Biology subjects

Arabzadeh, E.

Publications and source records attributed to Arabzadeh, E..

16 recordsLinked to original sources

bioRxiv2026

Cell-type specific inhibitory dynamics shape binocular response normalization in visual cortex

Response normalization during sensory processing is a canonical cortical computation thought to emerge from inhibition-stabilized networks (ISNs). A key prediction from ISNs is that inhibition tracks and scales with excitation, leading to sublinear response summation, but which interneuron classes mediate this operation is unclear. Here, we investigate temporal dynamics and response summation in parvalbumin (PV) and somatostatin (SST) interneurons in mouse binocular visual cortex (bV1). We find that both PV and SST interneurons are binocular but exhibit distinct temporal dynamics and summation profiles. Binocular responses in PV interneurons tracked pyramidal neuron responses, exhibiting sublinear summation consistent with ISN models. In contrast, binocular responses SST interneurons exhibited rapid temporal dynamics and linear or supralinear summation, deviating from ISN predictions. While both PV and SST neurons received excitatory drive via interhemispheric callosal input, they exhibited distinct cellular properties, synaptic dynamics and input-output transformations. Biophysically constrained simulations indicated that cellular and synaptic differences alone were insufficient to reproduce the observed response dynamics in vivo during binocular integration, which were better explained by class-specific differences in local inhibitory circuit motifs. Together, our results indicate that heterogeneous, cell-type-specific inhibitory dynamics shape response normalization in bV1, with PV but not SST interneurons having ISN-like properties.

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bioRxiv2026

Cortical TRPV1 modulates sensory processing through TRPA1-dependent mechanisms

Transient receptor potential vanilloid 1 (TRPV1) is classically recognised as a peripheral ion channel involved in nociception, but its physiological role in cortical sensory processing remains poorly understood. Here, we investigated whether cortical TRPV1 modulates tactile perception and sensory representations in the vibrissal primary somatosensory cortex (vS1) of mice. TRPV1 activation enhanced perceptual sensitivity, particularly for near-threshold tactile stimuli. In vS1, this was accompanied by stimulus-evoked responses that enhanced stimulus selectivity and discriminability. At the cellular level, activating TRPV1 increased excitability of pyramidal neurons in a TRPA1-dependent manner. Within vS1, TRPV1 activation reduced positive noise correlations and improved stimulus decoding through TRPA1-dependent changes in population activity. Together, these findings identify a TRPV1-TRPA1 signalling mechanism that regulates cortical gain, sharpens sensory representations and enhances perceptual sensitivity. Our results extend the established role of TRPV1 beyond peripheral sensory transduction to central sensory computation.

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bioRxiv2026

Superior Colliculus Neurons Encode and Causally Shape Sensory Decisions

The ability of an organism to attend to, and orient towards, relevant stimuli is critical for survival. In the mammalian brain, a principal brain region performing this function is the superior colliculus (SC). Despite its important role in attention and orienting movements, little is known about the role the SC plays in sensory decisions. Using Neuropixel recording and optogenetic perturbation of neuronal activity in awake behaving mice, we provide a quantitative link between the activity of neurons in the SC and the behavioural outcome during a whisker-dependent sensory detection task. Consistent with the idea that the SC contributes to sensory decision-making, the activity of SC neurons was correlated with behavioural performance. Furthermore, we found that optogenetic inhibition of the SC reduced behavioural performance without reducing sensitivity or reaction time. These findings indicate that the SC both encodes and causally shapes sensory decisions during a whisker-dependent task.

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bioRxiv2024

Diversity of ancestral brainstem noradrenergic neurons across species and multiple biological factors

The brainstem cell group, locus coeruleus (LC), is present across vertebrates and influences cardiorespiratory, metabolic, immune, and cognitive functions by activating in two putatively distinct firing patterns. Yet, the degree to which the LC firing rates and patterns are homogenous across species has never been assessed due to inherently limited sample sizes. To remedy this, we pooled cross-species data from 20 laboratories to show that firing rates differ across species and are modulated by sex, age, and type of in vitro or in vivo preparation. Contrary to the prevailing dual-mode firing pattern schema, we observed patterns spread across a low-dimensional manifold, with subregions enriched for specific biological factors and neurodegenerative disease models. Our findings show considerable diversity in an ancestral vertebrate neuromodulatory system.

