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Leibold, C.

Publications and source records attributed to Leibold, C..

17 recordsLinked to original sources

Stimulus and circuit contributions to the information geometry of neural manifolds

Understanding how network connectivity shapes neural representations is central to systems neuroscience. While dimensionality reduction methods uncover low-dimensional manifold structure in population recordings, a rigorous framework connecting manifold geometry to network mechanisms and information encoding remains lacking. We develop a differential geometric approach for analyzing neural manifolds in rate-based recurrent networks receiving tuned feedforward inputs. We derive expressions for the pullback metric of neural manifolds, showing how input tuning curves together with feedforward and recurrent synaptic connectivity shape manifold geometry. Critically, we establish that the Fisher information matrix at steady states also has the structure of a pullback metric, directly linking intrinsic manifold geometry to stimulus discriminability and information encoding. For noise with slow temporal correlations propagated through the network, we show that recurrent effects on information geometry cancel: Fisher information depends only on the feedforward connectivity. Thus, feedforward connectivity critically determines representational geometry. We apply our approach to the representation of space by a module of hexagonal grid cells. We first demonstrate that the representation is approximately isometric for a random distribution of grid phases. Moreover, a linear feedforward transformation can map spatially random input tuning curves into a population of hexagonal grid cells, generating a toroidal neural manifold. Thus, feedforward connectivity alone can generate structured spatial representations without requiring carefully tuned recurrent connectivity or continuous attractor dynamics. Recurrent connectivity, however, is shown to improve stimulus encoding under fast noise, thereby implementing a selective noise reduction.

neuroscience↗

Comparison of place field detection methods and their effect on place field stability and drift in mouse dCA1.

BackgroundHippocampal place cells (PCs) undergo representational drift, i.e., a gradual change in their place fields despite unaltered behavior. While Ca2+ imaging enables long-term tracking of PC populations, distinct PC detection methods have been shown to yield different subpopulations of PCs, with only a few systematic comparisons between methods, especially in open arenas. New MethodWe provide an analysis protocol for one-photon PC data obtained during free foraging in two-dimensional arenas that allows us to compare two widely used PC detection methods, significance of spatial information (SI), and split-half correlation (SHC), and their effect on representational drift. The analysis is demonstrated on previously published Ca2+ data from dorsal CA1 of freely foraging mice, with cells tracked for 10 consecutive days. ResultsBoth criteria, SI and SHC, yielded proportions of approx. 17% PCs with only 40% overlap. SI-identified PCs demonstrated higher stability, higher rate map correlations, and a slower rate of representational drift than SHC-PCs. Comparison with existing methodsPrevious studies comparing SI and SHC PC detection methods in Ca2+ data did not focus on either open field behavior or representational drift. ConclusionOur results indicate that the choice of PC detection method significantly affects the estimate of representational drift in Ca2+ imaging studies.

neuroscience↗

Differential contribution of HCN1 and HCN4 to the synchronisation of sinoatrial pacemaker cells

The hearts ability to beat with high precision, with a regular and steady rhythm relies on the synchronised activity of pacemaker cells in the sinoatrial node (SAN), which communicate with one another through gap junctions. This process ensures that electrical impulses are organised and reach a critical mass to ignite the electrical activity of the surrounding atrial tissue and trigger the regular heartbeat. HypothesisWe hypothesise that hyperpolarisation-activated, cyclic nucleotide-gated (HCN) channels play a pivotal role in maintaining this synchronisation process. This idea aligns with the well-established role of HCN channels in stabilising the membrane potential in the voltage range of the slow diastolic depolarisation, counteracting voltage fluctuations and effectively filtering out variations in the beating rate from neighbouring cells. AimWe focus on two specific HCN channel subtypes--HCN1 and HCN4--and their contributions to the rapid synchronisation of pacemaker cells, a phenomenon known as phasic entrainment. Using two HCN channel-mutant mouse models, we dissect the distinct roles of HCN1 and HCN4 in this process. MethodsWe employed patch-clamp electrophysiology to determine phase response curves (PRCs) to predict the ability of single cells to interact in the SAN. Using computer simulations, the behaviour of the SAN at the network level was determined. ResultsWe found that HCN1, but not HCN4, is essential for the fast synchronisation of pacemaker cells in the SAN and propose a mechanism by which HCN1 channels regulate this process. ConclusionThese findings highlight HCN1 as a critical component for ensuring the precise and rapid coordination needed for synchronisation of the SAN, for a regular and consistent heartbeat. Translational perspectiveOur work provides essential insights into the cellular and molecular mechanisms governing SAN function and lays the groundwork for several clinically relevant applications. Understanding how If blockers may affect heart rate and rhythm stability is crucial for assessing potential side effects of current and future subtype-specific HCN channel inhibitors. Moreover, our findings could support new diagnostic strategies for detecting patients at risk of SAN dysfunction. Ultimately, these findings pave the way for innovative therapeutic approaches, including targeted channel modulation and future cell or gene therapies to restore pacemaker stability.

