Biology subjects

Mohajerani, M.

Publications and source records attributed to Mohajerani, M..

16 recordsLinked to original sources

bioRxiv2026

Refinement and Retrospective Shift of the CA1 Place Code during Food-Carrying Decisions

Food carrying is an adaptive component of foraging that integrates resource evaluation with home-directed navigation, providing a naturalistic model for investigating how the brain organizes goal-directed behaviour. Despite extensive work on hippocampal coding during navigation and homing, how CA1 representations are reorganized when animals spontaneously transport acquired food home remains largely unexplored. We recorded dorsal CA1 population activity using one-photon calcium imaging with a V4 Miniscope while mice performed a self-paced foraging task in which food could be consumed at the acquisition site followed by a homeward return or carried to the home for consumption. Mice preferentially carried larger pellets, indicating that transport behaviour was sensitive to resource value. CA1 spatial coding differed systematically across behavioural outcomes. During carry-homeward runs, spatial representations were sparser, conveyed more spatial information, and showed greater trial-to-trial stability than during eat-inward runs, indicating a more precise and reliable place code during home-directed transport. Place fields also shifted forward during carrying, consistent with a retrospective bias toward recently traversed locations. By linking a self-generated food-handling decision to coordinated changes in the precision, stability, and temporal organization of CA1 activity, these findings extend hippocampal spatial-coding frameworks from trained navigation to ecologically grounded foraging behaviour.

neuroscience↗

bioRxiv2025

Vision and touch used for catching small balls with a power grip and large balls with a precision grip supports dual visuomotor channel theory

The dual visuomotor channel theory of grasping posits that distinct neural pathways mediate hand shaping in response to a targets extrinsic (e.g., location) and intrinsic (e.g., size and shape) properties. To evaluate this theory, we examined grasp behavior in human participants as they caught balls of four diameters (2.5-9 cm) thrown toward them. Hand shaping during catching was compared with that observed during the pickup of stationary balls and the interception of rolling balls. Kinematic measures included digit opposition distance (thumb pad to index finger pad) and prehension span (digit pad to palm distance), obtained using electromagnetic sensors, 3D video capture, and frame-by-frame video analysis. Participants displayed significantly greater hand opening when catching thrown balls than when interacting with static or rolling balls. Nonetheless, the maximum pregrasp aperture (MPA), contact grasp aperture (CGA), and terminal grasp aperture (TGA) scaled proportionally with ball size across all conditions. Ball size further influenced grasp type: small thrown balls were caught with power grips, while larger balls were caught with precision grips. In contrast, precision grips were used consistently when picking up stationary balls or grasping intercepting rolling ones. In the catching condition, grasp type and the trajectory of digit closure were also affected by the location of ball to hand contact. These findings support the dual visuomotor channel theory by demonstrating that anticipatory hand opening reflects target location, whereas grip selection reflects target size. Moreover, the modulation of grasp type and digit closure by tactile contact suggests that somatosensory input may operate within a dual-channel framework analogous to that of vision.

neuroscience↗

bioRxiv2023

A Spatio-temporal Investigation of Dynamics of a Two-dimensional Multi-scale Fitz-Hugh Nagumo Neuronal Network

The multi scale architecture by Breakspear and Stam [2] introduces a framework to consider the dynamical processes specific to a nested hierarchy of spatial scales, from neuronal masses to cortical columns and functional brain regions. They hypothesize that the neural dynamics is a function of the structural properties of the neural system at a certain scale as well as the emergent behaviour of the smaller scale activities. In this paper, we adopt the multi scale framework to investigate a generalized version of the stochastic Fitz-Hugh Nagumo (FHN) neuronal system within the small scale process and their emergent large scale synchronization effects leading to the formation of travelling waves in the large scale system. We extend the multi scale framework to incorporate the nonlinear biological synaptic connectivity at the neuronal mass scale. The modified multi scale scheme utilizes the two-dimensional wavelet decomposition in the plane of dynamical interconnected neurons. In addition, we consider the large-scale spatio-temporal system of FHN reaction-diffusion partial differential equations and evaluate the formation of travelling waves in the simplified context of a cellular neural network (CNN) model. Numerical examples are given to illustrate the response and the isolated influence of the strength of neural connectivity on the travelling wave formation modes.

neuroscience↗

bioRxiv2023

Information-theory analysis of mouse string-pulling agrees with Fitts's Law: Increasing task difficulty engages multiple sensorimotor modalities in a dual oscillator behavior

