-mounted laser camera (HLC) with macro and deep-focus lenses that enable fluorescence imaging at cellular resolution for comprehensive imaging in mice expressing a layer- and cell type-specific calcium probe. We visualized orientation selectivity in individual excitatory neurons across the whole visual cortex of one hemisphere, and cell assembly expressing the premotor activity that precedes voluntary movement across the motor cortex of both hemispheres. Including options for multiplex and wireless interfaces, our wearable, wide- and deep-imaging HLC technology could enable simple and economical mapping of neuronal populations underlying cognition and behavior.

Preclinical tissue distribution and metabolic correlations of vigabatrin, an antiepileptic drug associated with potential use-limiting visual field defects.

Vigabatrin (VGB; (S)-(+)/(R)-(-) 4-aminohex-5-enoic acid), an antiepileptic irreversibly inactivating GABA transaminase (GABA-T), manifests use-limiting ocular toxicity. Hypothesizing that the active S enantiomer of VGB would preferentially accumulate in eye and visual cortex (VC) as one potential mechanism for ocular toxicity, we infused racemic VGB into mice via subcutaneous minipump at 35, 70, and 140 mg/kg/d (n = 6-8 animals/dose) for 12 days. VGB enantiomers, total GABA and ß-alanine (BALA), 4-guanidinobutyrate (4-GBA), and creatine were quantified by mass spectrometry in eye, brain, liver, prefrontal cortex (PFC), and VC. Plasma VGB concentrations increased linearly by dose (3 ± 0.76 (35 mg/kg/d); 15.1 ± 1.4 (70 mg/kg/d); 34.6 ± 3.2 µmol/L (140 mg/kg/d); mean ± SEM) with an S/R ratio of 0.74 ± 0.02 (n = 14). Steady state S/R ratios (35, 70 mg/kg/d doses) were highest in eye (5.5 ± 0.2; P < 0.0001), followed by VC (3.9 ± 0.4), PFC (3.6 ± 0.3), liver (2.9 ± 0.1), and brain (1.5 ± 0.1; n = 13-14 each). Total VGB content of eye exceeded that of brain, PFC and VC at all doses. High-dose VGB diminished endogenous metabolite production, especially in PFC and VC. GABA significantly increased in all tissues (all doses) except brain; BALA increases were confined to liver and VC; and 4-GBA was prominently increased in brain, PFC and VC (and eye at high dose). Linear correlations between enantiomers and GABA were observed in all tissues, but only in PFC/VC for BALA, 4-GBA, and creatine. Preferential accumulation of the VGB S isomer in eye and VC may provide new insight into VGB ocular toxicity.

Synapse-Selective Control of Cortical Maturation and Plasticity by Parvalbumin-Autonomous Action of SynCAM 1.

Cortical plasticity peaks early in life and tapers in adulthood, as exemplified in the primary visual cortex (V1), wherein brief loss of vision in one eye reduces cortical responses to inputs from that eye during the critical period but not in adulthood. The synaptic locus of cortical plasticity and the cell-autonomous synaptic factors determining critical periods remain unclear. We here demonstrate that the immunoglobulin protein Synaptic Cell Adhesion Molecule 1 (SynCAM 1/Cadm1) is regulated by visual experience and limits V1 plasticity. Loss of SynCAM 1 selectively reduces the number of thalamocortical inputs onto parvalbumin (PV+) interneurons, impairing the maturation of feedforward inhibition in V1. SynCAM 1 acts in PV+ interneurons to actively restrict cortical plasticity, and brief PV+-specific knockdown of SynCAM 1 in adult visual cortex restores juvenile-like plasticity. These results identify a synapse-specific, cell-autonomous mechanism for thalamocortical visual circuit maturation and closure of the visual critical period.

Shared and distinct transcriptomic cell types across neocortical areas.

The neocortex contains a multitude of cell types that are segregated into layers and functionally distinct areas. To investigate the diversity of cell types across the mouse neocortex, here we analysed 23,822 cells from two areas at distant poles of the mouse neocortex: the primary visual cortex and the anterior lateral motor cortex. We define 133 transcriptomic cell types by deep, single-cell RNA sequencing. Nearly all types of GABA (γ-aminobutyric acid)-containing neurons are shared across both areas, whereas most types of glutamatergic neurons were found in one of the two areas. By combining single-cell RNA sequencing and retrograde labelling, we match transcriptomic types of glutamatergic neurons to their long-range projection specificity. Our study establishes a combined transcriptomic and projectional taxonomy of cortical cell types from functionally distinct areas of the adult mouse cortex.

Functional energetic responses and individual variance of the human brain revealed by quantitative imaging of adenosine triphosphate production rates.

