Brain Research, 558 (1991) 120-122 © 1991 Elsevier Science Publishers B.V. All fights reserved. 0006-8993/91/$03.50 ADONIS 000689939124814X
120
BRES 24814
Long-term potentiation of excitatory and slow inhibitory synaptic potentials in the hippocampal-septal projection of the rat David R. Stevens and Carl W. Cotman Department of Psychobiology, University of California, Irvine, CA 92717 (U.S.A.)
(Accepted 28 May 1991) Key words: Long-term potentiation; N-Methyl-D-aspartate;Septum; Excitatory postsynaptic potential; Inhibitory postsynaptic potential
The hippocampal projection to the lateral septum was examined for use-dependent plasticity in a brain slice preparation using intracellular recording. Paired-pulse facilitation and posttetanic potentiation were present. Long-term potentiation (LTP) following high-frequency stimulation was observed after treatment with the GABAA antagonist bicuculline. A slow inhibitory synaptic potential also exhibited long-lasting potentiation after high-frequency stimulation. LTP of both components of the response was sensitive to NMDA antagonists. One of the major efferent pathways of the hippocampus enters the lateral septum s. This projection originates from collateral fibers of CA3 neurons which also contribute to the Schaffer collateral/commissural projection 12. Thus the Schaffer collateral/commissural and septal projections of area CA3 provide a situation in which it is possible to compare the postsynaptic actions of transmitter released from the same neurons onto different neuronal target populations. The postsynaptic pharmacology of the hippocampalseptal projection is similar to that of the Schaffer collateral synapse 9. Previously, we have shown that stimulation of the fimbria gives rise to excitatory postsynaptic potentials in the septum that are blocked by antagonists of excitatory amino acid receptors 9. Antagonists specific to N-methyl-D-aspartate (NMDA) receptors have little affect on the EPSP. Thus, N M D A receptors do not appear to play a part in normal transmission in this pathway 9, although under certain conditions N M D A receptors can contribute to synaptic transmission at this synapse 7. N M D A and non-NMDA excitatory amino acid receptors are present on the principal neurons and the inhibitory interneurons of the lateral septum 6. We have examined the use-dependent plasticity of the hippocampal-septal synapse in an in vitro rat brain slice preparation in order to determine if such plasticity is present in the septum and if N M D A receptors in this area play a role in potentiation of synaptic transmission as they do in the Schaffer collateral pathway 4'5.
Male Sprague-Dawley rats weighing 160-250 g were decapitated with a guillotine, and transverse slices (500 a m thick) containing the medial and lateral septum were prepared with methodology described previously 1°. Two to 3 slices prepared in this manner contain a segment of the fimbria that can be stimulated to produce monosynaptic excitatory postsynaptic potentials (EPSP). A bipolar stimulating electrode was placed at the distal end of the fimbria and monopolar square current pulses with a duration of 500 #s were delivered. The amplitude and polarity of the pulses were adjusted such that minimal current was required to elicit EPSPs. Intracellular recordings were made in the dorsolateral septum using glass microelectrodes pulled from standardwall fiber-filled borosilicate glass. Recording electrodes were filled with 2 M potassium acetate and had resistances in the range of 70 to 120 MI2. The signals were recorded with a bridge-type amplifier and were stored on FM tape and on a chart recorder. Portions of the records were digitized and stored on disk for offline analysis. Digital averages of 10 consecutive EPSPs were used for comparison of control and treatment responses. Changes in amplitude and rate of rise of EPSPs were examined following pairs and trains of stimuli. The slices were submerged and superfused in artificial cerebrospinal fluid (ACSF) of the following composition (in mM): NaCI 117, KCI 2.5, CaCI 2 2.0, K2HPO 4 1.2, MgSO 4 2.0, N a H C O 3 25, D-glucose 10.0. The ACSF was continuously bubbled with 95% 0 2 - 5 % CO 2 to maintain pH and was maintained at 33 + 1 °C. Pharmacological
Correspondence: D.R. Stevens, 940 Belmont St., Neuroscience Laboratory 151C, Harvard Medical School/VAMC, Brockton, MA 02401, U.S.A.
