Biology subjects

Haider, B.

Publications and source records attributed to Haider, B..

12 recordsLinked to original sources

bioRxiv2025

A standardized and reproducible behavioral protocol to elicit visual spatial attention in mice

Understanding how neural activity gives rise to cognitive processes such as selective attention is a fundamental goal of neuroscience. An important but often overlooked advance towards this goal requires the development and sharing of rigorous and reproducible behavioral tasks across labs; this is particularly important given the recent surge in studies of cognition and perception in mice. Here, we developed a standardized training protocol for head-fixed mice to become experts in a psychometric visual contrast detection task in just 17 days. Experts detected stimuli at two distinct spatial locations for several hundred trials per day. As consecutive trials elapsed at either location, the speed, accuracy, and contrast sensitivity of visual perception improved - all hallmarks of spatial attention improving performance, as seen in primates. These findings validate the efficacy of this protocol to reveal multiple aspects of selective spatial attention in mice, establishing a rigorous and reproducible tool for the community.

neuroscience↗

bioRxiv2025

Single Capture Quantitative Oblique Back-Illumination Microscopy

Quantitative oblique back-illumination microscopy (qOBM) has emerged as a powerful technique for label-free, 3D quantitative phase imaging of arbitrarily thick biological specimens. However, in its initial embodiment, qOBM requires multiple captures for phase recovery, which reduces imaging speed and increases system complexity. In this work, we present a novel advancement in qOBM: single-capture qOBM (SCqOBM) which utilizes a deep learning model to accurately reconstruct phase information from a single oblique back-illumination capture. We demonstrate that SCqOBM achieves remarkable phase imaging accuracy, closely matching the results of traditional four-capture qOBM in diverse biological samples. We first highlight the unique potential of SCqOBM for non-invasive, in-vivo imaging applications by visualizing blood flow in mouse brain and human arm. Additionally, we demonstrate single-slice (en-face) quantitative phase imaging at 2 kHz and volumetric refractive index tomography at speeds up to 10 volumes per second. SCqOBM offers transformative advantages in speed, simplicity, and system accessibility, making it highly suitable for dynamic and real-time imaging applications. Its ability to produce high-resolution, quantitative phase and refractive index images with minimal hardware complexity opens new frontiers in biomedical research and clinical diagnostics, including non-invasive hematological assessments and in-vivo tissue imaging.

bioengineering↗

bioRxiv2025

NeuroSuite for Long-term Functional and Structural Studies of Air-Liquid Interface Cerebral Organoids

Over the past decade, air-liquid interface cerebral organoids (ALI-COs) have emerged as powerful in vitro models that capture essential structural and functional traits of the human brain, offering an exciting alternative to traditional animal models in neuroscience. Yet, the full potential of these systems has remained untapped due to the lack of non-invasive, long-term electrophysiological tools capable of preserving organoid integrity. Existing techniques, ranging from patch clamping to rigid and 3D microelectrode arrays, often compromise organoid growth and disrupt delicate cytoarchitecture. Here, we present NeuroSuite, an innovative bioelectronic platform designed to overcome these challenges. At its core is Neuroweb, a perforated, ultra-thin, and conformable organic microelectrode array engineered for minimal disruption of nutrient and oxygen exchange. Neuroweb is reusable and supports stable recordings for over six months, making it uniquely suited for longitudinal studies. Coated with poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS), a high-performance mixed ionic-electronic conductor, Neuroweb delivers exceptional signal-to-noise ratio recordings with high spatial precision. By pairing Neuroweb with NeuroMaps, an intuitive software for interactive analysis and visualisation, NeuroSuite enables long-term, non-invasive tracking and spatial mapping of electrical activity from brain organoids and ex vivo brain slices at the air-liquid interface. Following rigorous validation, we demonstrate that NeuroSuite can capture both high- and low-frequency throughout maturation. Our pipeline reveals evolving network connectivity, including the development of GABA-ergic interneurons, and concurrent shifts in high-frequency spiking and low-frequency oscillations indicative of a refinement in the excitatory-inhibitory balance. Finally, automated data acquisition and spatial spike mapping highlight local activity changes in response to media composition, a factor often overlooked in conventional recordings. NeuroSuite thus opens a new frontier in organoid neuroscience, enabling precise, long-term monitoring essential for modelling neurological diseases, understanding human brain development, and accelerating drug discovery. TeaserConformal organic bioelectronic arrays, combined with an open-access toolbox for analysis and visualisation, reveal real-time and long-term neural dynamics in brain organoid slices at the air-liquid interface.

