Biology subjects

Maler, L.

Publications and source records attributed to Maler, L..

10 recordsLinked to original sources

bioRxiv2026

Clustered heterogeneity, spiking history and efficient silencing maximize mutual information in adaptive time encoding

Neurons involved in a computation are remarkably diverse. They display a range of thresholds, time scales and spiking history dependence, and often exhibit adaptation that enhances computational power by concentrating spikes at transient stimuli. We seek basic organizational principles for coding with cellular heterogeneity by focusing on the encoding and retrieval of inter-event time interval sequences by adaptive neurons. We formulate the general input-output mutual information maximization problem for parallel neurons with a fading memory of past intervals. The solution reveals an unexpected multi-variate heterogeneity that is tailored to encode information efficiently. Gradient ascent on mutual information produces a number of parameterized clusters bounded by the sequence length. Correlations between parameters emerge naturally. The predicted covariation of adaptation time with spiking history strength, and the optimal combination of history and non-history cells, agree with experiments. Threshold optimization yields a continuum of time constants and thresholds within each cluster. Strikingly, division of labour between neurons arises where subsets respond selectively to different interval ranges. This creates cell-specific interval ranges that tile reasonably well a uniform prior of intervals, and almost perfectly a scale-free prior, producing a code that is efficient in cell number and reduces metabolic cost by limiting spike rates.

neuroscience↗

bioRxiv2026

Multimodal reference brain atlas of adult Danionella cerebrum

Mechanistic accounts of brain function require a common coordinate system in which structural, molecular and functional data can be integrated and compared across individuals. The teleost genus Danionella is unique among vertebrates in retaining lifelong transparency, allowing non-invasive, cellular-resolution functional imaging across the entire adult brain. A reference atlas in this model would therefore provide a strong foundation for causal and comparative circuit studies. Here we present an integrated anatomical, molecular and functional reference brain for adult Danionella cerebrum as a standardised atlas resource. Using a transgenic nuclear fluorescence marker, whole-mount tissue clearing and high-resolution two-photon microscopy, we generated an average reference brain from 21 adult fish to create a common coordinate system. Whole-mount in situ hybridisation for 29 neuronal markers, complemented by tract annotation from structural imaging and tracer injections, enabled us to segment 203 neuroanatomical regions. We found pronounced sex differences in telencephalic, cerebellar and hindbrain nuclei, revealing sexually dimorphic organisation across multiple brain regions. All data and segmentations are made openly accessible, providing a community resource for studies of circuit function, molecular makeup and sexual dimorphism in an optically accessible adult vertebrate brain.

neuroscience↗

bioRxiv2026

Brain-wide hierarchical and sexually dimorphic tuning for social vocalizations

Vocal repertoires consist of a limited number of call types, even though their sounds can vary continuously in form. Where in the brain receivers partition this variation into discrete types is contested: different accounts place the emergence of categories in the cortex/pallium or already in the midbrain. Because recordings have been limited to isolated regions, it remains unknown whether this partitioning is confined to a single region at all, occurs in parallel across many, or is built up along the pathway. Here we present the first whole-brain, cellular-resolution analysis of how conspecific vocalizations are categorized in a vertebrate, using the glassfish Danionella cerebrum. We find that categorization is neither pallial nor localized. It begins at the first central auditory nuclei, much earlier than previously thought, where a continuous morph between social and non-social sounds evokes an abrupt switch in population activity. The midbrain then sharpens these representations, and the thalamus filters for species-typical pulse rates while splitting call duration into two discrete populations. Only downstream of this shared code do the sexes diverge in forebrain social nuclei. Call type partitioning is thus distributed and hierarchically assembled, rather than read out at any one stage.

neuroscience↗

bioRxiv2024

Functional separation of long-range inputs by intrinsic dynamics of dorsal raphe 5-HT neurons

