Higher-order thalamocortical circuits are specified by embryonic cortical progenitor types in the mouse brain.

The sensory cortex receives synaptic inputs from both first-order and higher-order thalamic nuclei. First-order inputs relay simple stimulus properties from the periphery, whereas higher-order inputs relay more complex response properties, provide contextual feedback, and modulate plasticity. Here, we reveal that a cortical neuron's higher-order input is determined by the type of progenitor from which it is derived during embryonic development. Within layer 4 (L4) of the mouse primary somatosensory cortex, neurons derived from intermediate progenitors receive stronger higher-order thalamic input and exhibit greater higher-order sensory responses. These effects result from differences in dendritic morphology and levels of the transcription factor Lhx2, which are specified by the L4 neuron's progenitor type. When this mechanism is disrupted, cortical circuits exhibit altered higher-order responses and sensory-evoked plasticity. Therefore, by following distinct trajectories, progenitor types generate diversity in thalamocortical circuitry and may provide a general mechanism for differentially routing information through the cortex.

Cortical signatures of sleep are altered following effective deep brain stimulation for depression.

Deep brain stimulation (DBS) of the subcallosal cingulate cortex (SCC) is an experimental therapy for treatment-resistant depression (TRD). Chronic SCC DBS leads to long-term changes in the electrophysiological dynamics measured from local field potential (LFP) during wakefulness, but it is unclear how it impacts sleep-related brain activity. This is a crucial gap in knowledge, given the link between depression and sleep disturbances, and an emerging interest in the interaction between DBS, sleep, and circadian rhythms. We therefore sought to characterize changes in electrophysiological markers of sleep associated with DBS treatment for depression. We analyzed key electrophysiological signatures of sleep-slow-wave activity (SWA, 0.5-4.5 Hz) and sleep spindles-in LFPs recorded from the SCC of 9 patients who responded to DBS for TRD. This allowed us to compare the electrophysiological changes before and after 24 weeks of therapeutically effective SCC DBS. SWA power was highly correlated between hemispheres, consistent with a global sleep state. Furthermore, SWA occurred earlier in the night after chronic DBS and had a more prominent peak. While we found no evidence for changes to slow-wave power or stability, we found an increase in the density of sleep spindles. Our results represent a first-of-its-kind report on long-term electrophysiological markers of sleep recorded from the SCC in patients with TRD, and provides evidence of earlier NREM sleep and increased sleep spindle activity following clinically effective DBS treatment. Future work is needed to establish the causal relationship between long-term DBS and the neural mechanisms underlying sleep.

Diurnal modulation of subthalamic beta oscillatory power in Parkinson's disease patients during deep brain stimulation.

Beta-band activity in the subthalamic local field potential (LFP) is correlated with Parkinson's disease (PD) symptom severity and is the therapeutic target of deep brain stimulation (DBS). While beta fluctuations in PD patients are well characterized on shorter timescales, it is not known how beta activity evolves around the diurnal cycle, outside a clinical setting. Here, we obtained chronic recordings (34 ± 13 days) of subthalamic beta power in PD patients implanted with the Percept DBS device during high-frequency DBS and analysed their diurnal properties as well as sensitivity to artifacts. Time of day explained 41 ± 9% of the variance in beta power (p < 0.001 in all patients), with increased beta during the day and reduced beta at night. Certain movements affected LFP quality, which may have contributed to diurnal patterns in some patients. Future DBS algorithms may benefit from taking such diurnal and artifactual fluctuations in beta power into account.

Diverse roles for the posteromedial thalamus in sensory-evoked cortical plasticity.

The posteromedial thalamus (POm) has extensive recurrent connectivity with the whisker-related primary somatosensory cortex (wS1) of rodents. However, its functional contribution to somatosensory processing in wS1 remains unclear. This article reviews several recent findings, which begin to elucidate the role of POm in sensory-evoked plasticity and discusses their implications for somatosensory processing.

Embryonic progenitor pools generate diversity in fine-scale excitatory cortical subnetworks.

