Abstract
Primitive reflexes are evident shortly after birth. Many of these reflexes disappear during postnatal development as part of the maturation of motor control. This study investigates the changes of connectivity related to sensory integration by spinal dI3 interneurons during the time in which the palmar grasp reflex gradually disappears in postnatal mice pups. Our results reveal an increase in GAD65/67-labeled terminals to perisomatic Vglut1-labeled sensory inputs contacting cervical and lumbar dI3 interneurons between postnatal day 3 and day 25. In contrast, there were no changes in the number of perisomatic Vglut1-labeled sensory inputs to lumbar and cervical dI3 interneurons other than a decrease between postnatal day 15 and day 25. Changes in postsynaptic GAD65/67-labeled inputs to dI3 interneurons were inconsistent with a role in the sustained loss of the grasp reflex. These results suggest a possible link between the maturation of hand grasp during postnatal development and increased presynaptic inhibition of sensory inputs to dI3 interneurons.
Highlights
Spinal circuits for movements are established early in development, as evidenced by movements in utero
We show that sensory afferentation onto dI3 interneurons (dI3 INs) is constant throughout early postnatal development but that presynaptic inhibition of primary afferents increases during development
To circumvent any possible developmental adaptations due to this approach, we expressed hM4Di, a Designer Receptor Exclusively Activated by Designer Drugs (DREADD), in Isl1+/Vglut2+ neurons (Figure 1B). dI3 INs could be silenced by JHU37160, a DREADD agonist (Bonaventura et al, 2019)
Summary
Spinal circuits for movements are established early in development, as evidenced by movements in utero. The gating of sensory feedback to spinal circuits is an important spinal mechanism for controlling smooth and coordinated movement (Fink et al, 2014; Koch et al, 2017) One of these gating mechanisms is presynaptic inhibition through axoaxonic GABAergic innervation of the central terminals of sensory afferents (Eccles et al, 1962; Rudomin, 2009; Lalonde and Bui, 2021). Presynaptic inhibition of primary afferents contacting MNs is evident only after the 1st week of postnatal development (Betley et al, 2009; Sonner and Ladle, 2013) This timing roughly coincides with the arrival and establishment of inputs from sensorimotor cortices to the spinal cord (Curfs et al, 1994; Bareyre et al, 2005; Hsu et al, 2006)
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