neuroscience↗

bioRxiv2025

Highly selective visual receptive fields in mouse frontal cortex

A hallmark of the mammalian visual system is spatial information processing. This relies on feedforward activity spanning multiple brain areas, and on interconnected neurons with spatial receptive fields (RFs) aligned across these areas. This organization allows neurons to iteratively analyze information from the same point of the visual field. It remains unclear if this framework extends beyond the visual system, especially into cognitive areas of frontal cortex that exert feedback control over early sensory areas. Here, we surveyed the mouse frontal cortex (anterior cingulate and secondary motor areas), and discovered neurons with low latency, highly localized visual RFs. Just like in visual cortex, responses were often highly selective for bright or dark stimuli. The responses lagged visual cortical areas by only [~]25 ms, and their RFs were comparable in size. Further, the representation of visual space in frontal cortex showed a strong bias for the central (binocular) visual field, but there was no evidence of a topographically organized retinotopic map. Importantly, these visual responses were abolished by optogenetic silencing of visual cortex, revealing a causal role for feedforward hierarchical connectivity that extends visual spatial processing directly into motor and cognitive regions of mouse frontal cortex.

neuroscience↗

bioRxiv2024

Environmental context sculpts spatial and temporal visual processing in thalamus

Behavioral state modulates neural activity throughout the visual system1-3. This is largely due to changes in arousal that alter internal brain state4-10. Much is known about how these internal factors influence visual processing7-11, but comparatively less is known about the role of external environmental contexts12. Environmental contexts can promote or prevent certain actions13, and it remains unclear if and how this affects visual processing. Here, we addressed this question in the thalamus of awake head-fixed mice while they viewed stimuli but remained stationary in two different environmental contexts: either a cylindrical tube, or a circular running wheel that enabled locomotion. We made silicon probe recordings in the dorsal lateral geniculate nucleus (dLGN) while simultaneously measuring multiple metrics of arousal changes, so that we could control for them across contexts. We found surprising differences in spatial and temporal processing in dLGN across contexts. The wheel context (versus tube) showed elevated baseline activity, and faster but less spatially selective visual responses; however, these visual processing differences disappeared if the wheel no longer enabled locomotion. Our results reveal an unexpected influence of the physical environmental context on fundamental aspects of early visual processing, even in otherwise identical states of alertness and stillness.

neuroscience↗

bioRxiv2024

Machine learning-based spike sorting reveals how subneuronal concentrations of monomeric Tau cause a loss in excitatory postsynaptic currents in hippocampal neurons

