Faculty Opinions recommendation of Mechanosensory input during circuit formation shapes Drosophila motor behavior through patterned spontaneous network activity.

Author(s):  
Emmanuel Farge
2021 ◽  
Author(s):  
Arnaldo Carreira-Rosario ◽  
Ryan A York ◽  
Minseung Choi ◽  
Chris Q Doe ◽  
Thomas R Clandinin

Neural activity sculpts circuit wiring in many animals. In vertebrates, patterned spontaneous network activity (PaSNA) generates sensory maps and establishes local circuits. However, it remains unclear how PaSNA might shape neuronal circuits and behavior in invertebrates. Previous work in the developing Drosophila embryo discovered spontaneous muscle activity that did not require synaptic transmission, and hence was myogenic, preceding PaSNA. These studies, however, monitored muscle movement, not neural activity, and were therefore unable to observe how myogenic activity might relate to subsequent neural network engagement. Here we use calcium imaging to directly record neural activity and characterize the emergence of PaSNA. We demonstrate that the spatiotemporal properties of PaSNA are highly stereotyped across embryos, arguing for genetic programming. Consistent with previous observations, we observe neural activity well before it becomes patterned, initially emerging during the myogenic stage. Remarkably, inhibition of mechanosensory input results in excessive PaSNA, demonstrating that muscle movement serves as a brake. Finally, using an optogenetic strategy to selectively disrupt mechanosensory inputs during PaSNA, followed by quantitative modeling of larval behavior, we demonstrate that mechanosensory modulation during development is required for proper larval foraging. This work thus provides a foundation for using the Drosophila embryo to study the role of PaSNA in circuit formation, provides mechanistic insight into how PaSNA is entrained by motor activity, and demonstrates that spontaneous network activity is essential for locomotor behavior. These studies argue that sensory feedback during the earliest stages of circuit formation can sculpt locomotor behaviors through innate motor learning.


2021 ◽  
Author(s):  
Arnaldo Carreira-Rosario ◽  
Ryan A. York ◽  
Minseung Choi ◽  
Chris Q. Doe ◽  
Thomas R. Clandinin

2019 ◽  
Author(s):  
Riazul Islam ◽  
Carlos Cuellar ◽  
Ben Felmlee ◽  
Tori Riccelli ◽  
Jodi Silvernail ◽  
...  

AbstractIntegrating multiple assessment parameters of motor behavior is critical for understanding neural activity dynamics during motor control in both intact and dysfunctional nervous systems. Here, we described a novel approach (termed Multifactorial Behavioral Assessment (MfBA)) to integrate, in real-time, electrophysiological and biomechanical properties of rodent spinal sensorimotor network activity with behavioral aspects of motor task performance. Specifically, the MfBA simultaneously records limb kinematics, multi-directional forces and electrophysiological metrics, such as high-fidelity chronic intramuscular electromyography synchronized in time to spinal stimulation in order to characterize spinal cord functional motor evoked potentials (fMEPs). Additionally, we designed the MfBA to incorporate a body weight support system to allow bipedal and quadrupedal stepping on a treadmill and in an open field environment to assess function in rodent models of neurologic disorders that impact motor activity This novel approach was validated using, a neurologically intact cohort, a cohort with unilateral Parkinsonian motor deficits due to midbrain lesioning, and a cohort with complete hind limb paralysis due to T8 spinal cord transection. In the SCI cohort, lumbosacral epidural electrical stimulation (EES) was applied, with and without administration of the serotonergic agonist Quipazine, to enable hind limb motor functions following paralysis. The results presented herein demonstrate the MfBA is capable of integrating multiple metrics of motor activity in order to characterize relationships between EES inputs that modulate mono- and polysynaptic outputs from spinal circuitry which in turn, can be used to elucidate underlying electrophysiologic mechanisms of motor behavior by synchronizing these datasets to metrics of movement and behavior. These results also demonstrate that proposed MfBA is an effective tool to integrate biomechanical and electrophysiology metrics, synchronized to therapeutic inputs such as EES or pharmacology, during body weight supported treadmill or open field motor activities, to target a high range of variations in motor behavior as a result of neurological deficit at the different levels of CNS.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Riazul Islam ◽  
Carlos A. Cuellar ◽  
Ben Felmlee ◽  
Tori Riccelli ◽  
Jodi Silvernail ◽  
...  

