Biology subjects

van der Meer, M. A.

Publications and source records attributed to van der Meer, M. A..

7 recordsLinked to original sources

bioRxiv2026

A canonical input to the head direction compass carries predominantly eye movement signals

The mammalian head direction (HD) system is thought to update its internal compass using angular head velocity (AHV) signals relayed from the brainstem. We tested this canonical interpretation by recording from the nucleus prepositus hypoglossi (NPH), a proposed AHV relay known to be important for accurate HD tracking, while simultaneously measuring eye and head movements in mice. Neurons classified as AHV-tuned instead predominantly encoded eye movements: most showed saccade-related bursts or pauses, and apparent AHV tuning was largely explained by eye rather than head motion. Optotagging showed that even NPH neurons projecting directly to the HD circuit predominantly encoded eye movements. Empirically constrained population models reconstructed eye position and gaze direction, but head-direction readouts failed when eye and head motion were dissociated. These findings overturn the canonical view of NPH as a dedicated AHV relay, revealing eye movements as a major, previously unmeasured component of the signals entering the mammalian HD circuit and thereby changing the computational problem that the HD system must solve to maintain a stable representation of heading.

neuroscience↗

bioRxiv2026

Hippocampal theta distinguishes between memory-guided and exploratory saccades in humans

Memory shapes how we explore the visual world, but the neural mechanisms linking mnemonic processes to eye movements during naturalistic viewing are not well understood. Theta-band oscillatory activity in the hippocampus is time-locked with eye movements in primates, suggesting a putative mechanism for coordinating mnemonic processing and oculomotor behaviour. Yet, it remains unknown whether this coupling generalises to episodic memory-guided viewing in humans, whether slow (3-6 Hz) and fast (6-10 Hz) theta bands play dissociable functions, and whether this coupling is sensitive to the direction of upcoming eye movements. Here, we used intracranial EEG and eye-tracking data from 11 neurosurgical patients of either sex (Keles et al., 2024) to address these questions. Using fixation-locked analyses, we found that hippocampal theta dynamics differentiate memory-guided from memory-independent fixations of episodically encoded naturalistic scenes (i.e., movies) through power and coherence mechanisms that are both temporally and spectrally dissociable. First, immediately after fixations ([~]0 to 250 ms), slow-theta power was more strongly suppressed during memory-guided trials (i.e., true positive, TP) than correct memory-independent trials (i.e., true negative, TN). Second, in the period around fixations (-80 to 60 ms), theta phase coherence increased independent of power during TP vs TN trials. This increase in coherence was most pronounced for contraversive relative to ipsiversive fixations, consistent with direction-sensitive hippocampal-oculomotor coordination during memory-guided viewing. Together, these findings suggest that hippocampal theta plays dissociable, time-locked roles in memory-guided fixations during naturalistic visual retrieval, supporting an ecologically relevant role for the hippocampus in coordinating memory and active visual behaviour. Significance statementMemory influences how we sample the visual environment, but the brain signals that link memory systems to eye movements are poorly understood. Using intracranial recordings from the human hippocampus during visual exploration of naturalistically encoded scenes, we demonstrate that theta-band activity differentiates memory-guided from memory-independent fixations in two ways: increased theta synchrony around fixation onset and reduced theta power modulations after fixation onset. These results reveal novel insights into how hippocampal theta helps coordinate memory-guided visual exploration.

neuroscience↗

bioRxiv2026

State-dependent geometric transformations in the mouse hippocampus support fear generalization without loss of discriminability

Learning from aversive experiences often generalizes beyond the context in which they occurred. In rodents, a strong aversive event can induce retrospective memory linking (RLI), whereby fear generalizes to a previously neutral context encountered days earlier. Although prior work has shown that RLI is associated with increased co-activity of hippocampal CA1 neurons across neutral and aversive contexts, it remains unclear how broader representational changes support generalization without affecting the ability to discriminate between contexts. Here, we reanalyzed calcium imaging data from dorsal CA1 during RLI to examine how hippocampal representational geometry changes during fear generalization. Using robust, non-parametric measures of population similarity, we show that in mice exhibiting RLI, the representation of the neutral context not only changes over time but becomes more similar to the aversive context during recall. Beyond this similarity increase, we provide evidence for a higher-dimensional geometric transformation consistent with a shared "fear" operation that can be applied across contexts while preserving their identity. Crucially, these two representational signatures dissociate by behavioral state: similarity to the aversive context emerges during freezing, whereas a shared transformation is expressed during active exploration. Together, these findings demonstrate that hippocampal representations support retrospective fear generalization through state-dependent geometric transformations, highlighting representational geometry as a key computational mechanism to resolve the apparent tension between generalization and discriminability.

neuroscience↗

bioRxiv2025

Ventral Striatal Dopamine Increases following Hippocampal Sharp-Wave Ripples

The reactivation of task-related hippocampal activity during sharp-wave ripples (SWRs), often expressed as sequential "replay," is thought to contribute to behavior through both online and offline processes. Theories of replay-based learning and decision-making posit the need for replay events to be followed by an evaluative signal. Dopamine (DA) is a prime candidate for providing such a signal, particularly in the ventral striatum, where it reflects reward- and other prediction-error signals. Hippocampal activity influences mesolimbic dopamine signaling and neural activity in the ventral striatum, but it is unknown whether SWRs are coupled to ventral striatal DA release. To address this, we simultaneously recorded dorsal CA1 local field potentials to detect SWRs and measured ventral striatal DA concentration using fiber photometry in freely moving mice. We found a significant increase in DA following SWRs. This coupling was more prominent during offline rest than during periods of immobility during behavior, and was stronger following longer and higher-power SWRs. These results reveal coupling between hippocampal SWRs and striatal dopamine, providing a potential candidate mechanism through which internally generated hippocampal activity could engage evaluative signals during offline memory processing.