Extracellular recordings of neuronal activity constitute a powerful tool for investigating the intricate dynamics of neural networks and the activity of individual neurons. Microelectrode arrays (MEAs) allow for recordings with a high electrode count, ranging from 10s to 1000s, generating extensive datasets of neuronal information. Furthermore, MEAs capture extracellular field potentials from cultured cells, resulting in highly complex neuronal signals that necessitate precise spike sorting for meaningful data extraction. Nevertheless, conventional spike sorting methods face limitations in recognising diverse spike shapes, thereby constraining the full utilisation of the rich dataset acquired from MEA recordings. To overcome these limitations, we have developed a machine learning algorithm, named PseudoSort, which employs advanced self-supervised learning techniques, a distinctive density-based pseudo-labelling strategy, and an iterative fine-tuning process to enhance spike sorting accuracy. Through extensive benchmarking on large-scale simulated datasets, we demonstrate the superior performance of PseudoSort compared to recently developed machine learning-based (ML) spike sorting algorithms. We showcase the practical application of PseudoSort by utilising MEA recordings from hippocampal neurons exposed to subneuronal concentrations of monomeric Tau, a protein associated with Alzheimers disease (AD). Our results, validated against patch clamp experiments, unveil that monomeric Tau at subneuronal concentrations induces stimulation-dependent disruptions in both local and global activity of hippocampal neurons. Remarkably, patch clamp electrophysiology highlights the effect of combined Tau and neuronal stimulation treatment on excitatory postsynaptic currents, whereas PseudoSort excels in identifying neuronal clusters that exhibit diminished firing capacity following Tau treatment alone, i.e., in the absence of stimulation. This comprehensive approach validates the prowess of PseudoSort and unravels the intricate effects of Tau on neuronal activity, particularly in the context of AD.

neuroscience↗

bioRxiv2023

Lateral inhibition in V1 controls neural & perceptual contrast sensitivity

Lateral inhibition is a central principle for sensory system function. It is thought to operate by the activation of inhibitory neurons that restrict the spatial spread of sensory excitation. Much work on the role of inhibition in sensory systems has focused on visual cortex; however, the neurons, computations, and mechanisms underlying cortical lateral inhibition remain debated, and its importance for visual perception remains unknown. Here, we tested how lateral inhibition from PV or SST neurons in mouse primary visual cortex (V1) modulates neural and perceptual sensitivity to stimulus contrast. Lateral inhibition from PV neurons reduced neural and perceptual sensitivity to visual contrast in a uniform subtractive manner, whereas lateral inhibition from SST neurons more effectively changed the slope (or gain) of neural and perceptual contrast sensitivity. A neural circuit model identified spatially extensive lateral projections from SST neurons as the key factor, and we confirmed this with anatomy and direct subthreshold measurements of a larger spatial footprint for SST versus PV lateral inhibition. Together, these results define cell-type specific computational roles for lateral inhibition in V1, and establish their unique consequences on sensitivity to contrast, a fundamental aspect of the visual world.

neuroscience↗

bioRxiv2022

Narrowband gamma oscillations propagate and synchronize throughout the mouse thalamocortical visual system

Rhythmic oscillations of neural activity permeate sensory systems. Studies in the visual system propose that broadband gamma oscillations (30 - 80 Hz) facilitate neuronal communication underlying visual perception. However, broadband gamma oscillations within and across visual areas show widely varying frequency and phase, providing constraints for synchronizing spike timing. Here, we analyzed data from the Allen Brain Observatory and performed new experiments that show narrowband gamma (NBG) oscillations (50 - 70 Hz) propagate and synchronize throughout the awake mouse thalamocortical visual system. Lateral geniculate (LGN) neurons fired with millisecond precision relative to NBG phase in primary visual cortex (V1) and multiple higher visual areas (HVAs). NBG in HVAs depended upon retinotopically aligned V1 activity, and neurons that fired at NBG frequencies showed enhanced functional connectivity within and across visual areas. Remarkably, LGN ON versus OFF neurons showed distinct and reliable spike timing relative to NBG oscillation phase across LGN, V1, and HVAs. Taken together, NBG oscillations may serve as a novel substrate for precise coordination of spike timing in functionally distinct subnetworks of neurons spanning multiple brain areas during awake vision.

neuroscience↗

bioRxiv2021

Thalamic state controls timing and synchronization of primary somatosensory cortical representations in the awake mouse

