Excitatory and inhibitory synaptic currents and receptors in rat medial septal neurones.
1. A thin-slice preparation was used to study the postsynaptic potentials and the underlying currents of visually identified rat medial septal (MS) neurones under tight-seal voltage- and current-clamp conditions. 2. Upon stimulation of the afferent fibres, all MS neurones exhibited a sequence of excitatory-inhibitory postsynaptic potentials (EPSP-IPSP). Under voltage clamp, with potassium glutamate as internal solution and at negative holding potentials (Vh), this synaptic pattern appeared as an initial inward current followed by a longer lasting outward current. 3. The inward postsynaptic current was completely abolished by 5 microM-6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) whereas the outward current disappeared in the presence of 10 microM-bicuculline. Thus the major excitatory and inhibitory synaptic inputs were identified as being due to activation of quisqualate/kainate glutamatergic and gamma-aminobutyric acid (GABAA) receptors, respectively. 4. At positive Vh a CNQX-resistant component of the excitatory postsynaptic current (EPSC) was revealed. This component was slower than the one mediated by the quisqualate receptor and was abolished by 3-3(2-carboxypiperazine-4-yl)propyl-1-phosphonate (CPP), indicating that N-methyl-D-aspartate (NMDA) receptors are involved in excitatory synaptic transmission in MS cells. The existence of the two main subtypes (NMDA and non-NMDA) of glutamatergic receptors in MS neurones was also confirmed by the responses of the neurones to bath application of the different agonists (glutamate, quisqualate, kainate and NMDA). 5. The CNQX-sensitive EPSC had a reversal potential near 0 mV. The fast rise time (approximately 0.7 ms) indicates a somatic location of the excitatory synapses. The relaxation kinetics of the fast EPSC were fitted by a single exponential function with a time constant of 1.13 +/- 0.1 ms. This parameter was independent of Vh. Fast EPSCs were blocked by CNQX in a dose-dependent manner (dissociation constant, KD = 0.2 microM). 6. Inhibitory postsynaptic currents (IPSCs) were studied in symmetrical chloride solutions after blockade of the excitatory receptors. The current-voltage relation was linear and reversed at 0 mV. The IPSCs had a fast rise time and their decay was best fitted by the sum of two exponentials with time constant of approximately 20 and 50 ms (Vh = -60 mV). The IPSCs were abolished by bicuculline (KD = 1 microM), a selective antagonist of GABAA receptors. As expected, bath application of GABA produced large whole-cell currents. 7. In many cells, in addition to the usual EPSP-IPSP sequence, failures of either the EPSP or the IPSP were frequently observed during the experimental protocol.(ABSTRACT TRUNCATED AT 400 WORDS)
Schneggenburger
R
R
Max-Planck Institut für biophysikalische Chemie, Göttingen, Germany.
López-Barneo
J
J
Konnerth
A
A
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D004558:Electric Stimulation; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D017981:Receptors, Neurotransmitter / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D013570:Synaptic Membranes / Q000187:drug effects
D005971:Glutamates; D011810:Quinoxalines; D017981:Receptors, Neurotransmitter; D018698:Glutamic Acid; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione