More Like this

1. An information theoretic method to resolve millisecond-scale spike timing precision in a comprehensive motor program

   https://doi.org/10.1371/journal.pcbi.1011170  

   Putney, Joy; Niebur, Tobias; Wood, Leo; Conn, Rachel; Sponberg, Simon (June 2023, PLOS Computational Biology)

   Latham, Peter E. (Ed.)

   Sensory inputs in nervous systems are often encoded at the millisecond scale in a precise spike timing code. There is now growing evidence in behaviors ranging from slow breathing to rapid flight for the prevalence of precise timing encoding in motor systems. Despite this, we largely do not know at what scale timing matters in these circuits due to the difficulty of recording a complete set of spike-resolved motor signals and assessing spike timing precision for encoding continuous motor signals. We also do not know if the precision scale varies depending on the functional role of different motor units. We introduce a method to estimate spike timing precision in motor circuits using continuous MI estimation at increasing levels of added uniform noise. This method can assess spike timing precision at fine scales for encoding rich motor output variation. We demonstrate the advantages of this approach compared to a previously established discrete information theoretic method of assessing spike timing precision. We use this method to analyze the precision in a nearly complete, spike resolved recording of the 10 primary wing muscles control flight in an agile hawk moth, Manduca sexta . Tethered moths visually tracked a robotic flower producing a range of turning (yaw) torques. We know that all 10 muscles in this motor program encode the majority of information about yaw torque in spike timings, but we do not know whether individual muscles encode motor information at different levels of precision. We demonstrate that the scale of temporal precision in all motor units in this insect flight circuit is at the sub-millisecond or millisecond-scale, with variation in precision scale present between muscle types. This method can be applied broadly to estimate spike timing precision in sensory and motor circuits in both invertebrates and vertebrates. 

   more » « less
2. Excitatory and Inhibitory Descending Commissural Interneurons Differentially Integrate Supraspinal and Segmental Sensory Signals

   https://doi.org/10.1523/JNEUROSCI.2015-22.2023  

   Giorgi, Andrea; Cer, Abishag Tluang; Mohan, Shruthi; Perreault, Marie-Claude (June 2023, The Journal of Neuroscience)

   The limited information about how descending inputs from the brain and sensory inputs from the periphery use spinal cord interneurons (INs) is a major barrier to understanding how these inputs may contribute to motor functions under normal and pathologic conditions. Commissural interneurons (CINs) are a heterogeneous population of spinal INs that has been implicated in crossed motor responses and bilateral motor coordination (ability to use the right and left side of the body in a coordinated manner) and, therefore, are likely involved in many types of movement (e.g., dynamic posture stabilization, jumping, kicking, walking). In this study, we incorporate mouse genetics, anatomy, electrophysiology, and single-cell calcium imaging to investigate how a subset of CINs, those with descending axons called dCINs, are recruited by descending reticulospinal and segmental sensory signals independently and in combination. We focus on two groups of dCINs set apart by their principal neurotransmitter (glutamate and GABA) and identified as VGluT2+ dCINs and GAD2+ dCINs. We show that VGluT2+ and GAD2+ dCINs are both extensively recruited by reticulospinal and sensory input alone but that VGluT2+ and GAD2+ dCINs integrate these inputs differently. Critically, we find that when recruitment depends on the combined action of reticulospinal and sensory inputs (subthreshold inputs), VGluT2+ dCINs, but not GAD2+ dCINs, are recruited. This difference in the integrative capacity of VGluT2+ and GAD2+ dCINs represents a circuit mechanism that the reticulospinal and segmental sensory systems may avail themselves of to regulate motor behaviors both normally and after injury. SIGNIFICANCE STATEMENTThe way supraspinal and peripheral sensory inputs use spinal cord interneurons is fundamental to defining how motor functions are supported both in health and disease. This study, which focuses on dCINs, a heterogeneous population of spinal interneurons critical for crossed motor responses and bilateral motor coordination, shows that both glutamatergic (excitatory) and GABAergic (inhibitory) dCINs can be recruited by supraspinal (reticulospinal) or peripheral sensory inputs. Additionally, the study demonstrates that in conditions where the recruitment of dCINs depends on the combined action of reticulospinal and sensory inputs, only excitatory dCINs are recruited. The study uncovers a circuit mechanism that the reticulospinal and segmental sensory systems may avail themselves of to regulate motor behaviors both normally and after injury. 

   more » « less
3. The processing of proprioceptive signals in distributed networks: insights from insect motor control

   https://doi.org/10.1242/jeb.246182  

   Gebehart, Corinna; Büschges, Ansgar (January 2024, Journal of Experimental Biology)

