Biology subjects

Akay, T.

Publications and source records attributed to Akay, T..

11 recordsLinked to original sources

bioRxiv2026

Posture and support geometry, rather than body size, dictate lateral dynamic stability in walking mammalian quadrupeds

Body size and limb posture vary widely across mammals and are expected to shape locomotor stability, yet direct comparative evidence remains limited. Here, we tested whether smaller, crouched mammals exhibit greater lateral dynamic stability than larger, more upright species by comparing treadmill walking in mice and cats at dynamically similar speeds. Using kinematic analyses and size normalized measures of stability, we show that mice are substantially more laterally stable than cats. This increased stability is associated with relatively wider step widths and more crouched limb posture, indicating that support geometry and posture play dominant roles in stabilizing locomotion. Despite these differences, both species regulate lateral balance on a step-by-step basis, as revealed by relationships between center of mass motion and subsequent adjustments of the border of support. Our findings demonstrate that locomotor stability does not scale simply with body size but depends critically on posture dependent strategies that differ across species. These results identify lateral stability as a key factor of locomotor adaptation and suggest that crouched postures in small mammals may reduce reliance on active neural control while enhancing robustness in complex environments. SUMMARY STATEMENTLateral dynamic stability during quadrupedal locomotion depends primarily on limb posture and support geometry rather than body size. Smaller mammals achieve greater stability through crouched postures and wider step widths, whereas larger mammals operate closer to stability limits and rely more heavily on active control.

neuroscience↗

bioRxiv2025

Evidence of spinal cord comparator modules for rapid corrections of movements

Successful movement requires continuous adjustments in response to changes in internal and external environments. To do so, neural circuits continuously compare efference copies of motor commands with sensory feedback to respond to sensory prediction errors. Some responses need to be very fast, indicating that they likely occur within spinal cord circuits. Here, we describe spinal cord circuits involving dI3 neurons, showing that they receive multimodal sensory inputs and direct efferent copies from both Renshaw cells and motor neurons. We further show that they form connections to motor pools. Reducing dI3 neuronal activity diminished stumbling responses, as did disrupting Renshaw cell circuits, providing evidence for a comparator role of dI3 neurons for online corrections. Together, our findings reveal a pivotal role for dI3 neurons functioning as comparators of efference copies and external sensory feedback to mediate rapid corrections of ongoing movements.

neuroscience↗

bioRxiv2025

Task-specificity of local load feedback depends on intersegmental information in an insect walking system

Load proprioceptive feedback measured by campaniform sensilla (CS) substantially contributes to the generation of leg stepping during walking. In stick insects, the effect of load feedback on the antagonistic protractor and retractor motor neurons (MNs) reverses depending on the walking direction to support the functional stance MN pool in both stepping directions. However, this was shown in highly reduced preparations in which the stimulated leg did not perform actual stepping movements, but the effect was inferred from MN activity profiles. It is still largely unknown whether the load feedback similarly shows a direction dependent reversal in its effects on protractor and retractor activity during actual stepping of the stimulated leg. Here, we implemented load stimulation in a single-middle leg preparation and recorded protractor and retractor MN activity extracellularly during fictive forward and backward stepping. We show that CS stimulation during the stance phase prolonged stance (retractor) activity for the duration of the stimulation and induced stance (retractor) activity when applied during the swing phase in forward stepping. During backward stepping, when protractor and retractor switch phases, the same stimulation again prolonged stance (protractor) activity for the duration of the stimulation. However, it rarely induced stance (protractor) activity when applied during the swing phase. We provide evidence that this is due to the absence of signals about the stepping direction of the neighboring legs, thus highlighting the importance of intersegmental signals for task-specific processing of load proprioceptive feedback. New and NoteworthyProprioceptive feedback needs to be processed in a task-dependent manner to serve its function, even when the leg kinematics change to generate different behaviors. We show for forward and backward stepping that load signals initiate and maintain the activity of the functional stance phase motor neuron pool and that intersegmental signals about stepping of the neighboring legs are relevant for the task-specific processing of load feedback.

neuroscience↗

bioRxiv2024

Widespread innervation of motoneurons by spinal V3 neurons globally amplifies locomotor output in mice.