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bioRxiv2023

Activation of M1 cholinergic receptors in mouse somatosensory cortex enhances information processing and improves detection behaviour

An important function of the brain is to form accurate representations of the world around us. To optimise sensory representations based on the demands of the environment, activity of cortical neurons is regulated by neuromodulators such as Acetylcholine (ACh). As such, ACh is implicated in cognitive functions including attention, arousal and sleep cycles. However, it is not clear how specific ACh receptors shape the baseline activity of cortical neurons and their evoked response to sensory stimuli. Here, we investigate the role of a densely expressed muscarinic ACh receptor 1 (M1) in information processing in the mouse primary somatosensory cortex (vS1) and in the animals sensitivity in detecting vibrotactile stimuli. We show that M1 activation significantly enhances the evoked response of vS1 neurons and the reversal of this enhancement by blocking M1. In addition, we demonstrate that M1 activation results in faster and more reliable neuronal responses, which is manifested by a significant reduction in response latencies and the trial-to-trial variability in neuronal activity. At the population level, M1 activation reduces the network synchrony and thus enhances the capacity of vS1 neurons in conveying sensory information. Consistent with the neuronal findings, we show that M1 activation significantly improves performances in a vibrotactile detection task. Overall, the M1-mediated enhancement in sensory efficiency reflects a multiplicative gain modulation at the neuronal level, resembling the changes observed during high attention states.

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bioRxiv2022

Visual awareness during the attentional blink is determined by representational similarity

Our visual perception seems effortless, but the brain has a limited processing capacity which curtails the amount of sensory information that can be brought into conscious awareness at any moment in time. A widely studied exemplar of this limitation is the attentional blink (AB), in which observers are unable to report the second of two rapidly sequential targets if it appears within 200-500 ms of the first. Despite the apparent ubiquity of the AB effect, its computational and neurophysiological underpinnings have remained elusive. Here we propose a simple computational model of temporal attention that unifies the AB with spatial and feature-based attention. We took a novel, integrative approach involving human psychophysics and functional brain imaging, along with neuronal recordings in mice to test this model. Specifically, we demonstrate that the AB only arises when visual targets have dissimilar representations in the brain but is absent when both targets have the same representation. Similarity in this context can be determined either by elementary features such as edge orientation, or by acquired, high-level factors such as numerical or alphabetical order. In this parsimonious model of the AB, attention to an initial target establishes a perceptual filter that is tuned to its unique representation in the brain. Subsequent items that match the filter remain available for conscious report, whereas those that do not match elude awareness altogether.

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bioRxiv2021

Sensory prediction errors increase coding efficiency in mouse visual cortex through gain amplification

The response of cortical neurons to sensory stimuli is shaped both by past events (adaptation) and the expectation of future events (prediction). Here we employed a visual stimulus paradigm with different levels of predictability to characterise how expectation influences orientation selectivity in the primary visual cortex (V1) of mice. We recorded neuronal activity using two-photon calcium imaging (GCaMP6f) while animals viewed sequences of grating stimuli which either varied randomly in their orientations or rotated predictably with occasional transitions to an unexpected orientation. For single neurons and the population, there was significant enhancement in the gain of orientation-selective responses to unexpected gratings. This gain-enhancement for unexpected stimuli was prominent in both awake and anaesthetised mice. We implemented a computational model to demonstrate how trial-to-trial variability in neuronal responses were best characterised when adaptation and expectation effects were combined.

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bioRxiv2020

State-dependent changes in perception and coding in the mouse somatosensory cortex

An animals behavioral state is reflected in the dynamics of cortical population activity and its capacity to process sensory information. To better understand the relationship between behavioral states and information processing, mice are trained to detect varying amplitudes of whisker-deflection under two-photon calcium imaging. Layer 2/3 neurons (n=1436) in the vibrissal primary somatosensory cortex are imaged across different behavioral states, defined based on detection performance (low to high-state) and pupil diameter. The neurometric curve in each behavioral state mirrors the corresponding psychometric performance, with calcium signals predictive of the animals choice outcome. High behavioral states are associated with lower network synchrony, extending over shorter cortical distances. The decrease of correlations in variability across neurons in the high state results in enhanced information transmission capacity at the population level. The observed state-dependent changes suggest that the coding regime within the first stage of cortical processing may underlie adaptive routing of relevant information through the sensorimotor system. HighlightsO_LINetwork synchrony and pupil diameter are coupled to changes in behavioral state. C_LIO_LIHigh behavioral state results in enhanced information transmission capacity at the population level, with neurometric curve in each behavioral state mirroring the corresponding psychometric performance C_LIO_LIBehavioral state and calcium signal in primary somatosensory cortex predict choice outcome. C_LI eTOCO_ST_ABSIn BriefC_ST_ABSLee et al. investigates the relationship between behavioral states and information processing in the primary somatosensory cortex. They demonstrate increases in behavioral state results in decrease cortical variability, enhanced information transmission capacity and stimulus encoding at the population level.

