Differential Representation of Landmark and Self-Motion Information along the CA1 Radial Axis: Self-Motion Generated Place Fields Shift toward Landmarks during Septal Inactivation.

Spatial location in the environment can be defined in relation to specific landmarks or in relation to the global context, and is estimated from both the sensing of landmarks and the inner sense of cumulated locomotion referred to as path-integration. The respective contribution of landmark and path-integration to place-cell activity in the hippocampus is still unclear and complicated by the fact that the two mechanisms usually overlap. To bias spatial mechanisms toward landmark or path-integration, we use a treadmill equipped with a long belt on which male mice run sequentially through a zone enriched and a zone impoverished in visual-tactile cues. We show that inactivation of the medial septum (MS), which is known to disrupt the periodic activity of grid cells, impairs mice ability to anticipate the delivery of a reward in the cue-impoverished zone and transiently alter the spatial configuration of place fields in the cue-impoverished zone selectively: following MS inactivation, place fields in the cue-impoverished zone progressively shift backward and stabilize near the cues, resulting in the contraction of the spatial representation around cues; following MS recovery, the initial spatial representation is progressively restored. Furthermore, we found that place fields in the cue-rich and cue-impoverished zones are preferentially generated by cells from the deep and superficial sublayers of CA1, respectively. These findings demonstrate with mechanistic insights the contribution of MS to the spread of spatial representations in cue-impoverished zones, and indicate a segregation of landmark-based and path-integration-assisted spatial mechanisms into deep and superficial CA1, respectively.SIGNIFICANCE STATEMENT Cells encoding a cue-impoverished zone and the vicinity of landmarks responded differentially to septal inactivation and resided in distinct sublayers of CA1. These findings provide new insights on place field mechanisms: septal activity is critical for maintaining the spread of place fields in cue-impoverished areas, but not for the generation of place fields; Following MS inactivation, trial-by-trial network modifications by activity-dependent mechanisms are responsible for the gradual collapse of spatial representations. Furthermore, the findings suggest parallel coding streams for landmark and self-motion information. Superficial CA1 cells are better suited for encoding global position via the assist of path-integration, whereas deep CA1 cells can support spatial memory processes on an object-specific basis.

Compact single-shot four-wavelength quantitative phase microscopy with polarization- and frequency-division demultiplexing.

We present a novel single-shot four-wavelength quantitative phase microscopy (FW-QPM). Four lasers operating at different wavelengths are multiplexed with a pair of dichroic mirrors and a polarization beam splitter in a three-mirror quasi-common-path interferometer. After a single-shot interference pattern is obtained with a monochrome camera, four holograms of different wavelengths were demultiplexed from it in the frequency domain with polarization- and frequency-division multiplexing. Polarization-division demultiplexing scheme uses polarization dependent visibility changes in an interference pattern, and it plays a critical role in making only two interference patterns exist within a single quadrant in the frequency domain. We have used a single-mode optical fiber as a phase object sample and demonstrated that a measured single-shot interference pattern can be successfully demultiplexed into four different interferograms of different wavelengths with our proposed scheme.

Double-field-of-view, quasi-common-path interferometer using Fourier domain multiplexing.

We present a quasi-common-path interferometer with a double field of view (FOV). The laser beam of an imaging system is separated into three parts using three mirrors; the first and second beams are used to image two different areas of a sample, while the third beam functions as a reference beam. The reference beam is prepared by making clear area in a sample and projecting it on an image sensor. A double FOV is obtained by Fourier domain multiplexing, whereby two interferometric images corresponding to two different areas of a sample are modulated with two different spatial carrier frequencies. The feasibility of this technique is experimentally demonstrated by imaging two different areas of a test target with a single image sensor.

Large step-phase measurement by a reduced-phase triple-illumination interferometer.

We present a reduced-phase triple-illumination interferometer (RPTII) as a novel single-shot technique to increase the precision of dual-illumination optical phase unwrapping techniques. The technique employs two measurement ranges to record both low-precision unwrapped and high-precision wrapped phases. To unwrap the high-precision phase, a hierarchical optical phase unwrapping algorithm is used with the low-precision unwrapped phase. The feasibility of this technique is demonstrated by measuring a stepped object with a height 2100 times greater than the wavelength of the source. The phase is reconstructed without applying any numerical unwrapping algorithms, and its noise level is decreased by a factor of ten.

Reduced-phase dual-illumination interferometer for measuring large stepped objects.

We present a reduced-phase dual-illumination interferometer (RPDII) that measures the topography of a sample with large step height variation. We experimentally demonstrate the basic principle and the feasibility of this novel single-shot quantitative phase imaging. Two beams of this interferometer illuminate a sample at different incident angles, and two phases of the different incident angles and their phase difference are simultaneously recorded using three spatial frequencies. The relative phase difference between two beams of an RPDII can be controlled by adjusting the angle such that the maximum phase difference is smaller than 2π, and thus there is no phase wrapping ambiguity in the reconstructed phase. One 4f optical system with a transmission grating is used to illuminate the sample with two collimated beams incident at different angles. The feasibility of this technique is demonstrated by measuring the thicknesses of two stepped metal layers with heights of 150 and 660 µm. Although the change in stepped height is more than 1000 times the wavelength of the laser used in our interferometer, the thicknesses of these two metal layers are successfully obtained without the use of an unwrapping algorithm.

Subcircuits of Deep and Superficial CA1 Place Cells Support Efficient Spatial Coding across Heterogeneous Environments.