The thalamus controls transmission of sensory signals from periphery to cortex, ultimately shaping perception. Despite this significant role, dynamic thalamic gating and the consequences for downstream cortical sensory representations have not been well studied in the awake brain. We optogenetically modulated the ventro-posterior medial thalamus in the vibrissa pathway of the awake mouse, and measured spiking activity in the thalamus, and activity in primary somatosensory cortex (S1) using extracellular electrophysiology and genetically encoded voltage imaging. Thalamic hyperpolarization significantly enhanced thalamic sensory-evoked bursting, yet surprisingly the S1 cortical response was not amplified, but instead timing precision was significantly increased, spatial activation more focused, and there was an increased synchronization of cortical inhibitory neurons. A thalamocortical network model implicates the modulation of precise timing of feedforward thalamic population spiking, presenting a highly sensitive, timing-based gating of sensory signaling to cortex.

neuroscience↗

bioRxiv2020

Spatial modulation of dark versus bright stimulus responses in mouse visual cortex

A fundamental task of the visual system is to respond to luminance increments and decrements. In primary visual cortex (V1) of cats and primates, luminance decrements elicit stronger, faster, and more salient neural activity (OFF responses) than luminance increments (ON responses). However, studies of V1 in ferrets and mice show that ON responses may be stronger. These discrepancies may arise from differences in species, experimental conditions, or from measuring responses in single neurons versus populations. Here, we examined OFF versus ON responses across different regions of visual space in both single neurons and populations of mouse V1. We used high-density silicon probes and whole-cell patch-clamp recordings to assess OFF versus ON dominance in local field potential (LFP), single neuron, and membrane potential responses. Across these levels, we found that OFF responses clearly dominated in the central visual field, whereas ON responses were more evident in the periphery. These observations were clearest in LFP and subthreshold membrane potential. Our findings consolidate and resolve prior conflicting results and reveal that retinotopy may provide a common organizing principle for spatially biasing OFF versus ON processing in mammalian visual systems.

neuroscience↗

bioRxiv2019

Diminished cortical excitation during perceptual impairments in a mouse model of autism

Sensory impairments are a core feature of autism spectrum disorder (ASD). These impairments affect visual perception (Robertson and Baron-Cohen, 2017), and have been hypothesized to arise from imbalances in cortical excitatory and inhibitory activity (Rubenstein and Merzenich, 2003; Nelson and Valakh, 2015; Sohal and Rubenstein, 2019); however, there is little direct evidence testing this hypothesis in identified excitatory and inhibitory neurons during impairments of sensory perception. Several recent studies have examined cortical activity in transgenic mouse models of ASD (Goel et al., 2018; Antoine et al., 2019; Lazaro et al., 2019), but have provided conflicting evidence for excitatory versus inhibitory activity deficits. Here, we utilized a genetically relevant mouse model of ASD (CNTNAP2-/- knockout, KO; Arking et al., 2008; Penagarikano et al., 2011) and directly recorded putative excitatory and inhibitory population spiking in primary visual cortex (V1) while measuring visual perceptual behavior (Speed et al., 2019). We found quantitative impairments in the speed, accuracy, and contrast sensitivity of visual perception in KO mice. These impairments were simultaneously associated with elevated inhibitory and diminished excitatory neuron activity evoked by visual stimuli during behavior, along with aberrant 3 - 10 Hz oscillations in superficial cortical layers 2/3 (L2/3). These results establish that perceptual deficits relevant for ASD can arise from diminished sensory activity of excitatory neurons in feedforward layers of cortical circuits.

neuroscience↗

bioRxiv2018

Cortical states control visual spatial perception

Many factors modulate the state of cortical activity, but the importance of cortical states for sensory perception remains debated. We trained mice to detect spatially localized visual stimuli, and simultaneously measured local field potentials and excitatory and inhibitory neuron populations across layers of primary visual cortex (V1). Cortical states with low firing rates and correlations between excitatory neurons, and reduced oscillatory activity in Layer 4, accurately predicted single trials of visual spatial detection behavior. Our results show that cortical states exert strong effects at the initial stage of cortical processing in V1, and play a decisive role for visual spatial behavior in mice.

neuroscience↗