Biology subjects

Knierim, J. J.

Publications and source records attributed to Knierim, J. J..

16 recordsLinked to original sources

bioRxiv2026

Hippocampal theta frequency as a readout of path-integration recalibration

Understanding how the brain represents hidden variables is a fundamental challenge. In navigation, the internal path-integration gain is often masked by external landmarks that override the path integrator. Path integration can recalibrate its gain when allothetic and idiothetic cues conflict, but the real-time dynamics of this process are hidden to direct observation. Here, we demonstrate that theta frequency provides an error signal between the observable hippocampal gain and the internal path-integration gain. Theta frequency decreased as conflict between landmark-driven hippocampal gain and path-integration gain increased and recovered as the path-integration gain recalibrated to the new gain. A continuous attractor model replicated these dynamics, suggesting that the theta-frequency drop is driven by the misalignment of allothetic and idiothetic inputs, reducing the excitatory drive to the network. Thus, theta frequency provides a real-time readout of internal gain-error signals, offering a novel methodology to estimate hidden cognitive variables through observable physiological oscillations.

neuroscience↗

bioRxiv2025

Visual landmark coding and dynamic coupling with path integration circuits in area 29e of the rodent parahippocampal cortex

External landmarks anchor internal spatial representations. The neural mechanisms underlying this process and the sources of landmark signals remain unknown. We recorded neurons across five parahippocampal regions while rats navigated in a virtual reality apparatus, inducing conflict between self-motion and landmark cues. Area 29e, a parahippocampal field putatively homologous to primate area prostriata, maintained firing coupled to landmarks even when other regions decoupled from the landmarks. This decoupling was preceded by a decline of gamma-band influence from 29e to MEC and a concomitant decline of theta-modulated feedback from MEC to 29e. Area 29e also displayed weak theta modulation, strong gamma rhythmicity, strong egocentric head-direction tuning, and enhanced landmark contrast sensitivity. These findings provide strong evidence that 29e serves as a specialized visuospatial hub that provides landmark signals for anchoring parahippocampal spatial representations to the external world.

neuroscience↗

bioRxiv2025

Synchronized path-integration recalibration but distinct landmark-control dynamics in head direction and CA1 place cells

Accurate spatial navigation relies on path integration, a process of tracking ones location by integrating self-motion cues. Path integration uses a gain factor relating self-motion signals to displacement on the cognitive map. This gain is plastic, recalibrating rapidly to match perceived displacements relative to external cues. To elucidate the mechanism of recalibration, we simultaneously recorded from place cells, which instantiate the cognitive map, and head direction (HD) cells, thought to orient the map. Persistent conflict between self-motion and visual feedback induced functionally identical recalibration of path-integration gain in the two neural populations during forward locomotion; however, during locomotor immobility accompanied by head-scanning, HD cells did not exhibit recalibration. Moreover, the two populations manifested differential field-shifting dynamics relative to landmarks during recalibration. These results uncover a tightly coordinated yet behavior-dependent recalibration process across the navigation circuit that achieves a robust yet flexible coupling of the internal sense of position and direction.

neuroscience↗

bioRxiv2024

Continuous Bump Attractor Networks Require Explicit Error Coding for Gain Recalibration