The mammalian neocortex is characterized by a variety of neuronal cell types and precise arrangements of synaptic connections, but the processes that generate this diversity are poorly understood. Here we examine how a pool of embryonic progenitor cells consisting of apical intermediate progenitors (aIPs) contribute to diversity within the upper layers of mouse cortex. In utero labeling combined with single-cell RNA-sequencing reveals that aIPs can generate transcriptionally defined glutamatergic cell types, when compared to neighboring neurons born from other embryonic progenitor pools. Whilst sharing layer-associated morphological and functional properties, simultaneous patch clamp recordings and optogenetic studies reveal that aIP-derived neurons exhibit systematic biases in both their intralaminar monosynaptic connectivity and the post-synaptic partners that they target within deeper layers of cortex. Multiple cortical progenitor pools therefore represent an important factor in establishing diversity amongst local and long-range fine-scale glutamatergic connectivity, which generates subnetworks for routing excitatory synaptic information.

Stereosonic vision: Exploring visual-to-auditory sensory substitution mappings in an immersive virtual reality navigation paradigm.

Sighted people predominantly use vision to navigate spaces, and sight loss has negative consequences for independent navigation and mobility. The recent proliferation of devices that can extract 3D spatial information from visual scenes opens up the possibility of using such mobility-relevant information to assist blind and visually impaired people by presenting this information through modalities other than vision. In this work, we present two new methods for encoding visual scenes using spatial audio: simulated echolocation and distance-dependent hum volume modulation. We implemented both methods in a virtual reality (VR) environment and tested them using a 3D motion-tracking device. This allowed participants to physically walk through virtual mobility scenarios, generating data on real locomotion behaviour. Blindfolded sighted participants completed two tasks: maze navigation and obstacle avoidance. Results were measured against a visual baseline in which participants performed the same two tasks without blindfolds. Task completion time, speed and number of collisions were used as indicators of successful navigation, with additional metrics exploring detailed dynamics of performance. In both tasks, participants were able to navigate using only audio information after minimal instruction. While participants were 65% slower using audio compared to the visual baseline, they reduced their audio navigation time by an average 21% over just 6 trials. Hum volume modulation proved over 20% faster than simulated echolocation in both mobility scenarios, and participants also showed the greatest improvement with this sonification method. Nevertheless, we do speculate that simulated echolocation remains worth exploring as it provides more spatial detail and could therefore be more useful in more complex environments. The fact that participants were intuitively able to successfully navigate space with two new visual-to-audio mappings for conveying spatial information motivates the further exploration of these and other mappings with the goal of assisting blind and visually impaired individuals with independent mobility.

Sensory-Evoked Spiking Behavior Emerges via an Experience-Dependent Plasticity Mechanism.

The ability to generate action potentials (spikes) in response to synaptic input determines whether a neuron participates in information processing. How a developing neuron becomes an active participant in a circuit or whether this process is activity dependent is not known, especially as spike-dependent plasticity mechanisms would not be available to non-spiking neurons. Here we use the optic tectum of awake Xenopus laevis tadpoles to determine how a neuron becomes able to generate sensory-driven spikes in vivo. At the onset of vision, many tectal neurons do not exhibit visual spiking behavior, despite being intrinsically excitable and receiving visuotopically organized synaptic inputs. However, a brief period of visual stimulation can drive these neurons to start generating stimulus-driven spikes. This conversion relies upon a selective increase in glutamatergic input and requires depolarizing GABAergic transmission and NMDA receptor activation. This permissive form of experience-dependent plasticity enables a neuron to start contributing to circuit function.

Improving Mobility Performance in Low Vision With a Distance-Based Representation of the Visual Scene.

PURPOSE: Severe visual impairment can have a profound impact on personal independence through its effect on mobility. We investigated whether the mobility of people with vision low enough to be registered as blind could be improved by presenting the visual environment in a distance-based manner for easier detection of obstacles. METHODS: We accomplished this by developing a pair of "residual vision glasses" (RVGs) that use a head-mounted depth camera and displays to present information about the distance of obstacles to the wearer as brightness, such that obstacles closer to the wearer are represented more brightly. We assessed the impact of the RVGs on the mobility performance of visually impaired participants during the completion of a set of obstacle courses. Participant position was monitored continuously, which enabled us to capture the temporal dynamics of mobility performance. This allowed us to find correlates of obstacle detection and hesitations in walking behavior, in addition to the more commonly used measures of trial completion time and number of collisions. RESULTS: All participants were able to use the smart glasses to navigate the course, and mobility performance improved for those visually impaired participants with the worst prior mobility performance. However, walking speed was slower and hesitations increased with the altered visual representation. CONCLUSIONS: A depth-based representation of the visual environment may offer low vision patients improvements in independent mobility. It is important for further work to explore whether practice can overcome the reductions in speed and increased hesitation that were observed in our trial.

