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Inhibition in thalamorecipient layer 4 simple cells of primary visual cortex is believed to play important roles in establishing visual response properties and integrating visual inputs across their receptive fields (RFs). Simple cell RFs are characterized by nonoverlapping, spatially restricted subregions in which visual stimuli can either increase or decrease the firing rate of the cell, depending on contrast. Inhibition is believed to be triggered exclusively from visual stimulation of individual RF subregions. However, this view is at odds with the known anatomy of layer 4 interneurons in visual cortex and differs from recent findings in mouse visual cortex. Here we show with in vivo intracellular recordings in cats that while excitation is restricted to RF subregions, inhibition spans the width of simple cell RFs. Consequently, excitatory stimuli within a subregion concomitantly drive excitation and inhibition. Furthermore, we found that the distribution of inhibition across the RF is stronger toward OFF subregions. This inhibitory OFF-subregion bias has a functional consequence on spatial integration of inputs across the RF. A model based on the known anatomy of layer 4 demonstrates that the known proportion and connectivity of inhibitory neurons in layer 4 of primary visual cortex is sufficient to explain broad inhibition with an OFF-subregion bias while generating a variety of phase relations, including antiphase, between excitation and inhibition in response to drifting gratings. SIGNIFICANCE STATEMENT The wiring of excitatory and inhibitory neurons in cortical circuits is key to determining the response properties in sensory cortex. In the visual cortex, the first cells that receive visual input are simple cells in layer 4. The underlying circuitry responsible for the response properties of simple cells is not yet known. In this study, we challenge a long-held view concerning the pattern of inhibitory input and provide results that agree with current known anatomy. We show here that inhibition is evoked broadly across the receptive fields of simple cells, and we identify a surprising bias in inhibition within the receptive field. Our findings represent a step toward a unified view of inhibition across different species and sensory systems., (Copyright © 2018 the authors 0270-6474/18/380595-18$15.00/0.)

Seminal studies of the thalamocortical circuit in the visual system of the cat have been central to our understanding of sensory encoding. However, thalamocortical synaptic properties remain poorly understood. We used paired recordings, in the lateral geniculate nucleus (LGN) and primary visual cortex (V1), to provide the first in vivo characterization of sensory-driven thalamocortical potentials in V1. The amplitudes of EPSPs we characterized were smaller than those previously reported in vitro Consistent with prior findings, connected LGN-V1 pairs were only found when their receptive fields (RFs) overlapped, and the probability of connection increased steeply with degree of RF overlap and response similarity. However, surprisingly, we found no relationship between EPSP amplitudes and the similarity of RFs or responses, suggesting different connectivity models for intracortical and thalamocortical circuits. Putative excitatory regular-spiking (RS) and inhibitory fast-spiking (FS) V1 cells had similar EPSP characteristics, showing that in the visual system, feedforward excitation and inhibition are driven with equal strength by the thalamus. Similar to observations in the somatosensory cortex, FS V1 cells received less specific input from LGN. Finally, orientation tuning in V1 was not inherited from single presynaptic LGN cells, suggesting that it must emerge exclusively from the combined input of all presynaptic LGN cells. Our results help to decipher early visual encoding circuits and have immediate utility in providing physiological constraints to computational models of the visual system. SIGNIFICANCE STATEMENT To understand how the brain encodes the visual environment, we must understand the transfer of visual signals between various regions of the brain. Therefore, understanding synaptic dynamics is critical to our understanding of sensory encoding. This study provides the first characterization of visually evoked synaptic potentials between the visual thalamus and visual cortex in an intact animal. To record these potentials, we simultaneously recorded the extracellular potential of presynaptic thalamic cells and the intracellular potential of postsynaptic cortical cells in input layers of primary visual cortex. Our characterization of synaptic potentials in vivo disagreed with prior findings in vitro This study will increase our understanding of thalamocortical circuits and will improve computational models of visual encoding., (Copyright © 2017 the authors 0270-6474/17/375250-13$15.00/0.)