physiology↗

Formation of Task Representations and Replay in Mouse Medial Prefrontal Cortex

The medial prefrontal cortex (mPFC) is thought to support cognitive flexibility by forming and maintaining generalized representations of abstract tasks. The formation of these representations as well as their relation to preexisting representations of contextual or spatial information is incompletely understood. In this study, we analyzed longitudinal 1-photon calcium recordings in mice performing an olfaction-guided spatial memory task over an eight-week period that included habituation, training, and sleep epochs. Our results reveal that, while a minority of neurons initially conveyed significant information about the behavior of the animal, the bulk of task-related activity only emerged after the animals reached proficient performance. Although goal arm information is robustly represented at both the single-cell and network levels both during learning and in task proficient mice, it undergoes significant remapping throughout the learning process. Additionally, we identified the establishment of recurring sequences during learning and their replay at reward locations, with no evidence of them existing during odor sampling phase, during sleep or before training. Conversely, during odor sampling, information about odor identity is robustly available in the rate coactivation patterns, even before animals reached task proficiency. These findings suggest that the mPFC predominantly establishes generalized task representations de novo during learning, relying only minimally on preexisting spatial representations and that sub-second neural sequences in the mPFC are more likely involved in evaluating behavioral outcomes rather than planning future actions.

neuroscience↗

A mammalian inferior colliculus model for sound source separation using interaural time differences

The inferior colliculus (IC) is a central hub in the ascending auditory brainstem. It hosts many neurons tuned to interaural time differences (ITDs). ITD tuning, however, is already observed and generated one synapse upstream in the superior olivary complex and the physiological mechanisms as well as the functional purpose of the IC projection remain partially unresolved. Here, we argue that combining ITD sensitive inputs from medial superior olive (MSO) and lateral superior olive (LSO) requires a temporally well adjusted delay of cross-hemispheric fibers from LSO to IC, given the fast synaptic kinetics of IC neurons. We present a normative model of the midbrain auditory circuitry that finds an optimal cross-hemispheric delay of 0.3 cycles and optimal synaptic strengths by maximizing the firing rate of IC neurons for a stimulus at a given ITD. The model suggests that, by varying the relative synaptic weight of MSO and LSO input, individual neurons are optimized to transmit information of all sound sources in a complex auditory scene. ITD tuning of IC neurons would then results as a side effect. The model focuses on the low-frequency range, is consistent with the distribution of best ITDs observed in experimental recordings and performs close to optimal in sound source reconstruction. Author SummaryNatural acoustic scenes consist of many spatially distributed and concurrently active sound sources. We show how such concurrent sounds can be optimally reconstructed solely using information about interaural arrival time differences. We argue that this optimal solution is almost matched by a neural circuit model inspired by the ascending auditory pathway. The model is computationally very efficient because changing only one synaptic weight moves the azimuthal focus of a midbrain neuron. The model predicts a universal phase delay of cross-hemispheric delay lines in the ascending auditory brainstem.