Visuospatial information in the retinotectal system of xenopus before correct image formation by the developing eye.

The retinotectal pathway of Xenopus laevis is a well-established experimental model for studying activity-dependent processes during visual system development. Such processes can be guided by stimulus-evoked activity patterns, which depend on the refractive characteristics of the eye. Previous work has shown that many animals are hyperopic at early developmental stages due to immature refractive properties. Whether this is also the case for Xenopus laevis is unknown. Here, we measure the focal length of the lens and the size of the eye of embryos at different stages and find that Xenopus laevis exhibits a similar shift from hyperopia to emmetropia. At early stages, immediately after innervation of the tectum by the optic nerve, Xenopus embryos are hyperopic. Soon afterwards the focal length of the lens decreases and the eye converges to a state of emmetropia. Despite being hyperopic we find that some visuospatial information is available to the young circuit. Calculations based on the optical properties of the eye show that even when the animals are hyperopic the blurred retinal image provides a crude spatial resolution. Furthermore, using whole-cell recordings in the optic tectum combined with visual stimulation through the intact eye, we show that tectal neurons in hyperopic embryos have spatially restricted glutamatergic receptive fields. Our data demonstrate that Xenopus laevis eyes undergo a process of developmental emmetropization, and suggest that despite an initial stage of suboptimal image formation there is potentially enough information to guide activity-dependent refinements of the retinotectal pathway from the onset of vision.

Simulating prosthetic vision: Optimizing the information content of a limited visual display.

Visual prostheses for the restoration of functional vision are currently under development. To guide prosthesis research and allow for an accurate prognosis of functional gain, simulating the experience of a retinal prosthesis in healthy individuals is desirable. Current simulation paradigms lack crucial aspects of the prosthetic experience such as realistic head- and eye-position-dependent image presentation. We developed a simulation paradigm that used a head-mounted camera and eye tracker to lock the simulation to the point of fixation. We evaluated visual acuity, object recognition and manipulation, and wayfinding under simulated prosthetic vision. We explored three ways of optimizing the information content of the prosthetic visual image: Full-Field representation (wide visual angle, low sampling frequency), Region of Interest (ROI; narrow visible angle, high sampling frequency), and Fisheye (high sampling frequency in the center, progressively lower resolution toward the edges). Full-Field representation facilitated visual search and navigation, whereas ROI improved visual acuity. The Fisheye representation, designed to incorporate the benefits of both Full-Field representation and ROI, performed similarly to ROI with subjects unable to capitalize on the peripheral data. The observation that different image representation conditions prove advantageous for different tasks should be taken into account in the process of designing and testing new visual prosthesis prototypes.

Differential effects of non-informative vision and visual interference on haptic spatial processing.

The primary purpose of this study was to examine the effects of non-informative vision and visual interference upon haptic spatial processing, which supposedly derives from an interaction between an allocentric and egocentric reference frame. To this end, a haptic parallelity task served as baseline to determine the participant-dependent biasing influence of the egocentric reference frame. As expected, large systematic participant-dependent deviations from veridicality were observed. In the second experiment we probed the effect of non-informative vision on the egocentric bias. Moreover, orienting mechanisms (gazing directions) were studied with respect to the presentation of haptic information in a specific hemispace. Non-informative vision proved to have a beneficial effect on haptic spatial processing. No effect of gazing direction or hemispace was observed. In the third experiment we investigated the effect of simultaneously presented interfering visual information on the haptic bias. Interfering visual information parametrically influenced haptic performance. The interplay of reference frames that subserves haptic spatial processing was found to be related to both the effects of non-informative vision and visual interference. These results suggest that spatial representations are influenced by direct cross-modal interactions; inter-participant differences in the haptic modality resulted in differential effects of the visual modality.