121 2.5
2.2 pD
._J "~
120
BRES 24814
Long-term potentiation of excitatory and slow inhibitory synaptic potentials in the hippocampal-septal projection of the rat David R. Stevens and Carl W. Cotman Department of Psychobiology, University of California, Irvine, CA 92717 (U.S.A.)
(Accepted 28 May 1991) Key words: Long-term potentiation; N-Methyl-D-aspartate;Septum; Excitatory postsynaptic potential; Inhibitory postsynaptic potential
The hippocampal projection to the lateral septum was examined for use-dependent plasticity in a brain slice preparation using intracellular recording. Paired-pulse facilitation and posttetanic potentiation were present. Long-term potentiation (LTP) following high-frequency stimulation was observed after treatment with the GABAA antagonist bicuculline. A slow inhibitory synaptic potential also exhibited long-lasting potentiation after high-frequency stimulation. LTP of both components of the response was sensitive to NMDA antagonists. One of the major efferent pathways of the hippocampus enters the lateral septum s. This projection originates from collateral fibers of CA3 neurons which also contribute to the Schaffer collateral/commissural projection 12. Thus the Schaffer collateral/commissural and septal projections of area CA3 provide a situation in which it is possible to compare the postsynaptic actions of transmitter released from the same neurons onto different neuronal target populations. The postsynaptic pharmacology of the hippocampalseptal projection is similar to that of the Schaffer collateral synapse 9. Previously, we have shown that stimulation of the fimbria gives rise to excitatory postsynaptic potentials in the septum that are blocked by antagonists of excitatory amino acid receptors 9. Antagonists specific to N-methyl-D-aspartate (NMDA) receptors have little affect on the EPSP. Thus, N M D A receptors do not appear to play a part in normal transmission in this pathway 9, although under certain conditions N M D A receptors can contribute to synaptic transmission at this synapse 7. N M D A and non-NMDA excitatory amino acid receptors are present on the principal neurons and the inhibitory interneurons of the lateral septum 6. We have examined the use-dependent plasticity of the hippocampal-septal synapse in an in vitro rat brain slice preparation in order to determine if such plasticity is present in the septum and if N M D A receptors in this area play a role in potentiation of synaptic transmission as they do in the Schaffer collateral pathway 4'5.
Male Sprague-Dawley rats weighing 160-250 g were decapitated with a guillotine, and transverse slices (500 a m thick) containing the medial and lateral septum were prepared with methodology described previously 1°. Two to 3 slices prepared in this manner contain a segment of the fimbria that can be stimulated to produce monosynaptic excitatory postsynaptic potentials (EPSP). A bipolar stimulating electrode was placed at the distal end of the fimbria and monopolar square current pulses with a duration of 500 #s were delivered. The amplitude and polarity of the pulses were adjusted such that minimal current was required to elicit EPSPs. Intracellular recordings were made in the dorsolateral septum using glass microelectrodes pulled from standardwall fiber-filled borosilicate glass. Recording electrodes were filled with 2 M potassium acetate and had resistances in the range of 70 to 120 MI2. The signals were recorded with a bridge-type amplifier and were stored on FM tape and on a chart recorder. Portions of the records were digitized and stored on disk for offline analysis. Digital averages of 10 consecutive EPSPs were used for comparison of control and treatment responses. Changes in amplitude and rate of rise of EPSPs were examined following pairs and trains of stimuli. The slices were submerged and superfused in artificial cerebrospinal fluid (ACSF) of the following composition (in mM): NaCI 117, KCI 2.5, CaCI 2 2.0, K2HPO 4 1.2, MgSO 4 2.0, N a H C O 3 25, D-glucose 10.0. The ACSF was continuously bubbled with 95% 0 2 - 5 % CO 2 to maintain pH and was maintained at 33 + 1 °C. Pharmacological
Correspondence: D.R. Stevens, 940 Belmont St., Neuroscience Laboratory 151C, Harvard Medical School/VAMC, Brockton, MA 02401, U.S.A.
121 2.5
2.2 pD
._J "~