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bioRxiv2024

Optogenetic mapping of rhythmic phase-dependentexcitability in the mouse striatum

The striatum is thought to switch flexibly between multiple converging inputs to support adaptive behavior. The "communication through coherence" (CTC) hypothesis is a potential mechanism to implement such a flexible switching. For CTC to work in the striatum, striatal excitability must show rhythmic fluctuations, such as those related to the phase of the striatal local field potential (LFP). To test this fundamental requirement, we delivered a constant input stimulus to ChR2-expressing striatal fast-spiking PV+ interneurons (FSIs) in head-fixed awake mice (PV-Cre:Ai-32, n = 18, 9 female), and determined whether the response to this stimulus varied with LFP phase. We found that approximately one-third (41.2%) of FSIs exhibited significant phase-dependent excitability in at least one LFP frequency band. Phase-dependent excitability was most prominent in the delta (2-5 Hz) frequency band, both in terms of prevalence (23.5% of FSIs sampled) and magnitude (phase modulation strength: 22% of average response). The most excitable phase tended to align with endogenous phase-locking, again most clearly in the delta band. These results bolster the functional relevance of the striatal field potential and spike-field relationships, and provide proof-of-principle support for the possibility of CTC in the striatum. Significance StatementThe striatum is thought to switch dynamically between multiple converging inputs. A leading idea for how this is accomplished is through communication through coherence (CTC). A fundamental, but previously untested, requirement for CTC to work is that striatum must show changes in excitability that depend on local field potential phase. We find that about one-third of striatal neurons show phase-dependent excitability, providing proof of principle for CTC-like switching in striatum.

neuroscience↗

bioRxiv2020

Between-subject prediction reveals a shared representational geometry in the rodent hippocampus

The rodent hippocampus constructs statistically independent representations across environments ("global remapping") and assigns individual neuron firing fields to locations within an environment in an apparently random fashion, processes thought to contribute to the role of the hippocampus in episodic memory. This random mapping implies that it should be challenging to predict hippocampal encoding of a given experience in one subject based on the encoding of that same experience in another subject. Contrary to this prediction, we find that by constructing a common representational space across rats in which neural activity is aligned using geometric operations (rotation, reflection, and translation; "hyperalignment"), we can predict data of "right" trials (R) on a T-maze in a target rat based on 1) the "left" trials (L) of the target rat, and 2) the relationship between L and R trials from a different source rat. These cross-subject predictions relied on ensemble activity patterns including both firing rate and field location, and outperformed a number of control mappings, such as those based on permuted data that broke the relationship between L and R activity for individual neurons, and those based solely on within-subject prediction. This work constitutes proof-of-principle for successful cross-subject prediction of ensemble activity patterns in the hippocampus, and provides new insights in understanding how different experiences are structured, enabling further work identifying what aspects of experience encoding are shared vs. unique to an individual.

neuroscience↗

bioRxiv2017

Gamma Oscillations In The Rat Ventral Striatum Originate In The Piriform Cortex

Local field potentials (LFP) recorded from the human and rodent ventral striatum (vStr) exhibit prominent, behaviorally relevant gamma-band oscillations. These oscillations are related to local spiking activity and transiently synchronize with anatomically related areas, suggesting a possible role in organizing vStr activity. However, the origin of vStr gamma is unknown. We recorded vStr gamma oscillations across a 1.4mm2 grid spanned by 64 recording electrodes as rats rested and foraged for rewards, revealing a highly consistent power gradient originating in the adjacent piriform cortex. Phase differences across the vStr were consistently small (<10{degrees}) and current source density analysis further confirmed the absence of local sink-source pairs in the vStr. Reversible occlusions of the ipsilateral (but not contralateral) nostril, known to abolish gamma oscillations in the piriform cortex, strongly reduced vStr gamma power and the occurrence of transient gamma-band events. These results imply that local circuitry is not a major contributor to gamma oscillations in the vStr LFP, and that piriform cortex is an important driver of gamma-band oscillations in the vStr and associated limbic areas.\n\nSignificance StatementThe ventral striatum is an area of anatomical convergence in circuits underlying motivated behavior, but it remains unclear how its inputs from different sources interact. One of the major proposals of how neural circuits may dynamically switch between convergent inputs is through temporal organization reflected in local field potential (LFP) oscillations. Our results show that in the rat, the mechanisms controlling vStr gamma oscillations are primarily located in the in the adjacent piriform cortex, rather than vStr itself. This provides a novel interpretation of previous rodent work on gamma oscillations in the vStr and related circuits, and an important consideration for future work seeking to use oscillations in these areas as biomarkers in rodent models of human behavioral and neurological disorders.

neuroscience↗