Biology subjects

Zampieri, N.

Publications and source records attributed to Zampieri, N..

9 recordsLinked to original sources

bioRxiv2026

Walking on the Moon: Hypogravity drives the emergence of a proprioception-dependent locomotor state

Animals must adapt locomotion to changing environmental conditions, but how the nervous system flexibly controls movement remains unclear. Gravity provides a powerful perturbation because it alters body loading, limb dynamics, and proprioceptive feedback. Apollo astronauts often skipped on the Moon, adopting an asymmetric gait rarely used on Earth, yet the sensorimotor basis of this behaviour is unknown. Here, by studying hypogravity locomotion in humans and mice, we show that reduced gravity reveals a conserved proprioception-dependent mechanism for locomotor state expression. In humans, skipping in simulated lunar gravity is generated through flexible temporal reconfiguration of existing motor modules rather than construction of a new motor architecture. In mice, simulated lunar gravity elicited a skipping-like locomotor state, and genetic elimination of muscle proprioceptors abolished this response. Thus, hypogravity reveals how proprioceptive feedback enables flexible expression of locomotor states.

neuroscience↗

bioRxiv2025

Identification of V0g propriospinal neurons and their role in locomotor control

Propriospinal neurons relay sensory and motor information across the spinal cord and are critical components of the circuits coordinating body movements. Their diversity and roles in motor control are not clearly defined yet. In this study, by combining anatomical, molecular, and functional analyses in mice, we identified and characterized an ascending subtype of propriospinal neurons belonging to the Pitx2+ V0 family of spinal neurons. We found that Pitx2+ ascending neurons are integrated in spinal sensorimotor circuits and their function is important for the execution of precise limb movements required for effectively moving in challenging environments, like walking on a horizontal ladder or a balance beam. This work advances our understanding of the functional organization of propriospinal and V0 neurons, highlighting a previously unappreciated role in adjusting body movements to the more demanding needs of skilled locomotor tasks.

neuroscience↗

bioRxiv2023

Catenin signaling controls phrenic motor neuron development and function during a narrow temporal window

Phrenic Motor Column (PMC) neurons are a specialized subset of motor neurons (MNs) that provide the only motor innervation to the diaphragm muscle and are therefore essential for survival. Despite their critical role, the mechanisms that control phrenic MN development and function are not well understood. Here, we show that catenin-mediated cadherin adhesive function is required for multiple aspects of phrenic MN development. Deletion of {beta}- and{gamma} -catenin from MN progenitors results in perinatal lethality and a severe reduction in phrenic MN bursting activity. In the absence of catenin signaling, phrenic MN topography is eroded, MN clustering is lost and phrenic axons and dendrites fail to grow appropriately. Despite the essential requirement for catenins in early phrenic MN development, they appear to be dispensable for phrenic MN maintenance, as catenin deletion from postmitotic MNs does not impact phrenic MN topography or function. Our data reveal a fundamental role for catenins in PMC development and suggest that distinct mechanisms are likely to control PMC maintenance.

neuroscience↗

bioRxiv2022

Coordinated cadherin functions sculpt respiratory motor circuit connectivity

Breathing, and the motor circuits that control it, are essential for life. At the core of respiratory circuits are Dbx1-derived interneurons, which generate the rhythm and pattern of breathing, and phrenic motor neurons (MNs), which provide the final motor output that drives diaphragm muscle contractions during inspiration. Despite their critical function, the principles that dictate how respiratory circuits assemble are unknown. Here we show that coordinated activity of a type I cadherin (N-cadherin) and type II cadherins (Cadherin-6, -9, and -10) is required in both MNs and Dbx1-derived neurons to generate robust respiratory motor output. Both MN- and Dbx1-specific cadherin inactivation during a critical developmental window results in perinatal lethality due to respiratory failure and a striking reduction in phrenic MN bursting activity. This combinatorial cadherin code is required to establish phrenic MN cell body and dendritic topography; surprisingly, however, cell body position appears to be dispensable for the targeting of phrenic MNs by descending respiratory inputs. Our findings demonstrate that type I and type II cadherins function cooperatively throughout the respiratory circuit to generate a robust breathing output and reveal novel strategies that drive the assembly of motor circuits.

neuroscience↗

bioRxiv2022

The molecular foundation of proprioceptor muscle-type identity

The precise execution of coordinated movements depends on proprioception, the sense of body position in space. However, the molecular underpinnings of proprioceptive neuron subtype identities are not clear yet. In this study, we searched for molecular correlates of proprioceptor subtypes defined according to the identity of the muscle they innervate. We identified and validated signatures for subtypes monitoring the activity of back, abdominal, and hindlimb muscles. We found that proprioceptor muscle identity is acquired early in development and comprise programs controlling wiring specificity. Altogether this work paves the way for defining the mechanisms underlying the development of proprioceptor subtypes to the single muscle level and dissect their contributions to motor control.

