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Kheradpezhouh, E.

Publications and source records attributed to Kheradpezhouh, E..

6 recordsLinked to original sources

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.

neuroscience↗

Integrated transcriptomics and proteomics define the TRP channel hierarchy in mouse cortex

Transient receptor potential (TRP) channels are evolutionarily conserved polymodal cation channels that mediate diverse sensory functions across the animal kingdom. Although TRP channels play key roles in peripheral sensation, their expression and functional relevance in the cerebral cortex remain poorly defined. Here, we integrate long- and short-read transcriptomics, targeted qPCR and membrane-aware proteomics to quantify TRP family members in adult mouse cortex. Across transcriptomic platforms, cortical TRP expression is dominated by TRPML, TRPC, and TRPM subfamilies, with lower representation of TRPP/TRPV, whereas Trpa1 and Trpv1 lie near empirical detection thresholds. Our proteomic workflow yields reproducible protein-level evidence for a subset of cortical TRPs, including TRPV2, TRPC4, TRPM3, TRPM7 and TRPP2, consistent with transcript rank order, while TRPA1/TRPV1 do not meet replicate-level protein-group detection criteria under 1% FDR control. Together, these multi-platform measurements establish a quantitative reference for cortical TRP biology and a framework for profiling low-abundance ion channels in complex brain tissue.

molecular biology↗

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.

neuroscience↗

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.

neuroscience↗

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.

neuroscience↗

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.

neuroscience↗