Cellular ATP energy metabolism and regulation are essential for brain function and health. Given the high ATP expenditure at resting-state, it is not yet clear how the human brain at working-state can effectively regulate ATP production to meet higher energy requirement. Through quantitative measurement of regional cerebral ATP production rates and associated neurophysiological parameters in human visual cortex at rest and during visual stimulation, we found significant stimulus-induced and highly correlated neuroenergetic changes, indicating distinctive and complementary roles of the ATP synthesis reactions in supporting evoked neuronal activity and maintaining ATP homeostasis. We also uncovered large individual variances in the neuroenergetic responses and significant reductions in intracellular [H+] and free [Mg2+] during the stimulation. These results provide new insights into the mechanism underlying the brain ATP energy regulation and present a sensitive and much-needed neuroimaging tool for quantitatively assessing neuroenergetic state in healthy and diseased human brain.

Neuroprotective effect of fermented papaya preparation by activation of Nrf2 pathway in astrocytes.

OBJECTIVES: Nuclear factor erythroid 2-related factor (Nrf2) in astrocyte plays important roles in brain homeostasis. Fermented papaya preparation (FPP) has anti-oxidative, anti-inflammatory, immunoregulatory properties. The present study investigated the effects of FPP on activation of Nrf2 and release of Nrf2-regulated neuroprotective antioxidants and detoxifying molecules. METHODS: Primary cultured astrocytes from rat embryos were treated with FPP for 6 or 24 hours. The expression levels of nuclear Nrf2 and cytoplasmic Nrf2-regulated molecules were determined by western blot analysis and immunohistochemistry. Glutathione levels were measured in cells and medium. Dopaminergic neurons were exposed 6-hydroxydopamine (6-OHDA) with/without pre-treatment with FPP astrocytes. Mice were treated orally with FPP for 2 weeks. RESULTS: FPP increased nuclear translocation of Nrf2 in striatal astrocytes, induced up-regulation of NAD(P)H quinine oxidoreductase-1, glutathione-S transferase and hemeoxygenase-1, and increased glutathione level and the percentage of metallothionein-expressing astrocytes. Moreover, FPP suppressed 6-OHDA-induced dopaminergic neuronal loss in not only neuron-astrocyte mixed culture, but also neuron-rich cultures pre-treated with glial conditioned medium. Two-week oral treatment of mice with FPP resulted in Nrf2 activation and increase in glutathione level in striatum. DISCUSSION: The results indicated that FPP enhances the anti-oxidative capacity through activation of Nrf2 in astrocytes, suggesting it may provide neuroprotection in oxidative stress-related neurodegenerative diseases.

The serotonin hallucinogen 5-MeO-DMT alters cortico-thalamic activity in freely moving mice: Regionally-selective involvement of 5-HT1A and 5-HT2A receptors.

5-MeO-DMT is a natural hallucinogen acting as serotonin 5-HT1A/5-HT2A receptor agonist. Its ability to evoke hallucinations could be used to study the neurobiology of psychotic symptoms and to identify new treatment targets. Moreover, recent studies revealed the therapeutic potential of serotonin hallucinogens in treating mood and anxiety disorders. Our previous results in anesthetized animals show that 5-MeO-DMT alters cortical activity via 5-HT1A and 5-HT2A receptors. Here, we examined 5-MeO-DMT effects on oscillatory activity in prefrontal (PFC) and visual (V1) cortices, and in mediodorsal thalamus (MD) of freely-moving wild-type (WT) and 5-HT2A-R knockout (KO2A) mice. We performed local field potential multi-recordings evaluating the power at different frequency bands and coherence between areas. We also examined the prevention of 5-MeO-DMT effects by the 5-HT1A-R antagonist WAY-100635. 5-MeO-DMT affected oscillatory activity more in cortical than in thalamic areas. More marked effects were observed in delta power in V1 of KO2A mice. 5-MeO-DMT increased beta band coherence between all examined areas. In KO2A mice, WAY100635 prevented most of 5-MeO-DMT effects on oscillatory activity. The present results indicate that hallucinatory activity of 5-MeO-DMT is likely mediated by simultaneous alteration of prefrontal and visual activities. The prevention of these effects by WAY-100635 in KO2A mice supports the potential usefulness of 5-HT1A receptor antagonists to treat visual hallucinations. 5-MeO-DMT effects on PFC theta activity and cortico-thalamic coherence may be related to its antidepressant activity. This article is part of the Special Issue entitled 'Psychedelics: New Doors, Altered Perceptions'.

Visual cortex and auditory cortex activation in early binocularly blind macaques: A BOLD-fMRI study using auditory stimuli.