Mouse string pulling, in which a mouse reels in a string with hand-over-hand movements, can provide insights into skilled motor behavior, neurological status, and cognitive function. The task involves two oscillatory movements connected by the string. The snout tracks the pendulum movement of the string produced by hand-over-hand pulls and so guides the hands to grasp the string. The present study examines the allocation of time required to pull strings of varying diameter. Movement is also described with end-point measures, string-pulling topography with 2D markerless pose estimates based on transfer learning with deep neural networks, and Mat-lab image-segmentation and heuristic algorithms for object tracking. With reduced string diameter, mice took longer to pull 60cm long strings. They also made more pulling cycles, misses, and mouth engagements, and displayed changes in the amplitude and frequency of pull cycles. The time measures agree with Fittss law in showing that increased task difficulty slows behavior and engages multiple compensatory sensorimotor modalities. The analysis reveals that time is a valuable resource in skilled motor behavior and information-theory can serve as a measure of its effective use.

animal behavior and cognition↗

bioRxiv2022

Hippocampal ripples coincide with ''up-state'' and cortical spindles in Retrosplenial Cortex

During NREM sleep hippocampal Sharp-wave ripples (SWR) events are thought to stabilize memory traces for long-term storage in downstream neocortical structures. Within the neocortex, Default Mode Network (DMN) areas interact preferentially with the hippocampus purportedly to consolidate those traces. Transient bouts of slow oscillations and sleep spindles in DMN areas are often observed around SWRs, suggesting that these two activities are related and that their interplay possibly contributes to memory consolidation. To investigate how SWRs interact with the DMN and spindles, we combined cortical wide-field voltage imaging, ECoG, and hippocampal LFP recordings in anesthetized and sleeping mice. Here we show that, during SWR, "up-states" and spindles reliably co-occur in a cortical subnetwork centered around the Retrosplenial cortex. Furthermore, Retrosplenial transient activations and spindles predict Slow Gamma oscillations in CA1 during SWRs. Together, our results suggest that Retrosplenial-hippocampal interaction may be a central source of information exchange between cortex and hippocampus.

neuroscience↗

bioRxiv2022

Functional organization of mouse auditory cortex in response to stimulus complexity and brain state

The functional organization of sensory cortices is modulated by both extrinsic events and intrinsic states. The present study aimed to assess the mouse auditory cortex (AC) responses under varying conditions of stimulus complexity and brain state. Using wide-field calcium imaging, our results suggest a complete outline of topographic maps of frequency and FM rate as well as highly responsive regions to mouse ultrasonic vocalizations (USVs) in both awake and anesthetized states. Three new regions responsive to high-frequency tones and four new gradients responsive to frequency modulations (FMs) were identified. These maps are highly replicable across weeks and between animals. In awake versus anesthetized states, cortical responsiveness to pure tones was stronger, and regions that preferentially responded to slow rate FMs were smaller. In both states, fast FM regions showed the greatest contribution to the processing of USVs. Finally, our modeling of how best tone frequency or FM rate changes as a function of distance along a topographic gradient resulted in a sigmoid function. Together, our findings provide a better understanding of mouse AC functional organization and how this organization is modulated by changes in stimulus complexity and brain state. The function of newly identified regions in higher-order auditory/vocal processing and animal behavior should be considered in future research.

neuroscience↗

bioRxiv2022

Tactile Stimulation Improves Cognition, Motor, and Anxiety-Like Behaviours and Attenuates the AD Pathology in Adult APP NL-G-F/NL-G-F mice

Alzheimers Disease (AD) is one of the largest health crises in the world. There are, however, limited but expensive pharmaceutical interventions to treat AD and most of the treatment options are not for cure or prevention, but to slow down the progression of the disease. The aim of this study was to examine the effect of tactile stimulation on AD-like symptoms and pathology in APP NL-G-F/NL-G-F mice, a mouse model of AD. The results show that tactile stimulation improves the AD-like symptoms on tests of cognition, motor, and anxiety-like behaviours and these improvements are associated with reduced AD pathology in APP mice.

neuroscience↗

bioRxiv2022

Early Tactile Stimulation Influences the Development of Alzheimer Disease in Gestationally Stressed APPNL-G-F/ NL-G-F Adult mice