neuroscience↗

Prefrontal orchestration: a cortical network for rodent motor inhibition

Goal-directed action control and behavioral flexibility are prerequisites for effective, adaptive behavior. Both abilities rely on functional motor inhibition, which is linked to the prefrontal cortex (PFC), where distinct subsections collaborate in functional networks. How these PFC subsections interact and which roles they play during motor inhibition remains incompletely understood. In this study, we employed an action-preparation task in rats, combined with bidirectional optogenetic interventions, opto-fMRI, single unit electrophysiology and local field potential synchrony measurements across PFC subsections. Our findings support a clear and simple model of action inhibition within the prefrontal network. This model suggests prelimbic cortex (PL) as an input-dependent switch between motor inhibition and execution, modulated by an infralimbic cortex (IL)-dominated network. This distribution of tasks allows the PL to mediate goal-directed action while the IL ensures behavioral flexibility. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=137 SRC="FIGDIR/small/618207v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@147ab98org.highwire.dtl.DTLVardef@52b6f9org.highwire.dtl.DTLVardef@6ab566org.highwire.dtl.DTLVardef@1ab5044_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical Abstract:C_FLOATNO Behavioral measurements were conducted alongside optogenetic modulation of PL, IL or VO. Inhibitory modulation led to varying effects on performance, while excitatory ChR2 stimulation of PL, IL or VO led to analogous effects on proactive motor inhibition. To identify shared nodes recruited by ChR2 stimulation of distinct PFC subareas, we performed whole-brain mapping with opto-fMRI. This revealed an overlapping activation volume spanning PFC, BF, Fr, Cg2, and M2. Notably, this common activation volume closely outlined the entirety of the IL-recruited regions; IL excitation also produced robust behavioral effects. Multisite recordings revealed task performance-dependent PL-IL delta synchrony. PCA of single-unit activity during behavior revealed varied neural patterns among PFC subsections, highlighting PL to have the most the homogenous input-driven activity. The findings can be interpreted as PL acting as an input-dependent switch between motor inhibition and execution, modulated by IL to maintain behavioral flexibility. C_FIG

neuroscience↗

The Dynamics of Context-Dependent Space Representations in AC

Auditory space is not mapped onto the receptor surface in the inner ear but results from complex neuronal computations by our brain. However, there is no consensus about the resulting neuronal representation of space in auditory cortex (AC) owing to contradicting reports: While many studies found a tuning preference for sound source positions in the contralateral hemisphere, others have observed an additional population of cells tuned to midline positions or even context-dependent dynamic changes in the tuning of individual cells. A fundamental difference across studies was the animals brain state, which might affect AC processing and thus the apparent nature of its spatial code. Yet no study to date investigated spatial tuning of identified AC neurons across brain states. Here, we employed longitudinal two-photon calcium imaging in the AC of mice under distinct states of wakefulness: anesthetized, idle awake, and during involvement in a go/no-go localization task. We find that previously reported differences in coding regimes are directly linked to wakefulness: A strong contralateral tuning bias is present under anesthesia, while pronounced and stable mid-line tuning appeared in awake but idle animals. Intriguingly, in localizing mice, tuning was different again with a large proportion of AC neurons responding to the position of the currently relevant sound-source. These population regimes remained stable across imaging sessions despite the spatial tuning of individual neurons being highly variable. Our findings resolve apparent contradictions in the literature and thus give a dynamical explanation for the multiple space representations in the AC.

neuroscience↗

A Theory of Hippocampal Theta Correlations

Hippocampal place cell sequences have been hypothesized to serve as diverse purposes as the induction of synaptic plasticity, formation and consolidation of long-term memories, or navigation and planning. During spatial behaviors of rodents, sequential firing of place cells at the theta timescale (known as theta sequences) encodes running trajectories, which can be considered as 1-dimensional behavioral sequences of traversed locations. In a 2-dimensional space, however, each single location can be visited along arbitrary 1-dimensional running trajectories. Thus, a place cell will generally take part in multiple different theta sequences, raising questions about how this 2-dimensional topology can be reconciled with the idea of hippocampal sequences underlying memory of (1-dimensional) episodes. Here, we propose a computational model of cornu ammonis 3 (CA3) and dentate gyrus (DG), where sensorimotor input drives the direction-dependent (extrinsic) theta sequences within CA3 reflecting the 2-dimensional spatial topology, whereas the in-trahippocampal CA3-DG projections concurrently produce intrinsic sequences that are independent of the specific running trajectory. Consistent with experimental data, these intrinsic theta sequences are less prominent in the theta state, but we show that they can nevertheless be detected during theta activity, thereby serving as running-direction independent landmark cues. We hypothesize that the intrinsic sequences largely reflect replay and preplay activity during non-theta states.