neuroscience↗

bioRxiv2022

Prox2+ and Runx3+ neurons regulate esophageal motility

Sensory neurons of the vagus nerve monitor distention and stretch in the gastrointestinal tract. Major efforts are underway to assign physiological functions to the many distinct subtypes of vagal sensory neurons. Here, we used genetically guided anatomical tracing, optogenetics and electrophysiology to identify and characterize three vagal sensory neuronal subtypes expressing Prox2 and Runx3. We show that these neuronal subtypes innervate the esophagus and stomach where they display regionalized innervation patterns. Their electrophysiological analysis showed that they are all low threshold mechanoreceptors, but possess different adaptation properties. Lastly, genetic ablation of Prox2+ and Runx3+ neurons demonstrated their essential roles for esophageal peristalsis and swallowing in freely behaving animals. Our work reveals the identity and function of the vagal neurons that provide mechanosensory feedback from the esophagus to the brain, and could lead to better understanding and treatment of esophageal motility disorders.

neuroscience↗

bioRxiv2021

The role of intraspinal sensory neurons in the control of quadrupedal locomotion

From swimming to walking and flying, animals have evolved specific locomotor strategies to thrive in different habitats. All types of locomotion depend on integration of motor commands and sensory information to generate precise movements. Cerebrospinal fluid-contacting neurons (CSF-cN) constitute a vertebrate sensory system that monitors CSF composition and flow. In fish, CSF-cN modulate swimming activity in response to changes in pH and bending of the spinal cord, yet their role in higher vertebrates remains unknown. We used mouse genetics to study their function in quadrupedal locomotion and found that CSF-cN are directly integrated into spinal motor circuits by forming connections with motor neurons and premotor interneurons. Elimination of CSF-cN selectively perturbs the accuracy of foot placement required for skilled movements at the balance beam and horizontal ladder. These results identify an important role for mouse CSF-cN in adaptive motor control and indicate that this sensory system evolved a novel function from lower vertebrates to accommodate the biomechanical requirements of terrestrial locomotion.

neuroscience↗

bioRxiv2021

On the distribution of spinal premotor interneurons

Elaborate behaviours are produced by tightly controlled flexor-extensor motor neuron activation patterns. Motor neurons are regulated by a network of interneurons within the spinal cord, but the computational processes involved in motor control are not fully understood. The neuroanatomical arrangement of motor and premotor neurons into topographic patterns related to their controlled muscles is thought to facilitate how information is processed by spinal circuits. Rabies retrograde monosynaptic tracing has been used to label premotor interneurons innervating specific motor neuron pools, with previous studies reporting topographic mediolateral positional biases in flexor and extensor premotor interneurons. To more precisely define how premotor interneurons contacting specific motor pools are organized we used multiple complementary viral-tracing approaches to minimize systematic biases associated with each method. Contrary to expectations, we found that premotor interneurons contacting motor pools controlling flexion and extension of the ankle are highly intermingled rather than segregated into specific domains like motor neurons. Thus, premotor spinal neurons controlling different muscles process motor instructions in the absence of clear spatial patterns among the flexor-extensor circuit components. The paper can be downloaded in executable format as a MATLAB live script from https://github.com/marcobeato/Spinal_premotor_interneurons_controlling_antagonistic_muscles_are_spatially_intermingled, where all the data are available An R version of the executable paper is available at https://mybinder.org/v2/gh/rronzano/Spinal_premotor_interneurons_controlling_antagonistic_muscles_are_spatially_intermingled.git/HEAD?urlpath=rstudio

neuroscience↗

bioRxiv2021

Rabies anterograde monosynaptic tracing reveals organization of spinal sensory circuits

Somatosensory neurons detect vital information about the environment and internal status of the body, such as temperature, touch, itch and proprioception. The circuit mechanisms controlling the coding of somatosensory information and the generation of appropriate behavioral responses are not clear yet. In order to address this issue, it is important to define the precise connectivity patterns between primary sensory afferents dedicated to the detection of different stimuli and recipient neurons in the central nervous system. In this study we used a rabies tracing approach for mapping spinal circuits receiving sensory input from distinct, genetically defined, modalities. We analyzed the anatomical organization of spinal circuits involved in coding of thermal and mechanical stimuli and showed that somatosensory information from distinct modalities is relayed to partially overlapping ensembles of interneurons displaying stereotyped laminar organization, thus highlighting the importance of positional features and population coding for the processing and integration of somatosensory information.

neuroscience↗