   ABSTRACT The integration of sensory information is required to maintain body posture and to generate robust yet flexible locomotion through unpredictable environments. To anticipate required adaptations in limb posture and enable compensation of sudden perturbations, an animal's nervous system assembles external (exteroception) and internal (proprioception) cues. Coherent neuronal representations of the proprioceptive context of the body and the appendages arise from the concerted action of multiple sense organs monitoring body kinetics and kinematics. This multimodal proprioceptive information, together with exteroceptive signals and brain-derived descending motor commands, converges onto premotor networks – i.e. the local neuronal circuitry controlling motor output and movements – within the ventral nerve cord (VNC), the insect equivalent of the vertebrate spinal cord. This Review summarizes existing knowledge and recent advances in understanding how local premotor networks in the VNC use convergent information to generate contextually appropriate activity, focusing on the example of posture control. We compare the role and advantages of distributed sensory processing over dedicated neuronal pathways, and the challenges of multimodal integration in distributed networks. We discuss how the gain of distributed networks may be tuned to enable the behavioral repertoire of these systems, and argue that insect premotor networks might compensate for their limited neuronal population size by, in comparison to vertebrate networks, relying more heavily on the specificity of their connections. At a time in which connectomics and physiological recording techniques enable anatomical and functional circuit dissection at an unprecedented resolution, insect motor systems offer unique opportunities to identify the mechanisms underlying multimodal integration for flexible motor control. 

   more » « less
4. Neural circuit regulation by identified modulatory projection neurons

   https://doi.org/10.3389/fnins.2023.1154769  

   Blitz, Dawn M. (March 2023, Frontiers in Neuroscience)

   Rhythmic behaviors (e.g., walking, breathing, and chewing) are produced by central pattern generator (CPG) circuits. These circuits are highly dynamic due to a multitude of input they receive from hormones, sensory neurons, and modulatory projection neurons. Such inputs not only turn CPG circuits on and off, but they adjust their synaptic and cellular properties to select behaviorally relevant outputs that last from seconds to hours. Similar to the contributions of fully identified connectomes to establishing general principles of circuit function and flexibility, identified modulatory neurons have enabled key insights into neural circuit modulation. For instance, while bath-applying neuromodulators continues to be an important approach to studying neural circuit modulation, this approach does not always mimic the neural circuit response to neuronal release of the same modulator. There is additional complexity in the actions of neuronally-released modulators due to: (1) the prevalence of co-transmitters, (2) local- and long-distance feedback regulating the timing of (co-)release, and (3) differential regulation of co-transmitter release. Identifying the physiological stimuli (e.g., identified sensory neurons) that activate modulatory projection neurons has demonstrated multiple “modulatory codes” for selecting particular circuit outputs. In some cases, population coding occurs, and in others circuit output is determined by the firing pattern and rate of the modulatory projection neurons. The ability to perform electrophysiological recordings and manipulations of small populations of identified neurons at multiple levels of rhythmic motor systems remains an important approach for determining the cellular and synaptic mechanisms underlying the rapid adaptability of rhythmic neural circuits. 

   more » « less
5. Organization of an ascending circuit that conveys flight motor state in Drosophila

   https://doi.org/10.1016/j.cub.2024.01.071  

   Cheong, Han S.J.; Boone, Kaitlyn N.; Bennett, Marryn M.; Salman, Farzaan; Ralston, Jacob D.; Hatch, Kaleb; Allen, Raven F.; Phelps, Alec M.; Cook, Andrew P.; Phelps, Jasper S.; et al (March 2024, Current Biology)

   Natural behaviors are a coordinated symphony of motor acts that drive reafferent (self-induced) sensory activation. Individual sensors cannot disambiguate exafferent (externally induced) from reafferent sources. Nevertheless, animals readily differentiate between these sources of sensory signals to carry out adaptive behaviors through corollary discharge circuits (CDCs), which provide predictive motor signals from motor pathways to sensory processing and other motor pathways. Yet, how CDCs comprehensively integrate into the nervous system remains unexplored. Here, we use connectomics, neuroanatomical, physiological, and behavioral approaches to resolve the network architecture of two pairs of ascending histaminergic neurons (AHNs) in Drosophila, which function as a predictive CDC in other insects. Both AHN pairs receive input primarily from a partially overlapping population of descending neurons, especially from DNg02, which controls wing motor output. Using Ca2+ imaging and behavioral recordings, we show that AHN activation is correlated to flight behavior and precedes wing motion. Optogenetic activation of DNg02 is sufficient to activate AHNs, indicating that AHNs are activated by descending commands in advance of behavior and not as a consequence of sensory input. Downstream, each AHN pair targets predominantly non-overlapping networks, including those that process visual, auditory, and mechanosensory information, as well as networks controlling wing, haltere, and leg sensorimotor control. These results support the conclusion that the AHNs provide a predictive motor signal about wing motor state to mostly non-overlapping sensory and motor networks. Future work will determine how AHN signaling is driven by other descending neurons and interpreted by AHN downstream targets to maintain adaptive sensorimotor performance. 

   more » « less