Properties of synaptic transmission at synapses that formed between dorsal root ganglion (DRG) and dorsal horn (DH) neurons of rats in co-culture were studied. The first 24 sensory synapses are an important site of transmission, integration, and modulation of different types of somatic signaling. Experiments were performed on co-culture of dissociated DRG and DH neurons of newborn rats (14 to 20 days of culturing). Using whole-cell patch-clamp paired recording from DRG and DH neurons, we analyzed monosynaptic EPSCs and IPSCs initiated in DH neurons by action potentials (APs) generated by DRG neurons. Presynaptic DRG neurons were 10-25 мm in diameter and had electrical properties corresponding to nociceptive primary afferent units. Monosynaptic eEPSCs were mediated by activation of AMPA receptors and demonstrated no sensitivity to blockers of NMDA and kainate receptors (20 мM DL-AP5 and 10 мM SIM 2081, respectively), but were entirely blocked upon applications of 10 мM DNQX. Monosynaptic glycinergic eIPSCs found in some of DH neurons were blocked by 1 мM strychnine, and rare found GABAergic eIPSCs were abolished by 10 мM bicuculline. Inhibitory transmission between DRG and DH neurons remained unchanged after blocking of glutamatergic neurotransmission in co-culture. The release of glutamate and glycine at DRG synapses demonstrated a quantal nature. The release properties of these neurotransmitters can be adequately described by simple binomial statistics. The phenomenon of LTD induction of glutamatergic transmission through synapses of primary afferents on DH cells was observed in co-culture. Induction of LTD was provided by low-frequency (5 sec–1) stimulation of single DRG neurons that induced the respective low-frequency AP firing (LFF) in these neurons. LTD induction does not depend on the absence of glycine- and GABAergic transmission at co-cultured neuronal networks and was caused by changes in the properties of DRG synapses. The LTD magnitude and LTD expression mechanisms depended on the LFF duration of a DRG neuron. LFF during 60 sec did not alter the eEPSC amplitudes but significantly increased the coefficient of variation (CV, 56.8±11.5%, n=5;P<0.002) and paired-pulse ratio (PPR, 37.8±11.4%, n=5; P< 0.05), and also decreased the release probability (p, 21.9±5.6%, n=5; P< 0.05) calculated using binomial analysis. This data suggest a presynaptic nature of the changes. LFF for 120 sec led to a decrease of eEPSCs to 14±3.3%, (n=13;P<0.005), but no changes in CV, PPR, and p were found. This is indicative of a postsynaptic nature of LTD expression. LFF for 160, 200, 240, and 360 sec induced robust LTD: eEPSCs decreased to 37.3±4.3% (n=9); 48.1±3.5% (n=7); 58.3±2.5% (n=8), and 57.3±2.8% (n=8), respectively (P<0.001). LTD induced by such LFF durations was not accompanied by significant changes in the PPR and p but showed an increase in the CV (24.4±8.6%, n=6; 35.1±11.2%, n=6; 37.7±12.8%, n=7, and 38.1±9.3, n=8, respectively). The LTD magnitude correlated with the enhancement of CV at different LFF durations (r=0.96). Miniature EPSCs did not change in their amplitude and variability during LTD induced by 5 sec–1 LFF with different durations. These modifications probably resulted from a silencing of functional synapses and/or decrease in the number of release sites at primary afferent synapses. Keywords: synaptic transmission, primary afferents, DRG neurons, dorsal horn neurons, glutamate, glycine, GABA, quantal analysis, synaptic plasticity
