Biology subjects

Dominiak, S.

Publications and source records attributed to Dominiak, S..

5 recordsLinked to original sources

bioRxiv2025

Locomotion Selectively Amplifies Sensitizing Neurons in Primary Visual Cortex

Sensory processing in the cortex reflects both adaptation to external stimuli and changes in internal state. To investigate how these processes interact in layer 2/3 of mouse V1 we combined calcium imaging, optogenetics and circuit modelling. We find that locomotion preferentially increases the responses of pyramidal cells (PCs) that sensitize during visual stimulation compared to those that depress. A model explains this differential modulation through: (i) variations in the strength of PV and SST connectivity to individual PCs, (ii) broad locomotion-dependent weakening of PC and PV synapses, and (iii) reduced SST inhibition targeting sensitizing PCs. Differences in PV:SST input ratios across sensitizing and depressing PCs can be reproduced by a random-connectivity model based on measured interneuron densities, connection probabilities and synaptic strengths. Thus, stochastic variation in local inhibitory connectivity can explain much of the functional heterogeneity across PCs, while state-dependent modulation of inhibitory synapses reorganizes this balance during locomotion to bias cortical population activity towards sensitizing dynamics. The apparently paradoxical combination of increased PC response but decreased synaptic strength is consistent with a state-dependent gating mechanism that boosts signals leaving V1 while simultaneously preventing disruption of the local excitatory-inhibitory balance required for stable computation.

neuroscience↗

bioRxiv2024

Random connectivity generates inhibitory microcircuits that decorrelate adaptation in visual cortex

Inhibitory neurons are fundamental to sensory processing in the cortex but the rules governing their connections with excitatory neurons are unclear. Are pyramidal cells with different functions generated through specific or random connections? We used two-photon imaging, optogenetics and modelling to investigate opposing forms of adaptation in layer 2/3 of mouse visual cortex. We find that a slow modulatory drive acts differentially depending on the relative strength of inputs that individual pyramidal cells receive from parvalbumin-positive and somatostatin-positive interneurons. The number of depressing and sensitizing pyramidal cells could be explained quantitatively by the simplest connectivity rule - all inhbitory synapses made randomly. The functional heterogeneity of the pyramidal cell population therefore begins with general statistics of the connectome - interneurons are much sparser and connect with probabilities far less than one. The resulting "patchwork" of inhibitory microcircuits causes modulatory inputs to strongly decorrelate pyramidal cells on the behavioural time-scale of seconds.

neuroscience↗

bioRxiv2023

Refined movement analysis in the Staircase test reveals differential motor deficits in mouse models of stroke

Accurate assessment of post-stroke deficits is vital in translational research. Recent advances in machine learning provide unprecedented precision in quantifying rodent motor behavior post-stroke. However, the extent to which these tools can detect lesion-specific upper extremity deficits remains unclear. Using proximal middle cerebral artery occlusion (MCAO) and cortical photothrombosis (PT), we assessed post-stroke impairments in mice through the Staircase test. Lesion locations were identified using 7T-MRI. Machine learning was applied to reconstruct kinematic trajectories using MouseReach, a data-processing toolbox. This yielded 30 refined outcome parameters effectively capturing motor deficits. Lesion reconstructions located ischemic centers in the striatum (MCAO) and sensorimotor cortex (PT). Pellet retrieval was altered in both cases but did not correlate with stroke volume or ischemia extent. Instead, cortical ischemia was characterized by increased hand slips and modified reaching success. Striatal ischemia led to progressively prolonged reach durations, mirroring delayed symptom onset in basal ganglia strokes. In summary, refined machine learning-based movement analysis revealed specific deficits in mice after cortical and striatal ischemia. These findings emphasize the importance of thorough behavioral profiling in preclinical stroke research to increase translational validity of behavioral assessments.

neuroscience↗

bioRxiv2022

What moves when mice move a single whisker to touch? Individuality and stereotypy in behavior

A key function of the brain is to move the body through a rich, complex environment. When rodents engage with their environment, they move their whiskers as they extract tactile information. Even though the study of whisking has a long history, the details of individual whisker movements bilaterally, of nose movement, of stereotypy and variability in an active whisking to touch task are unknown. Here we trained head fixed mice in a simple go-cue task to move a whisker on one side of the face to touch a sensor and tracked facial movements. Our analysis shows that mice specifically control movement of the whisker they use to touch and that as they move their whiskers, they move their nose and apply forces on the head-post in a manner that reflects the behavioral epoch, i.e. whether go cue triggered movement had begun, or a whisker was touching the sensor. Importantly, mice control the setpoint, amplitude and frequency of movement of whiskers bilaterally and individually. Additionally, even though mice achieved the goal of the task -- to touch the sensor within 2 seconds -- how they coordinated movement of the nose and forces on head post with movement of individual whiskers was stereotyped and related to the distance they needed to move a whisker to touch the sensor. Our work shows how stereotyped mouse behavior can be, and it emphasizes both the level of fine motor control mice can exert over individual whiskers and the extent of facial movements in a goal-directed whisking-to-touch task. SignificanceRecent work shows that facial movements are reflected in the activity of a surprisingly large number of brain areas. But what aspects of the face do mice move when they move a whisker to actively touch an object? Our work shows that while mice control the movement of a whisker they use to touch, they also move their nose, apply forces on the head-post and move adjacent whiskers and whiskers on the other side of the face. Additionally, our analysis shows that from day-to-day, this behavior can be surprisingly stereotyped, and that small changes in how far mice move a whisker during tactile behavior fundamentally changes the relationship between the movement of a single whisker and other facial movements.

neuroscience↗

bioRxiv2021

Predicting behavior from eye movement and whisking asymmetry

Navigation through complex environments requires motor planning, motor preparation and the coordination between multiple sensory motor modalities. For example, the stepping motion when we walk is coordinated with motion of the torso, arms, head and eyes. In rodents, movement of the animal through the environment is often coordinated with whisking. Here we trained head fixed mice, navigating a floating Airtrack plus maze, to overcome their directional preference and use cues indicating the direction of movement expected in each trial. Once cued, mice had to move backward out of a lane, then turn in the correct direction, and enter a new lane. In this simple paradigm, as mice begin to move backward, they position their whiskers asymmetrically: whiskers on one side of the face protract, and on the other side they retract. This asymmetry reflected the turn direction. Additionally, on each trial, mice move their eyes conjugately in the direction of the upcoming turn. Not only do they move their eyes, but saccadic eye movement is coordinated with the asymmetric positioning of the whiskers. Our analysis shows that the asymmetric positioning of the whiskers predicts the direction of turn that mice will make at an earlier stage than eye movement does. We conclude that, when mice move or plan to move in complex real-world environments, their motor plan and behavioral state can be read out in the movement of both their whiskers and eyes.

neuroscience↗