Representations of continuous variables are crucial to create internal models of the external world. A prevailing model of how the brain maintains these representations is given by continuous bump attractor networks (CBANs) in a broad range of brain functions across different areas, such as spatial navigation in hippocampal/entorhinal circuits and working memory in prefrontal cortex. Through recurrent connections, a CBAN maintains a persistent activity bump, whose peak location can vary along a neural space, corresponding to different values of a continuous variable. To track the value of a continuous variable changing over time, a CBAN updates the location of its activity bump based on inputs that encode the changes in the continuous variable (e.g., movement velocity in the case of spatial navigation)--a process akin to mathematical integration. This integration process is not perfect and accumulates error over time. For error correction, CBANs can use additional inputs providing ground-truth information about the continuous variables correct value (e.g., visual landmarks for spatial navigation). These inputs enable the network dynamics to automatically correct any representation error. Recent experimental work on hippocampal place cells has shown that, beyond correcting errors, ground-truth inputs also fine-tune the gain of the integration process, a crucial factor that links the change in the continuous variable to the updating of the activity bumps location. However, existing CBAN models lack this plasticity, offering no insights into the neural mechanisms and representations involved in the recalibration of the integration gain. In this paper, we explore this gap by using a ring attractor network, a specific type of CBAN, to model the experimental conditions that demonstrated gain recalibration in hippocampal place cells. Our analysis reveals the necessary conditions for neural mechanisms behind gain recalibration within a CBAN. Unlike error correction, which occurs through network dynamics based on ground-truth inputs, gain recalibration requires an additional neural signal that explicitly encodes the error in the networks representation via a rate code. Finally, we propose a modified ring attractor network as an example CBAN model that verifies our theoretical findings. Combining an error-rate code with Hebbian synaptic plasticity, this model achieves recalibration of integration gain in a CBAN, ensuring accurate representation for continuous variables.

neuroscience↗

bioRxiv2024

Multiplexing of temporal and spatial information in the lateral entorhinal cortex

Episodic memory involves the processing of spatial and temporal aspects of personal experiences. The lateral entorhinal cortex (LEC) plays an essential role in subserving memory. However, the specific mechanism by which LEC integrates spatial and temporal information remains elusive. Here, we recorded LEC neurons while rats performed foraging and shuttling behaviors on one-dimensional, linear or circular tracks. Unlike open-field foraging tasks, many LEC cells displayed spatial firing fields in these tasks and demonstrated selectivity for traveling directions. Furthermore, some LEC neurons displayed changes in the firing rates of their spatial rate maps during a session, a phenomenon referred to as rate remapping. Importantly, this temporal modulation was consistent across sessions, even when the spatial environment was altered. Notably, the strength of temporal modulation was found to be greater in LEC compared to other brain regions, such as the medial entorhinal cortex (MEC), CA1, and CA3. Thus, the spatial rate mapping observed in LEC neurons may serve as a coding mechanism for temporal context, allowing for flexible multiplexing of spatial and temporal information.

neuroscience↗

bioRxiv2023

Conjunctive vector coding and place coding in hippocampus share a common directional signal

Vector coding is becoming increasingly understood as a major mechanism by which neural systems represent an animals location in both a global reference frame and a local, item-based reference frame. Landmark vector cells (LVCs) in the hippocampus complement classic place cells by encoding the vector relationship (angle and distance) between the individual and specific landmarks in the environment. How these properties of hippocampal principal cells interact is not known. We simultaneously recorded the activities of place cells and LVCs via in vivo calcium imaging of the CA1 region of freely moving rats during classic, cue-card rotation studies. The firing fields of place cells rotated relative to the center of the platform to follow the cue card rotation, whereas the firing fields of simultaneously recorded LVCs rotated by the same amount as the place cells, but the axis of rotation was the nearby local landmarks, not the environmental center. We identified a novel type of place cell that exhibited conjunctive coding of the classic place field properties and LVC properties. These results demonstrate the capacity of CA1 neurons to encode both world-centered spatial information and animals location relative to the local landmarks, with a common directional input presumably provided by the head direction cell system.

neuroscience↗

bioRxiv2022

Global remapping in granule cells and mossy cells of the mouse dentate gyrus

Hippocampal place cells exhibit spatially modulated firing, or place fields, which can remap to encode changes in the environment or other variables. Unique among hippocampal subregions, the dentate gyrus (DG) has two excitatory populations of place cells, granule cells and mossy cells, which are among the least and most active spatially modulated cells in the hippocampus, respectively. Previous studies of remapping in the DG have drawn different conclusions about whether granule cells exhibit global remapping and contribute to the encoding of context specificity. By recording granule cells and mossy cells as mice foraged in different environments, we found that by most measures, both granule cells and mossy cells remapped robustly but through different mechanisms that are consistent with firing properties of each cell type. Our results resolve the ambiguity surrounding remapping in the DG and suggest that most spatially modulated granule cells contribute to orthogonal representations of distinct spatial contexts.