neuroscience↗

Low Rate Hippocampal Delay Period Activity Encodes Behavioral Experience

Remembering what just happened is a crucial prerequisite to form long-term memories but also for establishing and maintaining working memory. So far there is no general agreement about cortical mechanisms that support short-term memory. Using a classifier-based decoding approach, we report that hippocampal activity during few sparsely distributed brief time intervals contains information about the previous sensory motor experience of rodents. These intervals are characterized by only a small increase of firing rate of only a few neurons. These low-rate predictive patterns are present in both working memory and non-working memory tasks, in two rodent species, rats and Mongolian gerbils, are strongly reduced for rats with medial entorhinal cortex lesions, and depend on the familiarity of the sensory-motor context.

neuroscience↗

Distinct spatial maps and multiple object codes in the lateral entorhinal cortex

The lateral entorhinal cortex (LEC) is a major cortical input area to the hippocampus and it is crucial for associative object-place-context memories. An unresolved question is whether these associations are performed exclusively in the hippocampus or also upstream thereof. Anatomical evidence suggests that the LEC processes both object and spatial information. We here describe a gradient of spatial selectivity along the antero-posterior axis of the LEC. We demonstrate that the LEC generates distinct spatial maps for different contexts that are independent of object coding and vice versa, thus providing evidence for pure spatial and pure object codes upstream of the hippocampus. Whilst space and object coding occur by and large separately in the LEC, we identified neurons that encode for space and objects conjunctively. Together, these findings point to a scenario in which the LEC sustains both distinct space and object coding as well as associative space-object coding.

neuroscience↗

Distinct roles of dentate gyrus and medial entorhinal cortex inputs for phase precession and temporal correlations in hippocampal CA3 place cells

The hippocampal CA3 subregion is a densely connected recurrent circuit that supports memory consolidation and retrieval by generating and storing sequential neuronal activity patterns that reflect recent experience. While theta phase precession is thought to be critical for generating sequential activity during memory encoding, the circuit mechanisms that support this computation across hippocampal subregions are unknown. By analyzing CA3 network activity in the absence of each of its theta modulated excitatory inputs, we show necessary and unique contributions of the dentate gyrus (DG) and the medial entorhinal cortex (MEC) to phase precession. DG inputs are essential for generating the preferential spiking of CA3 cells during late theta phases and for organizing the temporal order of neuronal firing, while MEC inputs modulate the general precision of phase precession. A computational model that accounts for the empirical findings suggests that DG inputs affect the phase and MEC inputs affect the amplitude of inhibitory subnetworks. Our results thus identify a novel and unique functional role of the DG for the generation of sequence coding in the CA3 recurrent circuit.

neuroscience↗

Neural Kernels for Recursive Support Vector Regression as a Model for Episodic Memory

Retrieval of episodic memories requires intrinsic reactivation of neuronal activity patterns. The content of the memories are thereby assumed to be stored in synaptic connections. This paper proposes a theory in which these are the synaptic connections that specifically convey the temporal order information contained in the sequences of a neuronal reservoir to the sensory-motor cortical areas that give rise to the subjective impression of retrieval of sensory motor events. The theory is based on a novel recursive version of support vector regression that allows for efficient continuous learning that is only limited by the representational capacity of the reservoir. The paper argues that hippocampal theta sequences are a potential neural substrate underlying this reservoir.The theory is consistent with confabulations and post-hoc alterations of existing memories.