The hippocampus is thought to guide navigation by forming a cognitive map of space. Different environments differ in geometry and the availability of cues that can be used for navigation. Although several spatial coding mechanisms are known to coexist in the hippocampus, how they are influenced by various environmental features is not well understood. To address this issue, we examined the spatial coding characteristics of hippocampal neurons in mice and rats navigating in different environments. We found that CA1 place cells located in the superficial sublayer were more active in cue-poor environments and preferentially used a firing rate code driven by intra-hippocampal inputs. In contrast, place cells located in the deep sublayer were more active in cue-rich environments and used a phase code driven by entorhinal inputs. Switching between these two spatial coding modes was supported by the interaction between excitatory gamma inputs and local inhibition.

Smart filtering of phase residues in noisy wrapped holograms.

Phase unwrapping is one of the major challenges in multiple branches of science that extract three-dimensional information of objects from wrapped signals. In several applications, it is important to extract the unwrapped information with minimal signal resolution degradation. However, most of the denoising techniques for unwrapping are designed to operate on the entire phase map to remove a limited number of phase residues, and therefore they significantly degrade critical information contained in the image. In this paper, we present a novel, smart, and automatic filtering technique for locally minimizing the number of phase residues in noisy wrapped holograms, based on the phasor average filtering (PAF) of patches around each residue point. Both patch sizes and PAF filters are increased in an iterative algorithm to minimize the number of residues and locally restrict the artifacts caused by filtering to the pixels around the residue pixels. Then, the improved wrapped phase can be unwrapped using a simple phase unwrapping technique. The feasibility of our method is confirmed by filtering, unwrapping, and enhancing the quality of a noisy hologram of neurons; the intensity distribution of the spatial frequencies demonstrates a 40-fold improvement, with respect to previous techniques, in preserving the higher frequencies.

Dentate granule and mossy cells exhibit distinct spatiotemporal responses to local change in a one-dimensional landscape of visual-tactile cues.

The dentate gyrus (DG) is critical for detecting changes in environments; however, how granule cells (GCs) and mossy cells (MCs), the two excitatory cell types of the DG, respond to small changes in the object layout is unclear. Here, we recorded GCs and MCs, identified by spike feature and optogenetic tagging, as mice ran on a treadmill belt enriched with visual-tactile cues. We observed that fixing a new cue on the belt induced a reconfiguration of GC and MC spatial representations via the emergence, extinction and rate alteration of firing fields. For both GCs and MCs, the response was maximal near the cue and spread over the entire belt. However, compared to the GC response, the MC response was stronger and more immediate, peaked at a slightly earlier belt position, and exhibited a transient component reminiscent of neuromodulatory activity. A competitive neural network model reproduced the GC response contingent on both the introduction of new object-vector inputs and the reconfiguration of MC activity, the former being critical for spreading the GC response in locations distant from the cue. These findings suggest that GCs operate as a competitive network and that MCs precede GCs in detecting changes and help expand the range of GC pattern separation.

Author Correction: Dentate granule and mossy cells exhibit distinct spatiotemporal responses to local change in a one-dimensional landscape of visual-tactile cues.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Micro-drive and headgear for chronic implant and recovery of optoelectronic probes.

Silicon probes are multisite electrodes used for the electrophysiological recording of large neuronal ensembles. Optoelectronic probes (OEPs) are recent upgrades that allow, in parallel, the delivery of local optical stimuli. The procedures to use these delicate electrodes for chronic experiments in mice are still underdeveloped and typically assume one-time uses. Here, we developed a micro-drive, a support for OEPs optical fibers, and a hat enclosure, which fabrications consist in fitting and fastening together plastic parts made with 3D printers. Excluding two parts, all components and electrodes are relatively simple to recover after the experiments, via the loosening of screws. To prevent the plugging of OEPs laser sources from altering the stability of recordings, the OEPs fibers can be transiently anchored to the hat via the tightening of screws. We test the stability of recordings in the mouse hippocampus under three different conditions: acute head-fixed, chronic head-fixed, and chronic freely moving. Drift in spike waveforms is significantly smaller in chronic compared to acute conditions, with the plugging/unplugging of head-stage and fiber connectors not affecting much the recording stability. Overall, these tools generate stable recordings of place cell in chronic conditions, and make the recovery and reuse of electrode packages relatively simple.

Implantation of Chronic Silicon Probes and Recording of Hippocampal Place Cells in an Enriched Treadmill Apparatus.

An important requisite for understanding brain function is the identification of behavior and cell activity correlates. Silicon probes are advanced electrodes for large-scale electrophysiological recording of neuronal activity, but the procedures for their chronic implantation are still underdeveloped. The activity of hippocampal place cells is known to correlate with an animal's position in the environment, but the underlying mechanisms are still unclear. To investigate place cells, here we describe a set of techniques which range from the fabrication of devices for chronic silicon probe implants to the monitoring of place field activity in a cue-enriched treadmill apparatus. A micro-drive and a hat are built by fitting and fastening together 3D-printed plastic parts. A silicon probe is mounted on the micro-drive, cleaned, and coated with dye. A first surgery is performed to fix the hat on the skull of a mouse. Small landmarks are fabricated and attached to the belt of a treadmill. The mouse is trained to run head-fixed on the treadmill. A second surgery is performed to implant the silicon probe in the hippocampus, following which broadband electrophysiological signals are recorded. Finally, the silicon probe is recovered and cleaned for reuse. The analysis of place cell activity in the treadmill reveals a diversity of place field mechanisms, outlining the benefit of the approach.