The lateral geniculate nucleus (LGN) contains a unique and numerous class of cells called lagged cells, which introduce a time delay into the neural signal provided to cortex. Previous studies have shown that this delay is dependent on GABA(A) receptors within the LGN. Furthermore, lagged cells have distinct integrative properties with a slower rising, more sustained, and overall lower firing rates than nonlagged cells. We have recorded intracellularly from lagged cells in the cat LGN and found a unique property of their retinal inputs that underlies both their temporal and integrative visual response properties. Lagged cell EPSPs, which often derive from a single retinal input, have smaller amplitudes, repolarize more quickly, and are followed by a Cl(-)-dependent hyperpolarization compared with nonlagged cells. The Cl(-)-dependent hyperpolarization sums early in the visual response generating a powerful synaptic inhibition that coincides with the peak frequency of retinal input and delays the spike response in lagged cells. The hyperpolarization subsides rapidly over ∼20-40 ms allowing for slow summation of the retinal input leading to the visual spike response. Given the tight association of single retinal EPSPs and the following inhibition, we propose that both functional properties result from the triadic circuitry prevalent in the LGN and particularly prominent in lagged X-cells. Thus, our results show for the first time a dynamic interaction of retinal excitation and fast feedforward inhibition that determines the integrative properties and the delay in firing of lagged cells.

Arrays of electrodes for recording and stimulating the brain are used throughout clinical medicine and basic neuroscience research, yet are unable to sample large areas of the brain while maintaining high spatial resolution because of the need to individually wire each passive sensor at the electrode-tissue interface. To overcome this constraint, we developed new devices that integrate ultrathin and flexible silicon nanomembrane transistors into the electrode array, enabling new dense arrays of thousands of amplified and multiplexed sensors that are connected using fewer wires. We used this system to record spatial properties of cat brain activity in vivo, including sleep spindles, single-trial visual evoked responses and electrographic seizures. We found that seizures may manifest as recurrent spiral waves that propagate in the neocortex. The developments reported here herald a new generation of diagnostic and therapeutic brain-machine interface devices.

Electronics that are capable of intimate, non-invasive integration with the soft, curvilinear surfaces of biological tissues offer important opportunities for diagnosing and treating disease and for improving brain/machine interfaces. This article describes a material strategy for a type of bio-interfaced system that relies on ultrathin electronics supported by bioresorbable substrates of silk fibroin. Mounting such devices on tissue and then allowing the silk to dissolve and resorb initiates a spontaneous, conformal wrapping process driven by capillary forces at the biotic/abiotic interface. Specialized mesh designs and ultrathin forms for the electronics ensure minimal stresses on the tissue and highly conformal coverage, even for complex curvilinear surfaces, as confirmed by experimental and theoretical studies. In vivo, neural mapping experiments on feline animal models illustrate one mode of use for this class of technology. These concepts provide new capabilities for implantable and surgical devices.

Zinc is an essential trace element and plays crucial roles in normal development, often as an integral structural component of transcription factors and enzymes. Recent evidence suggests that intracellular Zn(2+) functions as a signaling molecule, mediating a variety of important physiological phenomena. However, the immediate effectors of intracellular Zn(2+) signaling are not well known. We show here that intracellular Zn(2+) potently and reversibly activates large-conductance voltage- and Ca(2+)-activated Slo1 K(+) (BK) channels. The full effect of Zn(2+) requires His(365) in the RCK1 (regulator of conductance for K(+)) domain of the channel. Furthermore, mutation of two nearby acidic residues, Asp(367) and Glu(399), also reduced activation of the channel by Zn(2+), suggesting a possible structural arrangement for Zn(2+) binding by the aforementioned residues. Extracellular Zn(2+) activated Slo1 BK channels when coexpressed with Zn(2+)-permeable TRPM7 (transient receptor potential melastatin 7) channels. The results thus demonstrate that Slo1 BK channels represent a positive and direct effector of Zn(2+) signaling and may participate in sculpting cellular response to an increase in intracellular Zn(2+) concentration.