A Functional Topographic Map for Spinal Sensorimotor Reflexes

Computational Modeling of Spinal Locomotor Circuitry in the Age of Molecular Genetics

“…Using neuromechanical models with network models at the level of genetically defined neuronal populations [164] will enable us to directly simulate molecular genetic manipulations and observe behavioral changes (e.g., gaits, kinematics, muscle activities). The need for such detailed neuromechanical models is further amplified by the development of experimental methods to manipulate sensory components of the locomotor system [157,[165][166][167][168][169][170][171]. This includes methods to access muscle spindles [169,172]-even spindles of individual muscles [170]-, proprioceptive feedback [169,173], and interneurons mediating presynaptic inhibition [171] or other sensory processing [166,167].…”

“…The need for such detailed neuromechanical models is further amplified by the development of experimental methods to manipulate sensory components of the locomotor system [157,[165][166][167][168][169][170][171]. This includes methods to access muscle spindles [169,172]-even spindles of individual muscles [170]-, proprioceptive feedback [169,173], and interneurons mediating presynaptic inhibition [171] or other sensory processing [166,167]. The use of these types of integrated neuromechanical models will not just allow simulation of perturbations to any part of the system, but also enable the prediction of resulting temporal dynamics of neuronal activity, muscle activations, and limb kinematics (Figures 1c and 2).…”

Rabies anterograde monosynaptic tracing reveals organization of spinal sensory circuits

“…Second, post-sensory neurons receiving thermal and proprioceptive information are mostly segregated along the dorso-ventral axis highlighting the functional separation of the dorsal and ventral spinal cord for sensory processing and motor control, respectively. Third, at a finer level of resolution, the anatomical organization of post-sensory circuits in the dorsal horn reflects the recently described functional specialization of superficial spinal interneurons in laminae I-IIo for encoding reflexes mediated by inflammatory and noxious stimuli, and of deeper interneurons in laminae IIi-IV for sensory-motor behaviours driven by mechanical inputs (Gatto et al, 2021; Peirs et al, 2021). Interneurons labeled in TRPV1 HTB experiments, that include afferents detecting noxious thermal stimuli are present at higher density in lamina I and IIo, neatly segregated from the ones traced in PV HTB experiments, representing inputs relaying proprioceptive and cutaneous mechanoreceptive information, that are found in deeper layers starting from lamina IIi.…”

“…Recent studies demonstrated the importance of topographic organization of dorsal spinal interneurons for encoding reflexes mediated by inflammatory and noxious stimuli (Gatto et al, 2021; Peirs et al, 2021). Thus, we asked whether the distribution of neurons labelled in PV HTB , TRPV1 HTB , and TRPM8 HTB may reveal the anatomical basis for the functional specificity of spinal somatosensory circuits.…”

Intraspinal injection of adeno-associated viruses into the adult mouse spinal cord

“…A critical factor for successful delivery and expression of fluorescent proteins is the serotype of virus. In spinal cord research, anterogradely transporting AAVs containing the genome of serotype 2 packaged in capsids from serotypes 1, 2, 5, 8, or 9 (AAV2/1, AAV2/2, AAV2/5, AAV2/8, AAV2/9) have been routinely used for the manipulation of spinal neurons or ascending pathways ( Dougherty et al., 2013 ; Fink et al., 2014 ; Bourane et al., 2015 ; Foster et al., 2015 ; Ruder, Takeoka and Arber, 2016 ; Choi et al., 2020 ; Sheahan et al., 2020 ; Barik et al., 2021 ; Gatto et al., 2021 ) ( Figures 1 A and 1B), while AAV retro ( Tervo et al., 2016 ), which is a capsid variant of AAV2, is used for targeting descending neurons ( Esposito et al., 2014 ; Basaldella et al., 2015 ; Murray et al., 2018 ; Sathyamurthy et al., 2020 ; Usseglio et al., 2020 ) ( Figure 1 C). For more information on AAVs, please refer to the following reviews ( Li et al., 2020 ; Naso et al., 2017 ; Samulski and Muzyczka, 2014 ; Wang et al., 2019 ).…”