neuroscience↗

bioRxiv2022

Closed-loop control and recalibration of place cells by optic flow

Understanding the interplay between sensory input, endogenous neural dynamics, and behavioral output is key toward understanding the principles of neural computation. Hippocampal place cells are an ideal system to investigate this closed-loop interaction, as they are influenced by both self-motion (idiothetic) signals and by external sensory landmarks as an animal navigates its environment1-9. To continuously update a position signal on an internal "cognitive map", the hippocampal system integrates self-motion signals over time10,11. In the absence of stable, external landmarks, however, these spatial correlates of neuronal activity can quickly accumulate error and cause the internal representation of position or direction to drift relative to the external environment1,5. We have previously demonstrated that, in addition to their known roles in preventing and/or correcting path-integration error, external landmarks can be used as a putative teaching signal to recalibrate the gain of the path integration system6. However, it remains unclear whether idiothetic cues, such as optic flow, exert sufficient influence on the cognitive map to enable recalibration of path integration, or if instead an unambiguous allocentric frame of reference, anchored by polarizing landmark information, is essential for path integration recalibration. Here, we use principles of control theory12,13 to demonstrate systematic control of place fields by pure optic flow information in freely moving animals by using a neurally closed-loop virtual reality system that adjusts optic flow speed as a function of real-time decoding of the hippocampal spatial map. Using this "cognitive clamp", we show that we can not only bring the updating of the map under control of the optic flow cues but we can also elicit recalibration of path integration. This finding demonstrates that the brain continuously rebalances the influence of conflicting idiothetic cues to fine-tune the neural dynamics of path integration, and that this recalibration process does not require a top-down, unambiguous position signal from landmarks.

neuroscience↗

bioRxiv2022

Leveraging place field repetition to understand positional versus nonpositional inputs to hippocampal field CA1

The hippocampus is believed to encode episodic memory by binding information about the content of experience within a spatiotemporal framework encoding the location and temporal context of that experience. Previous work implies a distinction between positional inputs to the hippocampus that provide information about an animals location and nonpositional inputs which provide information about the content of experience, both sensory and navigational. Here we leverage the phenomenon of "place field repetition" to better understand the functional dissociation between positional and nonpositional inputs to CA1. Rats navigated freely on a novel maze consisting of linear segments arranged in a rectilinear, city-block configuration, which combined elements of open-field foraging and linear-track tasks. Unlike typical results in open-field foraging, place fields were directionally tuned on the maze, even though the animals behavior was not constrained to 1-D trajectories. Repeating fields from the same cell tended to have the same directional preference when the fields were aligned along a linear corridor of the maze, but they showed uncorrelated directional preferences when they were unaligned across different corridors. Lastly, individual fields displayed complex time dynamics which resulted in the population activity changing gradually over the course of minutes. These temporal dynamics were evident across repeating fields of the same cell. These results demonstrate that the positional inputs that drive a cell to fire in similar locations across the maze can be behaviorally and temporally dissociated from the nonpositional inputs that alter the firing rates of the cell within its place fields, thereby increasing the flexibility of the system to encode episodic variables within a spatiotemporal framework provided by place cells.

neuroscience↗

bioRxiv2021

Proximal CA3 is the primary locus of age-related pattern separation deficits in rats

Age-related deficits in pattern separation have been postulated to bias the output of hippocampal memory processing toward pattern completion, which can cause deficits in accurate memory retrieval. While the CA3 region of the hippocampus is often conceptualized as a homogeneous network involved in pattern completion, growing evidence demonstrates a functional gradient in CA3 along the transverse axis, as pattern-separated outputs (dominant in the more proximal CA3) transition to pattern-completed outputs (dominant in the more distal CA3). We examined the neural representations along the CA3 transverse axis in young (Y), aged memory-unimpaired (AU), and aged memory-impaired (AI) rats when different changes were made to the environment. Functional heterogeneity in CA3 was observed in Y and AU rats when the environmental similarity was high (altered cues or altered environment shapes in the same room), with more orthogonalized representations in proximal CA3 than in distal CA3. In contrast, AI rats showed reduced orthogonalization in proximal CA3 but showed normal (i.e., generalized) representations in distal CA3, with little evidence of a functional gradient. Under experimental conditions when the environmental similarity was low (different rooms), representations in proximal and distal CA3 remapped in all rats, showing that CA3 of AI rats is able to encode distinctive representations for inputs with greater dissimilarity. These experiments support the hypotheses that the aged-related bias towards hippocampal pattern completion is due to the loss in AI rats of the normal transition from pattern separation to pattern completion along the CA3 transverse axis.