Cross-modal plasticity within the visual and auditory cortices of early binocularly blind macaques is not well studied. In this study, four healthy neonatal macaques were assigned to group A (control group) or group B (binocularly blind group). Sixteen months later, blood oxygenation level-dependent functional imaging (BOLD-fMRI) was conducted to examine the activation in the visual and auditory cortices of each macaque while being tested using pure tones as auditory stimuli. The changes in the BOLD response in the visual and auditory cortices of all macaques were compared with immunofluorescence staining findings. Compared with group A, greater BOLD activity was observed in the bilateral visual cortices of group B, and this effect was particularly obvious in the right visual cortex. In addition, more activated volumes were found in the bilateral auditory cortices of group B than of group A, especially in the right auditory cortex. These findings were consistent with the fact that there were more c-Fos-positive cells in the bilateral visual and auditory cortices of group B compared with group A (p < 0.05). In conclusion, the bilateral visual cortices of binocularly blind macaques can be reorganized to process auditory stimuli after visual deprivation, and this effect is more obvious in the right than the left visual cortex. These results indicate the establishment of cross-modal plasticity within the visual and auditory cortices.

Optic nerve, superior colliculus, visual thalamus, and primary visual cortex of the northern elephant seal (Mirounga angustirostris) and California sea lion (Zalophus californianus).

The northern elephant seal (Mirounga angustirostris) and California sea lion (Zalophus californianus) are members of a diverse clade of carnivorous mammals known as pinnipeds. Pinnipeds are notable for their large, ape-sized brains, yet little is known about their central nervous system. Both the northern elephant seal and California sea lion spend most of their lives at sea, but each also spends time on land to breed and give birth. These unique coastal niches may be reflected in specific evolutionary adaptations to their sensory systems. Here, we report on components of the visual pathway in these two species. We found evidence for two classes of myelinated fibers within the pinniped optic nerve, those with thick myelin sheaths (elephant seal: 9%, sea lion: 7%) and thin myelin sheaths (elephant seal: 91%, sea lion: 93%). In order to investigate the architecture of the lateral geniculate nucleus, superior colliculus, and primary visual cortex, we processed brain sections from seal and sea lion pups for Nissl substance, cytochrome oxidase, and vesicular glutamate transporters. As in other carnivores, the dorsal lateral geniculate nucleus consisted of three main layers, A, A1, and C, while each superior colliculus similarly consisted of seven distinct layers. The sea lion visual cortex is located at the posterior side of cortex between the upper and lower banks of the postlateral sulcus, while the elephant seal visual cortex extends far more anteriorly along the dorsal surface and medial wall. These results are relevant to comparative studies related to the evolution of large brains.

Enhanced visual adaptation in cochlear implant users revealed by concurrent EEG-fNIRS.

Previous studies have observed lower visual cortex activation for visual processing in cochlear implant (CI) users compared to normal hearing controls, while others reported enhanced visual speechreading abilities in CI users. The present work investigated whether lower visual cortical activation for visual processing can be explained by a more efficient visual sensory encoding in CI users. Specifically, we investigated whether CI users show enhanced stimulus-specific adaptation for visual stimuli compared to controls. Auditory sensory adaptation was also investigated to explore the sensory specificity of the predicted effect. Twenty post-lingually deafened adult CI users and twenty age-matched controls were presented with repeated visual and auditory stimuli during simultaneous acquisition of electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS). By integrating EEG and fNIRS signals we found significantly enhanced visual adaptation and lower visual cortex activation in CI users compared to controls. That is, responses to repeated visual stimuli decreased more prominently in CI users than in controls. The results suggest that CI users process visual stimuli more efficiently than controls.

Structural organization of the dendritic reticulum linked by gap junctions in layer 4 of the visual cortex.

Neuronal gap junctions are ubiquitous in the brain, but their precise positions in actual neuronal circuits have been uncertain, and their functional roles remain unclear. In this study, I visualized connexin36-immunoreactive gap junctions and examined the structural features of the interconnected dendrites arising from parvalbumin (PV)-positive interneurons in layer 4 of the feline visual cortex. I observed evidence for net-like dense linkages of dendrites among virtually all PV neurons (56/58 cells, 96.6%) in the tissue. This dendritic reticulum established connections among clustered cells and further among remote cells. The latter connectivity exhibited a preference for vertical direction, including translaminar linkages, but was also characterized by lateral continuity. Measurement of the distances from each dendritic gap junction back to the two connected somata revealed that at least one of two somata was within 50µm from the junction in 77.5% of the cases and within 75µm in 91.2% of the cases. Thus, distal gap junctions mediated morphologically asymmetrical connection where one soma was close to, but the other soma was far from the connecting junction. This connectivity was typically observed between neurons located apart in the same columnar space, where a long vertical dendrite bridged two neurons through an asymmetrically positioned gap junction. In contrast, gap junctions formed between nearby cells were close to both somata. Thalamocortical afferents established synapses densely on somata of layer 4 PV neurons, indicating the possible involvement of proximal gap junctions in visual stimulus-driven feedforward regulation. These findings provide a new structural basis for cortical investigations.