In vitro brain slice studies of the rat's dorsal nucleus of the lateral lemniscus. III. synaptic pharmacology.

1. The synaptic pharmacology of the dorsal nucleus of the lateral lemniscus (DNLL) of the rat was investigated in a brain slice preparation of the auditory midbrain. The brain slice was cut in the coronal plane and placed in a small recording chamber where warm, oxygenated saline was continuously perfused over and underneath the tissue. Intracellular recordings were made with glass microelectrodes filled with 4 M potassium acetate. Synaptic potentials were elicited by electrical stimulation of the lateral lemniscus or commissure of Probst and pharmacological effects were tested by bath application of amino acid agonists and antagonists. 2. The cells in DNLL were challenged with the excitatory amino acid (EAA) agonists, alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA), N-methyl-D-aspartic acid (NMDA) in 0 Mg2+, and L-glutamate. Each of these caused a depolarization of the cell membrane, a reduction in cell membrane resistance, and the onset of spontaneous firing. 3. Short-latency excitatory postsynaptic potentials (EPSPs) were evoked by stimulation of the lateral lemniscus in 77% of the neurons tested. The mean latency to initial depolarization was 0.9 ms. A single spike with relatively constant latency (mean 1.5 ms) was typically elicited when the strength of lemniscal stimulation was increased. A longer-latency EPSP (mean 2.9 ms) was seen in 34% of the neurons tested either with the slice in normal saline or after pharmacological block of the earlier, short-latency EPSP. The long-latency EPSP was followed by a single spike of multiple spikes with highly variable latencies (range 3.2-24 ms). In 28% of the neurons tested, both early and late EPSPs were observed in response to stimulation of a single location on the lateral lemniscus. 4. Stimulation of the commissure of Probst elicited short-latency EPSPs (mean 0.9 ms) in 37% of the neurons tested. Longer-latency EPSPs (mean 3.0 ms) were found in only 3% of the neurons in response to commissural stimulation. 5. The nonspecific EAA antagonist kynurenic acid blocked both short-and long-latency EPSPs evoked by either lemniscal or commissural stimulation. The non-NMDA antagonist 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX), at very low concentrations, blocked the short-latency EPSPs but had no effect on the longer-latency EPSPs. The short-latency EPSPs were unaffected by the NMDA antagonist D,L-2-amino-5-phosphonovaleric acid (APV). In contrast, the longer-latency EPSPs were blocked by APV, but never by CNQX. 6. DNLL neurons were affected by the inhibitory amino acid agonists gamma-aminobutyric acid (GABA) and glycine. The membrane resistance of the neurons was decreased by GABA and glycine in a solution of either normal or calcium-free saline in a concentration-dependent manner. 7. Inhibitory postsynaptic potentials (IPSPs) were elicited by stimulation of the lateral lemniscus in 53% of the neurons and the commissure of the Probst in 18% of the neurons tested. The mean latencies were 1.0 and 0.9 ms, respectively. The reversal potentials of the IPSPs were around -70 mV. 8. The IPSPs evoked by stimulation of the lateral lemniscus were blocked by the glycine receptor antagonist strychnine, but not by the GABA receptor antagonist bicuculline, whereas the IPSPs elicited by stimulation of the commissure of Probst were blocked by bicuculline but not strychnine.