animal behavior and cognition↗

bioRxiv2021

Wide-Angle, Monocular Head Tracking using Passive Markers

Camera images can encode large amounts of visual information of an animal and its environment, enabling high fidelity 3D reconstruction of the animal and its environment using computer vision methods. Most systems, both markerless (e.g. deep learning based) and marker-based, require multiple cameras to track features across multiple points of view to enable such 3D reconstruction. However, such systems can be expensive and are challenging to set up in small animal research apparatuses. We present an open-source, marker-based system for tracking the head of a rodent for behavioral research that requires only a single camera with a potentially wide field of view. The system features a lightweight visual target and computer vision algorithms that together enable high-accuracy tracking of the six-degree-of-freedom position and orientation of the animals head. The system, which only requires a single camera positioned above the behavioral arena, robustly reconstructs the pose over a wide range of head angles (360{whitebullet} in yaw, and approximately {+/-}120{whitebullet} in roll and pitch). Experiments with live animals demonstrate that the system can reliably identify rat head position and orientation. Evaluations using a commercial optical tracker device show that the system achieves accuracy that rivals commercial multi-camera systems. Our solution significantly improves upon existing monocular marker-based tracking methods, both in accuracy and in allowable range of motion. The proposed system enables the study of complex behaviors by providing robust, fine-scale measurements of rodent head motions in a wide range of orientations.

neuroscience↗

bioRxiv2021

Flexible encoding of objects and space in single cells of the dentate gyrus

The hippocampus is involved in the formation of memories that require associations among stimuli to construct representations of space and the items and events within that space. Neurons in the dentate gyrus (DG), an initial input region of the hippocampus, have robust spatial tuning, but it is unclear how nonspatial information may be integrated with spatially modulated firing at this stage. We recorded from the DG of 21 adult mice as they foraged for food in an environment that contained discrete objects. By classifying recorded DG cells into putative granule cells and mossy cells, we examined how the addition or displacement of objects affected the spatial firing of these DG cell types. We found DG cells with multiple firing fields at a fixed distance and direction from objects (landmark vector cells) as well as cells that exhibited localized changes in spatial firing when objects in the environment were manipulated. When mice were exposed to a second environment with the same objects, DG spatial maps were completely reorganized, suggesting standard global remapping, and a largely different subset of cells responded to object manipulations. Together, these data reveal the capacity of DG cells to detect small changes in the environment, while preserving a stable spatial representation of the overall context.

neuroscience↗

bioRxiv2020

Heterogeneity of age-related neural hyperactivity along the CA3 transverse axis

Age-related memory deficits are correlated with neural hyperactivity in the CA1 and CA3 regions of the hippocampus. Abnormal CA3 hyperactivity in aged rats has been proposed to contribute to an imbalance between the normal tradeoff between pattern separation and pattern completion, resulting in overly rigid representations. Recent evidence of functional heterogeneity along the CA3 transverse axis suggests that proximal CA3 supports pattern separation while distal CA3 supports pattern completion. It is not known whether age-related CA3 hyperactivity is uniformly represented along the CA3 transverse axis. We examined the firing rates of CA3 neurons from male young and aged Long-Evans rats along the CA3 transverse axis. Consistent with prior studies, young CA3 cells showed an increasing gradient in mean firing rate from proximal to distal CA3. However, aged CA3 cells showed an opposite trend, with a decreasing gradient from proximal to distal CA3. Thus, CA3 cells in aged rats were hyperactive in proximal CA3, but possibly hypoactive in distal CA3, compared to young rats. We suggest that, in combination with altered inputs from the entorhinal cortex and dentate gyrus, the proximal CA3 region of aged rats may switch from its normal function that reflects the pattern separation output of the DG and instead performs a computation that reflects an abnormal bias toward pattern completion. In parallel, distal CA3 of aged rats may create weaker attractor basins that promote bistable representations under certain conditions.

