Connectivity of pacemaker neurons in the neonatal rat superficial dorsal horn

Abstract

Pacemaker neurons with an intrinsic ability to generate rhythmic burst-firing have been characterized in lamina I of the neonatal spinal cord, where they are innervated by high-threshold sensory afferents. However, little is known about the output of these pacemakers, as the neuronal populations which are targeted by pacemaker axons have yet to be identified. The present study combines patch clamp recordings in the intact neonatal rat spinal cord with tract-tracing to demonstrate that lamina I pacemaker neurons contact multiple spinal motor pathways during early life. Retrograde labeling of premotor interneurons with the trans-synaptic virus PRV-152 revealed the presence of burst-firing in PRV-infected lamina I neurons, thereby confirming that pacemakers are synaptically coupled to motor networks in the spinal ventral horn. Notably, two classes of pacemakers could be distinguished in lamina I based on cell size and the pattern of their axonal projections. While small pacemaker neurons possessed ramified axons which contacted ipsilateral motor circuits, large pacemaker neurons had unbranched axons which crossed the midline and ascended rostrally in the contralateral white matter. Recordings from identified spino-parabrachial and spino-PAG neurons indicated the presence of pacemaker activity within neonatal lamina I projection neurons. Overall, these results show that lamina I pacemakers are positioned to regulate both the level of activity in developing motor circuits as well as the ascending flow of nociceptive information to the brain, thus highlighting a potential role for pacemaker activity in the maturation of pain and sensorimotor networks in the CNS.

Presynaptic Inhibition of Primary Nociceptive Signals to Dorsal Horn Lamina I Neurons by Dopamine

“…Horizontal spinal cord slices, in contrast to coronal or parasagittal slices, offer the unique advantage that afferent fibers, dorsal horn neurons, and dorsal spinal circuits are preserved virtually intact. In horizontal slices, lamina I neurons were visualized through the white matter using infrared light-emitting diode (IR-LED) illumination (Safronov et al, 2007;Szucs et al, 2009;Li et al, 2015b), a CCD video camera (Oly 150; Olympus), and a 40ϫ water-immersion objective mounted on an upright microscope (BX51WI; Olympus). At P18 -P27, the postnatal Figure 1.…”

Inward-rectifying K+ (Kir2) leak conductance dampens the excitability of lamina I projection neurons in the neonatal rat

“…Tissue preparation was performed as previously described (Li et al, 2015). Briefly, DiI injected Sprague-Dawley rats, on P3–P5, were put under a deep plane of anesthesia with sodium pentobarbital (30 mg/kg; Fatal-Plus, Vortec Pharmaceuticals, Dearborn, MI).…”

Stochastic slowly adapting ionic currents may provide a decorrelation mechanism for neural oscillators by causing wander in the intrinsic period

“…Oscillatory neurons are ubiquitous in the basal ganglia, and include dopaminergic neurons in the mesencephalon, tonically active cholinergic neurons in the striatum, as well as the principal neurons in the output nuclei, including the globus pallidus and the substantia nigra par reticulata (Surmeier et al 2005). Pacemakers have also been identified in the inferior olive (Lang 2001), the pons (Williams and Marshall 1987), and the neonatal spinal cord (Li et al 2015). It has been suggested that hippocampal pyramidal neurons may act as autonomous pacemakers under certain conditions in vivo (Yamada-Hanff and Bean 2013).…”