While considerable progress has been made in understanding the neuronal circuits that underlie the patterning of locomotor behaviours such as walking, less is known about the circuits that amplify motoneuron output to enable adaptable increases in muscle force across different locomotor intensities. Here, we demonstrate that an excitatory propriospinal neuron population (V3 neurons, Sim1+) forms a large part of the total excitatory interneuron input to motoneurons ([~]20%) across all hindlimb muscles. Additionally, V3 neurons make extensive connections among themselves and with other excitatory premotor neurons (such as V2a neurons). These circuits allow local activation of V3 neurons at just one segment (via optogenetics) to rapidly depolarize and amplify locomotor-related motoneuron output at all lumbar segments in both the in vitro spinal cord and the awake adult mouse. Interestingly, despite similar innervation from V3 neurons to flexor and extensor motoneuron pools, functionally, V3 neurons exhibit a pronounced bias towards activating extensor muscles. Furthermore, the V3 neurons appear essential to extensor activity during locomotion because genetically silencing them leads to slower and weaker mice with a poor ability to increase force with locomotor intensity, without much change in the timing of locomotion. Overall, V3 neurons increase the excitability of motoneurons and premotor neurons, thereby serving as global command neurons that amplify the locomotion intensity.

neuroscience↗

bioRxiv2023

Distinct roles of spinal commissural interneurons in transmission of contralateral sensory information

Crossed reflexes (CR) are mediated by commissural pathways transmitting sensory information to the contralateral side of the body, but the underlying network is not fully understood. Commissural pathways coordinating the activities of spinal locomotor circuits during locomotion have been characterized in mice, but their relationship to CR is unknown. We show the involvement of two genetically distinct groups of commissural interneurons (CINs) described in mice, V0 and V3 CINs, in the CR pathways. Our data suggest that the exclusively excitatory V3 CINs are directly involved in the excitatory CR, and show that they are essential for the inhibitory CR. In contrast, the V0 CINs, a population that includes excitatory and inhibitory CINs, are not directly involved in excitatory or inhibitory CRs but down-regulate the inhibitory CR. Our data provide insights into the spinal circuitry underlying CR in mice, describing the roles of V0 and V3 CINs in CR.

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bioRxiv2022

Inhibitory interneurons within the deep dorsal horn integrate convergent sensory input to regulate motor performance

To achieve smooth motor performance in a changing sensory environment, motor outputs must be constantly updated in response to sensory feedback. Inhibitory interneurons in the spinal cord play an essential role in shaping motor activity by gating the transmission of sensory information and setting the pattern and rhythm of motor neurons. Here, we identify the medial deep dorsal horn of the spinal cord as a "hot zone" of convergent proprioceptive and cutaneous information from the hindlimb, where inhibitory neurons show increased responsiveness to sensory input and are preferentially recruited during locomotion in comparison to excitatory neurons. We identify a novel population of glycinergic inhibitory neurons within the deep dorsal horn that express parvalbumin (dPV) and receive convergent proprioceptive and cutaneous input from the paw. We show that dPVs possess intrinsic properties that support spontaneous discharge, even in the absence of synaptic input. However, a drug cocktail mimicking descending input (5-HT, dopamine, NMDA) amplifies dPV output, while cutaneous and proprioceptive inputs shape the temporal dynamics of dPV activity. These findings suggest dPV-mediated inhibition is modulated by behavioral state and can be fine-tuned by sensory input. Using intersectional genetic strategies, we selectively target spinal cord dPVs and demonstrate their capacity to provide divergent ipsilateral inhibition to both pre-motor and motor networks of the ventral horn, thereby controlling the timing and magnitude of cutaneous-evoked muscle activity. Manipulating the activity of dPVs during treadmill locomotion results in altered limb kinematics at the transition of stance to swing and altered step cycle timing at increased speeds. To investigate the effects of manipulating dPV activity on broader sets of motor behaviors, we used depth vision and machine learning to quantify and scale naturalistic behavior. We find that although sub-movements remain stable, the transitions between sub-movements are reduced, suggesting a role in movement switching. In sum, our study reveals a new model by which sensory convergence and inhibitory divergence produce a surprisingly flexible influence on motor networks to increase the diversity of mechanisms by which sensory input facilitates smooth movement and context-appropriate transitions. HighlightsO_LIInhibitory deep dorsal horn interneurons integrate convergent proprioceptive and cutaneous sensory inputs from the paw and are preferentially recruited during locomotion. C_LIO_LIDeep dorsal horn parvalbumin+ interneurons (dPVs) represent a population of glycinergic interneurons that can provide sustained inhibitory control. C_LIO_LISensory input engages dPVs to facilitate inhibition with high temporal precision and reduced variability. C_LIO_LIdPVs contribute to the ipsilateral inhibitory control of motor and premotor networks of the ventral horn, thereby gating the magnitude and timing of cutaneous-evoked flexor and extensor muscle activity. C_LIO_LIIn vivo, dPVs modulate gait dynamics in a state- and phase-dependent manner, to ensure smooth movement transitions between step-cycle phases and naturalistic sub-movements. C_LI

