More than expected: extracellular waveforms and functional responses in monkey LGN.

Unlike the exhaustive determination of cell types in the retina, key populations in the lateral geniculate nucleus of the thalamus (LGN) may have been missed. Here, we have begun to characterize the full range of extracellular neuronal responses in the LGN of awake monkeys using multi-electrodes during the presentation of colored noise visual stimuli to identify any previously overlooked signals. Extracellular spike waveforms of single units were classified into seven distinct classes, revealing previously unrecognized diversity: four negative-dominant classes that were narrow or broad, one triphasic class, and two positive-dominant classes. Based on their mapped receptive field (RF), these units were further categorized into either magnocellular (M), parvocellular (P), koniocellular (K), or non-RF (N). We found correlations between spike shape and mapped RF and response characteristics, with negative and narrow spiking waveform units predominantly associated with P and N RFs, and positive waveforms mostly linked to M RFs. Responses from positive waveforms exhibited shorter latencies, larger RF sizes, and were associated with larger eccentricities in the visual field than the other waveform classes. Additionally, N cells, those without an estimated RF, were consistently responsive to the visually presented mapping stimulus at a lower and more sustained rate than units with an RF. These findings suggest that the LGN cell population may be more diverse than previously believed.

An In Vivo Platform for Rebuilding Functional Neocortical Tissue.

Recent progress in cortical stem cell transplantation has demonstrated its potential to repair the brain. However, current transplant models have yet to demonstrate that the circuitry of transplant-derived neurons can encode useful function to the host. This is likely due to missing cell types within the grafts, abnormal proportions of cell types, abnormal cytoarchitecture, and inefficient vascularization. Here, we devised a transplant platform for testing neocortical tissue prototypes. Dissociated mouse embryonic telencephalic cells in a liquid scaffold were transplanted into aspiration-lesioned adult mouse cortices. The donor neuronal precursors differentiated into upper and deep layer neurons that exhibited synaptic puncta, projected outside of the graft to appropriate brain areas, became electrophysiologically active within one month post-transplant, and responded to visual stimuli. Interneurons and oligodendrocytes were present at normal densities in grafts. Grafts became fully vascularized by one week post-transplant and vessels in grafts were perfused with blood. With this paradigm, we could also organize cells into layers. Overall, we have provided proof of a concept for an in vivo platform that can be used for developing and testing neocortical-like tissue prototypes.

Perceptual learning in a non-human primate model of artificial vision.

Visual perceptual grouping, the process of forming global percepts from discrete elements, is experience-dependent. Here we show that the learning time course in an animal model of artificial vision is predicted primarily from the density of visual elements. Three naïve adult non-human primates were tasked with recognizing the letters of the Roman alphabet presented at variable size and visualized through patterns of discrete visual elements, specifically, simulated phosphenes mimicking a thalamic visual prosthesis. The animals viewed a spatially static letter using a gaze-contingent pattern and then chose, by gaze fixation, between a matching letter and a non-matching distractor. Months of learning were required for the animals to recognize letters using simulated phosphene vision. Learning rates increased in proportion to the mean density of the phosphenes in each pattern. Furthermore, skill acquisition transferred from trained to untrained patterns, not depending on the precise retinal layout of the simulated phosphenes. Taken together, the findings suggest that learning of perceptual grouping in a gaze-contingent visual prosthesis can be described simply by the density of visual activation.

A Device for Long-Term Perfusion, Imaging, and Electrical Interfacing of Brain Tissue In vitro.