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bioRxiv2020

Neural Network Poisson Models for Behavioural and Neural Spike Train Data

AO_SCPLOWBSTRACTC_SCPLOWOne of the most important and challenging application areas for complex machine learning methods is to predict, characterize and model rich, multi-dimensional, neural data. Recent advances in neural recording techniques have made it possible to monitor the activities of a large number of neurons across different brain regions as animals perform behavioural tasks. This poses the critical challenge of establishing links between neural activity at a microscopic scale, which might for instance represent sensory input, and at a macroscopic scale, which then generates behaviour. Predominant modeling methods apply rather disjoint techniques to these scales; by contrast, we suggest an end-to-end model which exploits recent developments of flexible, but tractable, neural network point-process models to characterize dependencies between stimuli, actions, and neural data. We apply this model to a public dataset collected using Neuropixel probes in mice performing a visually-guided behavioural task as well as a synthetic dataset produced from a hierarchical network model with reciprocally connected sensory and integration circuits intended to characterize animal behaviour in a fixed-duration motion discrimination task. We show that our model outperforms previous approaches and contributes novel insights into the relationships between neural activities and behaviour.

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bioRxiv2020

Loss of the Er81 Transcription Factor in Cholinergic Cells Alters Striatal Activity and Habit Formation

The finely-tuned activity of cholinergic interneurons (CINs) in the striatum is key for motor control, learning, and habit formation. Yet, the molecular mechanisms that determine their unique functional properties remain poorly explored. Using a combination of genetic and biochemical assays, in vitro and in vivo physiological characterisation, we report that selective ablation of the Er81 transcription factor leads to prominent changes in CIN molecular, morphological and electrophysiological features. In particular, the lack of Er81 amplifies intrinsic delayed-rectifier and hyperpolarization-activated currents, which subsequently alters the tonic and phasic activity of CINs. We further demonstrate that these alterations enhance their pause and time-locked responses to sensorimotor inputs in awake mice. Finally, this study reveals an Er81-dependent developmental mechanism in CINs essential for habit formation in adult mice. Highlights- The Er81 transcription factor is expressed in striatal cholinergic interneurons (CINs) - Conditional deletion of Er81 alters key molecular, morphological and electrophysiological properties of CINs in adult mice - Deletion of Er81 reduces the intrinsic excitability of CINs by upregulating delayed rectifier and hyperpolarization-activated currents - Deletion of Er81 alters in vivo striatal activity and habit formation

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bioRxiv2019

Enhanced sensory coding in mouse vibrissal and visual cortex through TRPA1

Transient Receptor Potential Ankyrin 1 (TRPA1) is a non-selective cation channel, which is broadly expressed throughout the body. Despite its expression in the mammalian cortex, little is known about the contribution of TRPA1 to cortical function. Here we investigate the role of TRPA1 in sensory information processing by performing electrophysiological recording and 2-photon calcium imaging from two sensory areas in mice: the primary vibrissal somatosensory cortex (vS1) and the primary visual cortex (V1). In vS1, local activation of TRPA1 by its agonist AITC significantly increased the spontaneous activity of cortical neurons, their evoked response to vibrissal stimulation, and their response range, consistent with a positive gain modulation. TRPA1 inhibition with HC-030031 reversed these modulations to below initial control gains. The gain modulations were absent in TRPA1 Knockout mice. In V1, TRPA1 activation increased the gain of direction and orientation selectivity similarly to the gain modulations observed in vS1 cortex. Linear decoding analysis of V1 population activity confirmed faster and more reliable encoding of visual signals in the presence of TRPA1 activation. Overall, our findings reveal a physiological role for TRPA1 in enhancing sensory signals in the mammalian cortex.