neuroscience↗

Directional Tuning of Phase Precession Properties in the Hippocampus

Running direction in the hippocampus is encoded by rate modulations of place field activity but also by spike timing correlations known as theta sequences. Whether directional rate codes and the directionality of place field correlations are related, however, has so far not been explored and therefore the nature of how directional information is encoded in the cornu ammonis remains unresolved. Here, using a previously published dataset that contains the spike activity of rat hippocampal place cells in the CA1, CA2 and CA3 subregions during free foraging of male Long-Evans rats in a 2D environment, we found that rate and spike timing codes are related. Opposite to a place fields preferred firing rate direction spikes are more likely to undergo theta phase precession and, hence, more strongly impact paired correlations. Furthermore, we identified a subset of field pairs whose theta correlations are intrinsic in that they maintain the same firing order when the running direction is reversed. Both effects are associated with differences in theta phase distributions, and are more prominent in CA3 than CA1. We thus hypothesize that intrinsic spiking is most prominent when the directionally modulated sensory-motor drive of hippocampal firing rates is minimal, suggesting that extrinsic and intrinsic sequences contribute to phase precession as two distinct mechanisms.

neuroscience↗

Pupil size dynamics predict dLGN firing mode over a wide range of timescales

The processing of sensory information, even at early processing stages, is influenced by the internal state of the animal. Internal states, such as arousal, are often characterized by relating neural activity to a single "level" of arousal, defined by a behavioral indicator such as pupil size. In this study, we expand the understanding of arousal-related modulations in sensory systems by uncovering multiple timescales of pupil dynamics and their relationship to neural activity. Specifically, we observed coupling between spiking activity in the mouse dorsal lateral geniculate nucleus (dLGN) of the thalamus and pupil dynamics across timescales spanning three orders of magnitude, from seconds to minutes. Throughout all of these timescales, two distinct spiking patterns - tonic spikes and bursts - preferred opposing phases of pupil dynamics. This multi-scale coupling captures modulations distinct from those captured by pupil size per se, transitions between locomotion and quiescence, or saccadic eye movements. Furthermore, coupling persisted even during viewing of a naturalistic movie, where it contributed to differences in how visual information was encoded. We conclude that dLGN spiking activity is influenced by arousal processes associated with pupil dynamics occurring simultaneously across a broad range of timescales, with implications for the transfer of sensory information to the cortex.

neuroscience↗

The effect of boundaries on grid cell patterns

Mammalian grid cells represent spatial locations in the brain via triangular firing patterns that tessellate the environment. They are regarded as the biological substrate for path integration thereby generating an efficient code for space. However, grid cell patterns are strongly influenced by environmental manipulations, in particular exhibiting local geometrical deformations and defects tied to the shape of the recording enclosure, challenging the view that grid cells constitute a universal code for space. We show that the observed responses to environmental manipulations arise as a natural result under the general framework of feedforward models with spatially unstructured feedback inhibition, which puts the development of triangular patterns in the context of a Turing pattern formation process over physical space. The model produces coherent neuronal populations with equal grid spacing, field size, and orientation. PACS numbers87.19.lv,87.10.Ed,02.30.Jr

neuroscience↗

A Model for Navigation in Unknown Environments Based on a Reservoir of Hippocampal Sequences

Hippocampal place cell populations are activated in sequences on multiple time scales during active behavior, resting and sleep states, suggesting that these sequences are the genuine dynamical motifs of the hippocampal circuit. Recently, prewired hippocampal place cell sequences have even been reported to correlate to future behaviors, but so far there is no explanation of what could be the computational benefits of such a mapping between intrinsic dynamical structure and external sensory inputs. Here, I propose a computational model in which a set of predefined internal sequences is used as a dynamical reservoir to construct a spatial map of a large unknown maze based on only a small number of salient landmarks. The model is based on a new variant of temporal difference learning and implements a simultaneous localization and mapping algorithm. As a result sequences during intermittent replay periods can be decoded as spatial trajectories and improve navigation performance, which supports the functional interpretation of replay to consolidate memories of motor actions.

neuroscience↗

Hippocampal Spike-Timing Correlations Lead to Hexagonal Grid Fields

Space is represented in the mammalian brain by the activity of hippocampal place cells as well as in their spike-timing correlations. Here we propose a theory how this temporal code is transformed to spatial firing rate patterns via spike-timing-dependent synaptic plasticity. The resulting dynamics of synaptic weights resembles well-known pattern formation models in which a lateral inhibition mechanism gives rise to a Turing instability. We identify parameter regimes in which hexagonal firing patterns develop as they have been found in medial entorhinal cortex.

neuroscience↗