Alzheimer Disease (AD) is associated with cerebral plaques and tangles, reduced synapse number, and shrinkage in several brain areas and these morphological effects are associated with the onset of compromised cognitive, motor, and anxiety-like behaviours. The focus of this study was to examine the effect of neonatal tactile stimulation on AD-like behavioural and neurological symptoms on APP NL-G-F/NL-G-F mice, a mouse model of AD. Our findings indicate that neonatal tactile stimulation improves cognition, motor skills, and anxiety-like symptoms in both gestationally stressed and non-stressed adult APP mice and that these alterations are associated with reduced A{beta} plaque formation. Thus, tactile stimulation appears to be a promising non-invasive preventative strategy for slowing the onset of dementia in aging animals.

neuroscience↗

bioRxiv2021

NERD-seq: A novel approach of Nanopore direct RNA sequencing that expands representation of non-coding RNAs

The new next-generation sequencing platforms by Oxford Nanopore Technologies for direct RNA sequencing (direct RNA-seq) allow for an in-depth and comprehensive study of the epitranscriptome by enabling direct base calling of RNA modifications. Non-coding RNAs constitute the most frequently documented targets for RNA modifications. However, the current standard direct RNA-seq approach is unable to detect many of these RNAs. Here we present NERD-seq, a sequencing approach which enables the detection of multiple classes of non-coding RNAs excluded by the current standard approach. Using total RNA from a tissue with high known transcriptional and non-coding RNA activity in mouse, the brain hippocampus, we show that, in addition to detecting polyadenylated coding and non-coding transcripts as the standard approach does, NERD-seq is able to significantly expand the representation for other classes of RNAs such as snoRNAs, snRNAs, scRNAs, srpRNAs, tRNAs, rRFs and non-coding RNAs originating from LINE L1 elements. Thus, NERD-seq presents a new comprehensive direct RNA-seq approach for the study of epitranscriptomes in brain tissues and beyond.

genomics↗

bioRxiv2020

Increased processing of SINE B2 non coding RNAs unveils a novel type of transcriptome de-regulation underlying amyloid beta neuro-pathology

More than 97% of the mammalian genome is non-protein coding, and repetitive elements account for more than 50% of noncoding space. However, the functional importance of many non-coding RNAs generated by these elements and their connection with pathologic processes remains elusive. We have previously shown that B2 RNAs, a class of non-coding RNAs that belong to the B2 family of SINE repeats, mediate the transcriptional activation of stress response genes (SRGs) upon application of a stimulus. Notably, B2 RNAs bind RNA Polymerase II (RNA Pol II) and suppress SRG transcription during pro-stimulation state. Upon application of a stimulus, B2 RNAs are processed into fragments and degraded, which in turn releases RNA Pol II from suppression and upregulates SRGs. Here, we demonstrate a novel role for B2 RNAs in transcriptome response to amyloid beta toxicity and pathology in the mouse hippocampus. In healthy hippocampi, activation of SRGs is followed by a transient upregulation of pro-apoptotic factors, such as p53 and miRNA-34c, which target SRGs creating a negative feedback loop that facilitates transition to the pro-stimulation state. Using an integrative RNA genomics approach, we show that in mouse hippocampi of an amyloid precursor protein knock-in mouse model and in an in vitro cell culture model of amyloid beta toxicity, this regulatory loop is dysfunctional due to increased levels of B2 RNA processing, constitutively elevated SRG expression and high p53 levels. Evidence indicates that Hsf1, a master regulator of stress response, mediates B2 RNA processing in cells, and is upregulated during amyloid toxicity accelerating the processing of SINE RNAs and SRG hyper-activation. Our study reveals that in mouse, SINE RNAs constitute a novel pathway deregulated in amyloid beta pathology, with potential implications for similar cases in the human brain, such as Alzheimers disease (AD). This data attributes a role to SINE RNA processing in a pathological process as well as a new function to Hsf1 that is independent of its transcription factor activity.

genomics↗

bioRxiv2020

Cholinergic upregulation by optogenetic stimulation of nucleus basalis after photothrombotic stroke in forelimb somatosensory cortex improves endpoint and motor but not sensory control of skilled reaching in mice