Monoaminergic nuclei such as the serotonergic dorsal raphe nucleus (DRN) receive synaptic inputs containing functionally distinct streams of information, yet the dimensionality of the resulting output population code and its cellular underpinning are currently unknown. By combining electrophysiological and computational approaches, here we uncover separable neural encoding of two excitatory inputs conveying disjunct information to DRN 5-HT neurons - the lateral habenula (LHb) and medial prefrontal cortex (mPFC). Dual-color opsin strategies revealed that a population of 5-HT neurons receive inputs from both mPFC and LHb. Subthreshold excitatory postsynaptic potentials triggered by both inputs were largely indistinguishable, yet suprathreshold spiking behavior exhibited input-specific latencies and dispersion statistics. A support vector machine classifier demonstrated that input identity can be accurately decoded from spike timing, but not subthreshold events, of under ten 5-HT neurons. Upon examining the intrinsic cellular mechanisms in 5-HT neurons that couple EPSPs to spiking dynamics, we uncovered two likely candidate mechanisms: a low-threshold calcium conductance that selectively boosts slow excitatory inputs, and a subthreshold, voltage-dependent membrane noise that generates variation of spike latency and jitter. Stochastic simulations suggest that these two intrinsic properties of 5-HT neurons are sufficient to transform LHb and mPFC inputs into distinct output spiking patterns. These results reveal that hub-like networks like the DRN can segregate distinct informational streams by a cell-intrinsic mechanism. The resulting emergent population spike synchrony code provides a means for the DRN to widely broadcast these streams as a multiplexed signal. Significance statementPhylogenetically old neuromodulatory systems in the brain, such as the serotonergic dorsal raphe nucleus, are compact yet richly innervated structures. Here, we use the raphe as a testbed to ask how distinct informational sources to hub-like networks are processed or integrated into a coherent neural code. Using electrophysiological and computational methods, including biophysically grounded stochastic simulations, we find that intrinsic noise mechanisms in serotonergic neurons are critical to transform approximately matched subthreshold excitation into distinct spike timing profiles. Thus, cell-intrinsic noise mechanisms can effectively synthesize a spike synchrony code that, we hypothesize, multiplexes input information to hub-like networks at the population level even in the absence of strong local circuit interactions.

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bioRxiv2023

Mice can learn a cognitive map based on a stable start location and self-motion signals

Animals navigate by learning the spatial layout of their environment. We investigated spatial learning of mice in an open maze where food was hidden in one of a hundred holes. Mice leaving from a stable entrance learned to efficiently navigate to the food without the need for landmarks. We developed a quantitative framework to reveal how the mice estimate the food location based on analyses of trajectories and active hole checks. After learning, the computed "target estimation vector" (TEV) closely approximated the mices route and its hole check distribution. The TEV required learning both the direction and distance of the start to food vector, and our data suggests that different learning dynamics underlie these estimates. We propose that the TEV can be precisely connected to the properties of hippocampal place cells. Finally, we provide the first demonstration that, after learning the location of two food sites, the mice took a shortcut between the sites, demonstrating that they had generated a cognitive map.

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bioRxiv2022

Dentate gyrus mossy cells exhibit sparse coding via adaptive spike threshold dynamics

Hilar mossy cells (hMCs) are glutamatergic neurons in the dentate gyrus (DG) that receive inputs primarily from DG granule cells (GCs), CA3 pyramidal cells and local inhibitory interneurons. The hMCs then provide direct excitatory and disynaptic inhibitory feedback input to GCs. Behavioral and in vivo single unit recording experiments have implicated hMCs in pattern separation as well as is in spatial navigation and learning. It has, however, been difficult to mechanistically link the in vivo physiological behavior of hMCs with their intrinsic excitability properties that convert their synaptic inputs into spiking output. Here, we carried out electrophysiological recordings from the main cell types in the DG and found that hMCs displayed a highly adaptive threshold acting over a remarkably protracted time-scale. The hMC spike threshold increased linearly with increasing current stimulation and saturated at high current intensities. This threshold also increased in response to spiking and this effect also decayed over a long timescale, allowing for activity-dependent summation that limited hMC firing rates. This mechanism operates in parallel with a prominent medium after-hyperpolarizing potential (AHP) generated by the small conductance K+ channel. Based on experimentally derived parameters, we developed a phenomenological exponential integrate-and-fire model that closely mimics the hMC adaptive threshold. This lightweight model is amenable to its incorporation into large network models of the DG that will be conducive to deepen our understanding of the neural bases of pattern separation, spatial learning and navigation in the hippocampus. Statement of significanceRecent studies on hilar mossy cells have revealed that they are implicated in spatial navigation and mnemonic functions. Yet, the basic intrinsic characterization of these hMCs is still too superficial to explain their spiking behavior in vivo. Here, we describe novel biophysical properties of hMCs, including an independent relationship between spike latency and spike threshold as well as a slowly adapting spike threshold. These findings complement several other biophysical and connectivity similarities between hMCs and CA3 pyramidal cells, while emphasizing the contrast with hilar interneurons. Additionally, our results are well captured by a phenomenological model of the hMC which provides a useful framework to study the neural substrate of spatial navigation and learning in the dentate gyrus.