neuroscience↗

bioRxiv2022

Orphan nuclear receptors Err2 and 3 promote a feature-specific terminal differentiationprogram underlying gamma motor neuron function and proprioceptive movement control

Motor neurons are commonly thought of as mere relays between the central nervous system and the movement apparatus, yet, in mammals about one-third of them function exclusively as regulators of muscle proprioception. How these gamma motor neurons acquire properties to function differently from the muscle force-producing alpha motor neurons remains unclear. Here, we found that upon selective loss of the orphan nuclear receptors Err2 and Err3 (Err2/3) in mice, gamma motor neurons acquire characteristic structural (e.g. synaptic wiring), but not functional (e.g. physiological firing rates) properties necessary for regulating muscle proprioception, thus disrupting gait and precision movements in vivo. Moreover, Err2/3 operate via transcriptional activation of neural activity modulators, one of which (Kcna10) promoted gamma motor neuron functional properties. Our work identifies a long-sought mechanism specifying gamma motor neuron properties necessary for proprioceptive movement control, which implies a feature-specific terminal differentiation program implementing neuron subtype-specific functional but not structural properties. SummaryThe transcription factors Err2 and 3 promote functional properties in a subset of motor neurons necessary for executing precise movements.

neuroscience↗

bioRxiv2021

Differential role of spinal and supraspinal processing of proprioceptive information in mouse locomotion

Robust locomotion relies on information from proprioceptors: sensory organs that communicate the position of body parts to the spinal cord and brain. Proprioceptive circuits in the spinal cord are known to regulate locomotion in challenging environments. Yet, the regulatory importance of the brain remains less clear. Here, through mouse genetic studies and in vivo electrophysiology, we examined the role of the brain in integrating proprioceptive information during locomotion. The systemic removal of proprioceptors left the animals in a constantly perturbed state, similar to that observed during mechanically perturbed locomotion in wild type and characterised by longer and less accurate activation patterns. In contrast, after surgically interrupting the ascending proprioceptive projection to the brain through the dorsal column pathway, wild-type mice showed normal walking behaviour, but lost the ability to respond to external perturbations. Our findings provide direct evidence of a pivotal role for ascending proprioceptive information in achieving safe locomotion.

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bioRxiv2020

Freely behaving mice can brake and turn during optogenetic stimulation of the Mesencephalic Locomotor Region

AO_SCPLOWBSTRACTC_SCPLOWO_ST_ABSBackgroundC_ST_ABSStimulation of the Mesencephalic Locomotor Region (MLR) is increasingly considered as a target to improve locomotor function in Parkinsons disease, spinal cord injury and stroke. A key function of the MLR is to control the speed of forward symmetrical locomotor movements. However, the ability of freely moving mammals to integrate environmental cues to brake and turn during MLR stimulation is poorly documented. Objective/hypothesisWe investigated whether freely behaving mice could brake or turn based on environmental cues during MLR stimulation. MethodsWe stimulated the cuneiform nucleus in mice expressing channelrhodopsin in Vglut2-positive neurons in a Cre-dependent manner (Vglut2-ChR2-EYFP) using optogenetics. We detected locomotor movements using deep learning. We used patch-clamp recordings to validate the functional expression of channelrhodopsin and neuroanatomy to visualize the stimulation sites. ResultsOptogenetic stimulation of the MLR evoked locomotion and increasing laser power increased locomotor speed. Gait diagram and limb kinematics were similar during spontaneous and optogenetic-evoked locomotion. Mice could brake and make sharp turns ([~]90) when approaching a corner during MLR stimulation in an open-field arena. The speed during the turn was scaled with the speed before the turn, and with the turn angle. In a reporter mouse, many Vglut2-ZsGreen neurons were immunopositive for glutamate in the MLR. Patch-clamp recordings in Vglut2-ChR2-EYFP mice show that blue light evoked short latency spiking in MLR neurons. ConclusionMLR glutamatergic neurons are a relevant target to improve locomotor activity without impeding the ability to brake and turn when approaching an obstacle, thus ensuring smooth and adaptable navigation. HO_SCPLOWIGHLIGHTSC_SCPLOW- Mice brake and turn when approaching the arenas corner during MLR-evoked locomotion - Speed decrease is scaled to speed before the turn during MLR-evoked locomotion - Turn angle is scaled to turn speed during MLR-evoked locomotion - Gait and limb kinematics are similar during spontaneous and MLR-evoked locomotion