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bioRxiv2019

Superior colliculus modulates cortical coding of somatosensory information

The cortex sends a direct projection to the superior colliculus. What is largely unknown is whether (and if so how) the superior colliculus modulates activity in the cortex. Here, we directly investigate this issue, showing that optogenetic activation of superior colliculus changes the input-output relationship of neurons in somatosensory cortex during whisker movement, enhancing responses to low amplitude whisker deflections. While there is no direct pathway from superior colliculus to somatosensory cortex, we found that activation of superior colliculus drives spiking in the posterior medial (POm) nucleus of the thalamus via a powerful monosynaptic pathway. Furthermore, POm neurons receiving input from superior colliculus provide excitatory input to somatosensory cortex. Silencing POm abolished the capacity of superior colliculus to modulate cortical whisker responses. Our findings indicate that the superior colliculus, which plays a key role in attention, modulates sensory processing in somatosensory cortex via a powerful disynaptic pathway through the thalamus.

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bioRxiv2019

Neural dynamics of the attentional blink revealed by encoding orientation selectivity during rapid visual presentation

The human brain is inherently limited in the information it can make consciously accessible. When people monitor a rapid stream of visual items for two targets, they can typically report the first, but not the second target, if these appear within 200-500 ms of each other, a phenomenon known as the attentional blink (AB). No work has determined the neural basis for the AB, partly because conventional neuroimaging approaches lack the temporal resolution to adequately characterise the neural activity elicited by each item in a rapid stream. Here we introduce a new approach that can identify the precise effect of the AB on behaviour and neural activity. Specifically, we employed a multivariate encoding approach to extract feature-selective information carried by randomly-oriented gratings within a rapid serial stream. We show that feature selectivity is enhanced for correctly reported targets and suppressed when the same items are missed. By contrast, no such effects were apparent for irrelevant distractor items. Our findings point to a new theoretical account that involves both short- and long-range temporal interactions between visual items competing for consciousness.

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bioRxiv2019

Forward modelling reveals dynamics of neural orientation tuning to unconscious visual stimuli during binocular rivalry

When different visual stimuli are presented to the two eyes, they typically compete for access to conscious perception, a phenomenon known as binocular rivalry. Previous studies of binocular rivalry have shown that neural responses to consciously suppressed stimuli are markedly diminished in magnitude, though they may still be encoded to some extent. Here we employed multivariate forward modelling of human electroencephalography (EEG) data to quantify orientation-selective responses to visual gratings during binocular rivalry. We found robust orientation tuning to both conscious and unconscious gratings. This tuning was enhanced for the suppressed stimulus well before it was available for conscious report. The same pattern was evident in the overall magnitude of neural responses, and it emerged even earlier than the changes in neural tuning. Taken together, our findings suggest that rivalry suppression affects broadband, non-orientation selective aspects of neural activity before refining fine-grained feature-selective information.

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bioRxiv2018

Diverse tuning underlies sparse activity in L2/3 vibrissal cortex of awake mice

It is widely reported that superficial layers of the somatosensory cortex exhibit sparse firing. This sparseness could reflect weak feedforward sensory inputs that are not sufficient to generate action potentials in these layers. Alternatively, sparseness might reflect tuning to unknown or higher-level complex features that are not fully explored in the stimulus space. Here, we examined these hypotheses by applying a range of vibrotactile and manual vibrissal stimuli in awake, head-fixed mice while performing loose-seal cell-attached recordings from the vibrissal primary somatosensory (vS1) cortex. A high-velocity stimulus delivered by a piezo-electric actuator evoked activity in a small fraction of regular spiking supragranular neurons (29%) in awake condition. However, a majority of the supragranular regular spiking neurons (84%) were driven by manual stimulation of whiskers. Our results suggest that most neurons in the superficial layers of vS1 cortex contribute to coding in awake conditions when neurons may encounter their preferred feature(s) during whisker-object interactions.

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bioRxiv2017

Prediction Error and Repetition Suppression Have Distinct Effects on Neural Representations of Visual Information

Predictive coding theories argue that recent experience establishes expectations in the brain that generate prediction errors when violated. Prediction errors provide a possible explanation for repetition suppression, where evoked neural activity is attenuated across repeated presentations of the same stimulus. The predictive coding account argues repetition suppression arises because repeated stimuli are expected, whereas non-repeated stimuli are unexpected and thus elicit larger neural responses. Here we employed electroencephalography in humans to test the predictive coding account of repetition suppression by presenting sequences of visual gratings with orientations that were expected either to repeat or change in separate blocks of trials. We applied multivariate forward modelling to determine how orientation selectivity was affected by repetition and prediction. Unexpected stimuli were associated with significantly enhanced orientation selectivity, whereas selectivity was unaffected for repeated stimuli. Our results suggest that repetition suppression and expectation have separable effects on neural representations of visual feature information.

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