Functional GABAA-Receptor–Mediated Inhibition in the Neonatal Dorsal Horn

Abstract

Neonatal nociceptive circuits and dorsal horn cells are characterized by an apparent lack of inhibitory control: receptive fields are large and thresholds low in the first weeks of life. It has been suggested that this may reflect immature GABA_A-receptor (GABA_AR) signaling whereby an early developmental shift in transmembrane anion gradient is followed by a longer period of low Cl⁻ extrusion capacity. To investigate whether functional GABA_AR-mediated inhibition does indeed undergo postnatal regulation at the level of dorsal horn circuits, we applied the selective GABA_AR antagonist gabazine to the spinal cord in anesthetized rat pups [postnatal day (P) 3 or 21] while recording spike activity in single lumbar dorsal horn cells in vivo. At both ages, blockade of GABA_AR activity resulted in enlarged hind paw receptive field areas and increased activity evoked by low- and high-intensity cutaneous stimulation, revealing comparable inhibition of dorsal horn cell firing by spinal GABA_ARs at P3 and P21. This inhibition did not require descending pathways to the spinal cord because perforated patch-clamp recordings of deep dorsal horn neurons in P3 spinal cord slices also showed an increase in evoked spike activity after application of gabazine. We conclude that spinal GABAergic inhibitory transmission onto single dorsal horn cells “in vivo” is functional at P3 and that low Cl⁻ extrusion capacity does not restrict GABAergic function over the normal range of evoked sensory activity. The excitability of neonatal spinal sensory circuits could reflect immaturity in other intrinsic or descending inhibitory networks rather than weak spinal GABAergic inhibition.