Network-based activity induced by 4-aminopyridine in rat dorsal horn in vitro is mediated by both chemical and electrical synapses

Abstract

This study investigated the role of electrical and chemical synapses in sustaining 4-aminopyridine (4-AP)-evoked network activity recorded extracellularly from substantia gelatinosa (SG) of young rat spinal cord in vitro. Superfusion of 4-AP (50 μM) induced two types of activity, the first was observed as large amplitude field population spiking activity and the second manifested within the inter-spike interval as low amplitude rhythmic oscillations in the 4-12 Hz frequency range (mean peak of 8.0 ± 0.1 Hz). The AMPA/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 μM) abolished field population spiking and disrupted 4-12 Hz rhythmic oscillatory activity whereas the NMDA receptor antagonist d-AP5 (50 μM) had no significant effect on either activity component. The glycine receptor antagonist strychnine (4 μM) and the GABA A receptor antagonist bicuculline (10 μM) diminished and abolished, respectively, field population spiking and both antagonists reduced the power of 4-12 Hz oscillations. The non-specific gap junction blockers carbenoxolone (100 μM) and octanol (1 mM) attenuated both types of 4-AP-induced activity. By comparison, the neuronal-specific gap junction uncouplers quinine (250 μM) and mefloquine (500 nM) both disrupted 4-12 Hz oscillations but only quinine reduced the frequency of field population spiking. These data demonstrate the existence of 4-AP-sensitive neuronal networks within SG that can generate rhythmic activity, are differentially modulated by excitatory and inhibitory ionotropic neurotransmission and are at least partly reliant on neuronal and/or glial-mediated electrical connectivity. The physiological significance of these putative intrinsic SG networks and the implications in the context of processing of nociceptive inputs are discussed. © 2009 The Authors. Journal compilation © 2009 The Physiological Society.