neuroscience↗

bioRxiv2020

Decreased investigatory head scanning during exploration in learning-impaired, aged rats

"Head scanning" is an investigatory behavior that has been linked to spatial exploration and the one-trial formation or strengthening of place cells in the hippocampus. Previous studies have demonstrated that a subset of aged rats with normal spatial learning performance show head scanning rates during a novel, local-global cue-mismatch manipulation that are similar to those of young rats. However, these aged rats demonstrated different patterns of expression of neural activity markers in brain regions associated with spatial learning, perhaps suggesting neural mechanisms that compensate for age-related brain changes. These prior studies did not investigate the head scanning properties of aged rats that had spatial learning impairments. The present study analyzed head scanning behavior in young, aged-unimpaired, and aged-impaired Long Evans rats. Aged-impaired rats performed the head scan behavior at a lower rate than the young rats. These results suggest that decreased attention to spatial landmarks may be a contributing factor to the spatial learning deficits shown by the aged-impaired rats.

animal behavior and cognition↗

bioRxiv2019

Hippocampal place cells encode local surface texture boundaries

The cognitive map is often assumed to be a Euclidean map that isometrically represents the real world (i.e. the Euclidean distance between any two locations in the physical world should be preserved on the cognitive map). However, accumulating evidence suggests that environmental boundaries can distort the mental representations of a physical space. For example, the distance between two locations can be remembered as longer than the true physical distance if the locations are separated by a boundary. While this overestimation is observed under different experimental conditions, even when the boundary is formed by flat surface cues, its physiological basis is not well understood. We examined the neural representation of flat surface cue boundaries, and of the space segregated by these boundaries, by recording place cell activity from dorsal CA1 and CA3 while rats foraged on a circular track or square platform with inhomogeneous surface textures. About 40% of the place field edges concentrated near the surface cue boundaries on the circular track (significantly above the chance level 33%). Similarly, the place field edges were more prevalent near the boundaries on the platforms than expected by chance. In both 1-dimensional and 2-dimensional environments, the population vectors of place cell activity changed more abruptly with distance between locations that crossed cue boundaries than between locations within a bounded region. These results show that the locations of surface boundaries were evident as enhanced decorrelations of the neural representations of locations to either side of the boundaries. This enhancement might underlie the cognitive phenomenon of overestimation of distances across boundaries.

neuroscience↗

bioRxiv2018

Recalibration of path integration in hippocampal place cells

Hippocampal place cells are spatially tuned neurons that serve as elements of a \"cognitive map\" in the mammalian brain1. To detect the animals location, place cells are thought to rely upon two interacting mechanisms: sensing the animals position relative to familiar landmarks2,3 and measuring the distance and direction that the animal has travelled from previously occupied locations4-7. The latter mechanism, known as path integration, requires a finely tuned gain factor that relates the animals self-movement to the updating of position on the internal cognitive map, with external landmarks necessary to correct positional error that eventually accumulates8,9. Path-integration-based models of hippocampal place cells and entorhinal grid cells treat the path integration gain as a constant9-14, but behavioral evidence in humans suggests that the gain is modifiable15. Here we show physiological evidence from hippocampal place cells that the path integration gain is indeed a highly plastic variable that can be altered by persistent conflict between self-motion cues and feedback from external landmarks. In a novel, augmented reality system, visual landmarks were moved in proportion to the animals movement on a circular track, creating continuous conflict with path integration. Sustained exposure to this cue conflict resulted in predictable and prolonged recalibration of the path integration gain, as estimated from the place cells after the landmarks were extinguished. We propose that this rapid plasticity keeps the positional update in register with the animals movement in the external world over behavioral timescales (mean 50 laps over 35 minutes). These results also demonstrate that visual landmarks not only provide a signal to correct cumulative error in the path integration system, as has been previously shown4,8,16-19, but also rapidly fine-tune the integration computation itself.

neuroscience↗