neuroscience↗

bioRxiv2021

Mixed selectivity coding of sensory and motor social signals in the thalamus of a weakly electric fish

Recent studies have shown that high-level neural activity often exhibits mixed selectivity to multivariate signals. How such representations arise and how they modulate natural behavior is poorly understood. The social behavior of weakly electric fish is relatively low-dimensional and easily reproduced in the laboratory. Here we show how electrosensory signals related to courtship and rivalry in Apteronotus leptorhynchus are represented in the preglomerular nucleus, the thalamic region exclusively connecting the midbrain with the pallium. We show that preglomerular cells convert their midbrain inputs into a mixed selectivity code that includes corollary discharge of outgoing communication signals. We discuss how the preglomerular pallial targets might use these inputs to control social behavior and determine dominance in male-male competition and female mate selection during courtship. Our results showcase the potential of the electrocommunication system as an accessible model for studying the neural substrates of social behavior and principles of multi-dimensional neural representation.

neuroscience↗

bioRxiv2019

Cellular and network mechanisms may generate sparse coding of sequential object encounters in hippocampal-like circuits

In mammals, the localization of distinct landmarks is performed by hippocampal neurons that sparsely encode an animals location relative to surrounding objects. Similarly, the dorsal lateral pallium (DL) is essential for spatial learning in teleost fish. The DL of weakly electric gymnotiform fish receives sensory inputs from the preglomerular nucleus (PG), which has been hypothesized to encode the temporal sequence of electrosensory or visual landmark/food encounters. Here, we show that DL neurons have a hyperpolarized resting membrane potential combined with a high and dynamic spike threshold that increases following each spike. Current-evoked spikes in DL cells are followed by a strong small-conductance calcium-activated potassium channel (SK) mediated after-hyperpolarizing potential (AHP). Together, these properties prevent high frequency and continuous spiking. The resulting sparseness of discharge and dynamic threshold suggest that DL neurons meet theoretical requirements for generating spatial memory engrams by decoding the landmark/food encounter sequences encoded by PG neurons.

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bioRxiv2018

Neural activity in a hippocampus-like region of the teleost pallium are associated with navigation and active sensing

Neural mechanisms underlying spatial navigation in fish are unknown and little is known, for any vertebrate, about the relationship between active sensing and the formation of spatial maps. The weakly electric fish, Gymnotus Carapo, uses their active electric sense for spatial navigation. The electric organ discharge rate (EODr) undergoes transient increases during navigation to enhance electrosensory sampling. Gymnotus also uses stereotyped forward/ backward swimming as a second form of active sensing that brings objects towards the electroreceptor-dense head region. We wirelessly recorded neural activity from the pallium of freely swimming Gymnotus. Spiking activity was sparse and occurred only during swimming. Notably, some units exhibited significant place specificity and/or association with both forms of active sensing. Our results provide the first characterization of neural activity in a hippocampal-like region of a teleost fish brain and connects active sensing via sensory sampling rate and directed movements to higher order encoding of spatial information.

neuroscience↗

bioRxiv2018

A novel time-stamp mechanism transforms egocentric encounters into an allocentric spatial representation

Learning the spatial organization of the environment is essential for most animals survival. This often requires the animal to derive allocentric information about the environment from egocentric sensory and motor experience. The neural circuits and mechanisms underlying this transformation are currently unknown. We addressed this problem in electric fish, which can precisely navigate in complete darkness and whose requisite brain circuitry is relatively simple. We conducted the first neural recordings in the preglomerular complex, the thalamic region exclusively connecting the optic tectum with the spatial learning circuits in the dorsolateral pallium. While tectal egocentric information was eliminated in preglomerular neurons, the time-intervals between object encounters were precisely encoded. We show that this highly-reliable temporal information, combined with a speed signal, can permit accurate path-integration that then enables computing allocentric spatial relations. Our results suggest that similar mechanisms are involved in spatial learning via sequential encounters in all vertebrates.

neuroscience↗