Abstract Integrating multiple assessment parameters of motor behavior is critical for understanding neural activity dynamics during motor control in both intact and dysfunctional nervous systems. Here, we described a novel approach (termed Multifactorial Behavioral Assessment (MfBA)) to integrate, in real-time, electrophysiological and biomechanical properties of rodent spinal sensorimotor network activity with behavioral aspects of motor task performance. Specifically, the MfBA simultaneously records limb kinematics, multi-directional forces and electrophysiological metrics, such as high-fidelity chronic intramuscular electromyography synchronized in time to spinal stimulation in order to characterize spinal cord functional motor evoked potentials (fMEPs). Additionally, we designed the MfBA to incorporate a body weight support system to allow bipedal and quadrupedal stepping on a treadmill and in an open field environment to assess function in rodent models of neurologic disorders that impact motor activity. This novel approach was validated using, a neurologically intact cohort, a cohort with unilateral Parkinsonian motor deficits due to midbrain lesioning, and a cohort with complete hind limb paralysis due to T8 spinal cord transection. In the SCI cohort, lumbosacral epidural electrical stimulation (EES) was applied, with and without administration of the serotonergic agonist Quipazine, to enable hind limb motor functions following paralysis. The results presented herein demonstrate the MfBA is capable of integrating multiple metrics of motor activity in order to characterize relationships between EES inputs that modulate mono- and polysynaptic outputs from spinal circuitry which in turn, can be used to elucidate underlying electrophysiologic mechanisms of motor behavior. These results also demonstrate that proposed MfBA is an effective tool to integrate biomechanical and electrophysiology metrics, synchronized to therapeutic inputs such as EES or pharmacology, during body weight supported treadmill or open field motor activities, to target a high range of variations in motor behavior as a result of neurological deficit at the different levels of CNS.


2021 ◽  
Author(s):  
Arnaldo Carreira-Rosario ◽  
Ryan A. York ◽  
Minseung Choi ◽  
Chris Q. Doe ◽  
Tom Clandinin

1998 ◽  
Vol 79 (5) ◽  
pp. 2804-2808 ◽  
Author(s):  
Jason N. Maclean ◽  
Kristine C. Cowley ◽  
Brian J. Schmidt

MacLean, Jason N., Kristine C. Cowley, and Brian J. Schmidt. NMDA receptor-mediated oscillatory activity in the neonatal rat spinal cord is serotonin dependent. J. Neurophysiol. 79: 2804–2808, 1998. The effect of serotonin (5-HT) receptor blockade on rhythmic network activity and on N-methyl-d-aspartate (NMDA) receptor-induced membrane voltage oscillations was examined using an in vitro neonatal rat spinal cord preparation. Pharmacologically induced rhythmic hindlimb activity, monitored via flexor and extensor electroneurograms or ventral root recordings, was abolished by 5-HT receptor antagonists. Intrinsic motoneuronal voltage oscillations, induced by NMDA in the presence of tetrodotoxin (TTX), either were abolished completely or transformed to long-lasting voltage shifts by 5-HT receptor antagonists. Conversely, 5-HT application facilitated the expression of NMDA-receptor–mediated rhythmic voltage oscillations. The results suggest that an interplay between 5-HT and NMDA receptor actions may be critical for the production of rhythmic motor behavior in the mammalian spinal cord, both at the network and single cell level.


2010 ◽  
Vol 24 (2) ◽  
pp. 76-82 ◽  
Author(s):  
Martin M. Monti ◽  
Adrian M. Owen

Recent evidence has suggested that functional neuroimaging may play a crucial role in assessing residual cognition and awareness in brain injury survivors. In particular, brain insults that compromise the patient’s ability to produce motor output may render standard clinical testing ineffective. Indeed, if patients were aware but unable to signal so via motor behavior, they would be impossible to distinguish, at the bedside, from vegetative patients. Considering the alarming rate with which minimally conscious patients are misdiagnosed as vegetative, and the severe medical, legal, and ethical implications of such decisions, novel tools are urgently required to complement current clinical-assessment protocols. Functional neuroimaging may be particularly suited to this aim by providing a window on brain function without requiring patients to produce any motor output. Specifically, the possibility of detecting signs of willful behavior by directly observing brain activity (i.e., “brain behavior”), rather than motoric output, allows this approach to reach beyond what is observable at the bedside with standard clinical assessments. In addition, several neuroimaging studies have already highlighted neuroimaging protocols that can distinguish automatic brain responses from willful brain activity, making it possible to employ willful brain activations as an index of awareness. Certainly, neuroimaging in patient populations faces some theoretical and experimental difficulties, but willful, task-dependent, brain activation may be the only way to discriminate the conscious, but immobile, patient from the unconscious one.


1981 ◽  
Vol 26 (4) ◽  
pp. 258-259
Author(s):  
Jack A. Adams
Keyword(s):  

1981 ◽  
Vol 26 (11) ◽  
pp. 884-884
Author(s):  
Waneen Wyrick Spirduso
Keyword(s):  

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