A network of cholinergic neurons in the basal forebrain innerve the forebrain and are proposed to contribute to a variety of functions including attention, and cortical plasticity. This study examined the contribution of the nucleus basalis cholinergic projection to the sensorimotor cortex on recovery on a skilled reach-to-eat task following photothrombotic stroke in the forelimb region of the somatosensory cortex. Mice were trained to perform a single-pellet skilled reaching task and their pre and poststroke performance, from Day 4 to Day 28 poststroke, was assessed frame-by-frame by video analysis with end point, movement and sensorimotor integration measures. Somatosensory forelimb lesions produced impairments in endpoint and movement component measures of reaching and increased the incidence of fictive eating, a sensory impairment in mistaking a missed reach for a successful reach. Upregulated acetylcholine (ACh) release, as measured by local field potential recording, elicited via optogenetic stimulation of the nucleus basalis improved recovery of reaching and improved movement scores but did not affect a sensorimotor integration impairment poststroke. The results show that the mouse cortical forelimb somatosensory region contributes to forelimb motor behavior and suggest that ACh upregulation could serve as an adjunct to behavioral therapy for the acute treatment of stroke.

neuroscience↗

bioRxiv2020

Miniaturized head-mounted device for whole cortex mesoscale imaging in freely behaving mice

The advent of genetically encoded calcium indicators, along with surgical preparations such as thinned skulls or refractive index matched skulls, have enabled mesoscale cortical activity imaging in head-fixed mice. Such imaging studies have revealed complex patterns of coordinated activity across the cortex during spontaneous behaviors, goal-directed behavior, locomotion, motor learning, and perceptual decision making. However, neural activity during unrestrained behavior significantly differs from neural activity in head-fixed animals. Whole-cortex imaging in freely behaving mice will enable the study of neural activity in a larger, more complex repertoire of behaviors not possible in head-fixed animals. Here we present the "Mesoscope," a wide-field miniaturized, head-mounted fluorescence microscope compatible with transparent polymer skulls recently developed by our group. With a field of view of 8 mm x 10 mm and weighing less than 4 g, the Mesoscope can image most of the mouse dorsal cortex with resolution ranging from 39 to 56 {micro}m. Stroboscopic illumination with blue and green LEDs allows for the measurement of both fluorescence changes due to calcium activity and reflectance signals to capture hemodynamic changes. We have used the Mesoscope to successfully record mesoscale calcium activity across the dorsal cortex during sensory-evoked stimuli, open field behaviors, and social interactions. Finally, combining the mesoscale imaging with electrophysiology enabled us to measure dynamics in extracellular glutamate release in the cortex during the transition from wakefulness to natural sleep.

neuroscience↗

bioRxiv2019

A toolbox for automated video analysis of rodents engaged in string-pulling: Phenotyping motor behavior of mice for sensory, whole-body and bimanual skilled hand function

String-pulling in rodents (rats and mice) is a task in which animals make hand-over-hand movements to spontaneously reel in a string with or without a food reward attached to its end. The task elicits bilateral skilled hand movements for which rodents require little training. The task is suitable for phenotyping physiology and pathophysiology of sensorimotor integration in rodent models of neurological and motor disorders. Because a rodent stands in the same location and its movements are repetitive, the task lends itself to quantification of topographical and kinematic parameters for on-line tactile tracking of the string, skilled hand movements for grasping, and rhythmical bilateral forearm movements to advance the string. Here we describe a Matlab(R) based software with a graphical user interface to assist researchers in analyzing the video record of string pulling. The software allows global characterization of position and motion using optical flow estimation, descriptive statistics, principal component, and independent component analyses as well as temporal measures of Fano factor, entropy, and Higuchi fractal dimension. Based on image segmentation and object tracking heuristic algorithms, the software also allows independent tracking of the body, ears, nose, and forehands for estimation of kinematic parameters such as body length, body angle, head roll, head yaw, head pitch, movement paths and speed of hand movement. The utility of the task and that of the software is presented by describing mouse strain characteristics in string-pulling behavior of two strains of mice, C57BL/6 and Swiss Webster. Postural and skilled hand kinematic differences that characterize the strains highlight the utility of the task and assessment methods for phenotypic and neurological analysis of healthy and rodent models of diseases such as Parkinsons, Huntingtons, Alzheimers and other neurological and motor disorders. Significance statementMouse models are used to investigate the physiology and pathophysiology of motor deficits observed in human neurological conditions, for testing substances for therapeutic drug development, and to investigate the role of neural systems and their genetic basis in the expression of behavior. Behavioral tasks involving unconditioned and natural behavior can provide rich insights into motor performance in animal models and analyses can be aided by the automated processing of video data for reliable quantification and high throughput.