Distributed microelectrode array (MEA) recordings from consistent, viable, ≥500 µm thick tissue preparations over time periods from days to weeks may aid in studying a wide range of problems in neurobiology that require in vivo-like organotypic morphology. Existing tools for electrically interfacing with organotypic slices do not address necrosis that inevitably occurs within thick slices with limited diffusion of nutrients and gas, and limited removal of waste. We developed an integrated device that enables long-term maintenance of thick, functionally active, brain tissue models using interstitial perfusion and distributed recordings from thick sections of explanted tissue on a perforated multi-electrode array. This novel device allows for automated culturing, in situ imaging, and extracellular multi-electrode interfacing with brain slices, 3-D cell cultures, and potentially other tissue culture models. The device is economical, easy to assemble, and integrable with standard electrophysiology tools. We found that convective perfusion through the culture thickness provided a functional benefit to the preparations as firing rates were generally higher in perfused cultures compared to their respective unperfused controls. This work is a step toward the development of integrated tools for days-long experiments with more consistent, healthier, thicker, and functionally more active tissue cultures with built-in distributed electrophysiological recording and stimulation functionality. The results may be useful for the study of normal processes, pathological conditions, and drug screening strategies currently hindered by the limitations of acute (a few hours long) brain slice preparations.

Saccade direction encoding in the primate entorhinal cortex during visual exploration.

We recently demonstrated that position in visual space is represented by grid cells in the primate entorhinal cortex (EC), suggesting that visual exploration of complex scenes in primates may employ signaling mechanisms similar to those used during exploration of physical space via movement in rodents. Here, we describe a group of saccade direction (SD) cells that encode eye movement information in the monkey EC during free-viewing of complex images. Significant saccade direction encoding was found in 20% of the cells recorded in the posterior EC. SD cells were generally broadly tuned and two largely separate populations of SD cells encoded future and previous saccade direction. Some properties of these cells resemble those of head-direction cells in rodent EC, suggesting that the same neural circuitry may be capable of performing homologous spatial computations under different exploratory contexts.

Mapping the primate lateral geniculate nucleus: a review of experiments and methods.

Mapping neuronal responses in the lateral geniculate nucleus (LGN) is key to understanding how visual information is processed in the brain. This paper focuses on our current knowledge of the dynamics the receptive field (RF) as broken down into the classical receptive field (CRF) and the extra-classical receptive field (ECRF) in primate LGN. CRFs in the LGN are known to be similar to those in the retinal ganglion cell layer in terms of both spatial and temporal characteristics, leading to the standard interpretation of the LGN as a relay center from retina to primary visual cortex. ECRFs have generally been found to be large and inhibitory, with some differences in magnitude between the magno-, parvo-, and koniocellular pathways. The specific contributions of the retina, thalamus, and visual cortex to LGN ECRF properties are presently unknown. Some reports suggest a retinal origin for extra-classical suppression based on latency arguments and other reports have suggested a thalamic origin for extra-classical suppression. This issue is complicated by the use of anesthetized animals, where cortical activity is likely to be altered. Thus further study of LGN ECRFs is warranted to reconcile these discrepancies. Producing descriptions of RF properties of LGN neurons could be enhanced by employing preferred naturalistic stimuli. Although there has been significant work in cats with natural scene stimuli and noise that statistically imitates natural scenes, we highlight a need for similar data from primates. Obtaining these data may be aided by recent advancements in experimental and analytical techniques that permit the efficient study of nonlinear RF characteristics in addition to traditional linear factors. In light of the reviewed topics, we conclude by suggesting experiments to more clearly elucidate the spatial and temporal structure of ECRFs of primate LGN neurons.

A map of visual space in the primate entorhinal cortex.

Place-modulated activity among neurons in the hippocampal formation presents a means to organize contextual information in the service of memory formation and recall. One particular spatial representation, that of grid cells, has been observed in the entorhinal cortex (EC) of rats and bats, but has yet to be described in single units in primates. Here we examined spatial representations in the EC of head-fixed monkeys performing a free-viewing visual memory task. Individual neurons were identified in the primate EC that emitted action potentials when the monkey fixated multiple discrete locations in the visual field in each of many sequentially presented complex images. These firing fields possessed spatial periodicity similar to a triangular tiling with a corresponding well-defined hexagonal structure in the spatial autocorrelation. Further, these neurons showed theta-band oscillatory activity and changing spatial scale as a function of distance from the rhinal sulcus, which is consistent with previous findings in rodents. These spatial representations may provide a framework to anchor the encoding of stimulus content in a complex visual scene. Together, our results provide a direct demonstration of grid cells in the primate and suggest that EC neurons encode space during visual exploration, even without locomotion.