neuroscience↗

bioRxiv2020

Fractal analysis of muscle activity patterns during locomotion: pitfalls and how to avoid them

Time-dependent physiological data, such as electromyogram (EMG) recordings from multiple muscles, is often difficult to interpret objectively. Here, we used EMG data gathered during mouse locomotion to investigate the effects of calculation parameters and data quality on two metrics for fractal analysis: the Higuchis fractal dimension (HFD) and the Hurst exponent (H). A curve is fractal if it repeats itself at every scale or, in other words, if its shape remains unchanged when zooming in the curve at every zoom level. Many linear and nonlinear analysis methods are available, each of them aiming at the explanation of different data features. In recent years, fractal analysis has become a powerful nonlinear tool to extract information from physiological data not visible to the naked eye. It can present, however, some dangerous pitfalls that can lead to misleading interpretations. To calculate the HFD and the H, we have extracted muscle synergies from normal and mechanically perturbed treadmill locomotion from the hindlimb of adult mice. Then, we used one set per condition (normal and perturbed walking) of the obtained time-dependent coefficients to create surrogate data with different fluctuations over the original mean signal. Our analysis shows that HFD and H are exceptionally sensitive to the presence or absence of perturbations to locomotion. However, both metrics suffer from variations in their value depending on the parameters used for calculations and the presence of quasi-periodic elements in the time series. We discuss those issues giving some simple suggestions to reduce the chance of misinterpreting the outcomes. New & NoteworthyDespite the lack of consensus on how to perform fractal analysis of physiological time series, many studies rely on this technique. Here, we shed light on the potential pitfalls of using the Higuchis fractal dimension and the Hurst exponent. We expose and suggest how to solve the drawbacks of such methods when applied to data from normal and perturbed locomotion by combining in vivo recordings and computational approaches.

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bioRxiv2018

Modular organization of the murine locomotor pattern in presence and absence of sensory feedback from muscle spindles

For exploiting terrestrial and aquatic locomotion, vertebrates must build their locomotor patterns based on an enormous amount of variables. The great number of muscles and joints, together with the constant need for sensory feedback information (e.g. proprioception), make the task of creating and controlling movement a problem with overabundant degrees of freedom. It is widely accepted that the central nervous system might simplify the creation and control of movement. This could happen through the generation of activation patterns, which are common to many different muscles, rather than specific to individual muscles. These activation patterns, called muscle synergies, can be extracted from electromyographic data and describe the modular organization of movement. We extracted muscle synergies from the hindlimb muscle activities of wild type and genetically modified mice, in which sensory feedback from muscle spindles is eliminated. Muscle spindle-deficient mice underwent a modification of the temporal structure (motor primitives) of muscle synergies that resulted in diminished functionality during walking. In addition, both the temporal and spatial components (motor modules) of muscle synergies were severely affected when external perturbations were introduced of when animals were immersed in water. These findings show that group Ia/II sensory feedback from muscle spindles regulates motor function in normal and perturbed walking. Moreover, when group Ib Golgi tendon organ feedback is lacking due to the reduction of gravitational load in conditions of enhanced buoyancy, the modular organization of swimming is almost completely compromised.\n\nSignificance statementLocomotion on land and in water requires the coordination of a great number of muscle activations and joint movements. Moreover, constant feedback about the position of own body parts in relation to the surrounding environment and the body itself (proprioception) is required to maintain stability and avoid failure. The theory of muscle synergies states that the central nervous system might control muscles in orchestrated groups (synergies) rather than individually. We used this concept on genetically modified mice, lacking one of the two classes of proprioceptors. Our results provide evidence that proprioceptive feedback is required by the central nervous system to accurately tune the modular organization of locomotion.

neuroscience↗