neuroscience↗

bioRxiv2018

Low-Cost Solution for Rodent Home-Cage Behaviour Monitoring

In the current research on measuring complex behaviours/phenotyping in rodents, most of the experimental design requires the experimenter to remove the animal from its home-cage environment and place it in an unfamiliar apparatus (novel environment). This interaction may influence behaviour, general well-being, and the metabolism of the animal, affecting the phenotypic outcome even if the data collection method is automated. Most of the commercially available solutions for home-cage monitoring are expensive and usually lack the flexibility to be incorporated with existing home-cages. Here we present a low-cost solution for monitoring home-cage behaviour of rodents that can be easily incorporated to practically any available rodent home-cage. To demonstrate the use of our system, we reliably predict the sleep/wake state of mice in their home-cage using only video. We validate these results using hippocampal local field potential (LFP) and electromyography (EMG) data. Our approach provides a low-cost flexible methodology for high-throughput studies of sleep, circadian rhythm and rodent behaviour with minimal experimenter interference.

animal behavior and cognition↗

bioRxiv2017

New waves: Rhythmic electrical field stimulation systematically alters spontaneous slow dynamics across mouse neocortex

The signature rhythm of slow-wave forebrain activity is the large amplitude, slow oscillation (SO: ~1 Hz) made up of alternating synchronous periods of depolarizing and hyperpolarizing states at the single cell and network levels. On each wave, the SO originates at a unique location and propagates across the neocortex. Attempts to manipulate SO activity using electrical fields have been shown to entrain cortical networks and enhance memory performance. However, neural activity during this manipulation has remained elusive due to methodological issues in typical electrical recordings. Here we use voltage-sensitive dye (VSD) imaging in a bilateral cortical preparation of urethane-anesthetized mice to track SO cortical activity and its modulation by sinusoidal electrical field stimulation applied to frontal regions. We show that under spontaneous conditions, the SO propagates in two main opposing directional patterns along an anterior lateral - posterior medial axis. Rhythmic field stimulation alters spontaneous propagation to reflect activity that repeats cycle after cycle with distributed and varied anterior initiation zones and a consistent termination zone in the posterior somatosensory cortex. Our results show that slow electrical field stimulation stereotypes ongoing slow cortical dynamics during sleep-like states.\n\nAuthor ContributionsA.G., J.K.A., M.H.M. and C.T.D. designed the study. A.G. and J.K.A. performed the experiments. A.G. analyzed the data. A.G. wrote the manuscript, which all authors commented on and edited. C.T.D. and M.H.M. supervised the study.

neuroscience↗

bioRxiv2016

Optical-flow analysis toolbox for characterization of spatiotemporal dynamics in mesoscale optical imaging of brain activity

Wide-field optical imaging techniques constitute powerful tools to sample and study mesoscale neuronal activity. The sampled data constitutes a sequence of image frames in which one can perceive the flow of brain activity starting and terminating at source and sink locations respectively. The most common data analyses include qualitative assessment to identify sources and sinks of activity as well as their trajectories. The quantitative analyses is mostly based on computing the temporal variation of the intensity of pixels while a few studies have also reported estimates of wave motion using optical-flow techniques from computer vision. A comprehensive toolbox for the quantitative analyses of mesoscale brain activity data however is still missing. We present a graphical-user-interface based Matlab(R) toolbox for investigating the spatiotemporal dynamics of mesoscale brain activity using optical-flow analyses. The toolbox includes the implementation of three optical-flow methods namely Horn-Schunck, Combined Local-Global, and Temporospatial algorithms for estimating velocity vector fields of perceived flow in mesoscale brain activity. From the velocity vector fields we determine the locations of sources and sinks as well as the trajectories and temporal velocities of activity flow. Using our toolbox, we compare the efficacy of the three optical-flow methods for determining spatiotemporal dynamics by using simulated data. We also demonstrate the application of optical-flow methods onto sensory-evoked calcium and voltage imaging data. Our results indicate that the combined local-global method we employ, yields results that correlate with the manual assessment. The automated approach permits rapid and effective quantification of mesoscale brain dynamics and may facilitate the study of brain function in response to new experiences or pathology.\n\nConflicts of Interestnone\n\nAuthor contribution statementMHM, MM, NV, and SI designed the study. NA and SI wrote Matlab(R) code for the toolbox and designed the simulated data. MHM, and NA performed the experiments. NA and SI analyzed the data. SI, NA, and MHM wrote the manuscript.

neuroscience↗