The electrophysiological properties of dentate granule cells and hippocampal pyramidal neurons were examined with extracellular and intracellular recording techniques in the hippocampal slice.
Intracellular analysis revealed that there may exist two populations of granule cells distinguishable by the presence or absence of non-linear current-voltage (I-V) membrane properties (anomalous rectification, AR). The granule cells exhibiting AR also maintained greater resting membrane potentials and action potential (AP) amplitude values. The membrane input resistance (Rn) and time constant (Tc) measurements were similar between the populations in response to hyperpolarizing current injection, but granule cells displaying AR had significantly higher Rn and Tc values in response to depolarizing pulses. Both groups also responded to maintained depolarizing current injection with repetitive AP discharges; however, this response accommodated. Upon termination of the depolarizing current injection, an afterhyperpolarization (AHP) resulted, the amplitude of which appeared to depend on the duration of the depolarizing pulse and not on the number of APs generated during the pulse. Stimulation of either the lateral (LPP) or medial (MPP) perforant paths evoked a monosynaptic EPSP followed by a depolarizing afterpotential (DAP) and a long
afterhyperpolarization (LHP). In contrast, antidromic stimulation elicited a depolarizing-IPSP (D-IPSP) and a LHP. Both the DAP and D-IPSP were reversed by membrane depolarization, whereas, the LHP was inverted by membrane hyperpolarization. In all cases, however, the EPSP could not be inverted. Afterpotentials were associated with an increase in conductance, but the change accompanying the LHP was less than the DAP and D-IPSP. In addition, by reducing the [Ca]₀ and increasing the [Mg]₀, the DAP was attenuated and the LHP eliminated. Similar results were also obtained with the GABAB agonist, baclofen.
Paired pulse stimulation of either the LPP or MPP resulted in the potentiation of the intracellular EPSP at condition-test (C-T) intervals less than 100 ms; however, simultaneous extracellular records from the granule cell layer (GCL) illustrated depression of the EPSP. The discrepancy between the extra- and intracellular recordings was shown to be related to the presence of the DAP. In addition, the MPP evoked test EPSP at C-T intervals greater than 150 ms exhibited inhibition regardless of whether it was recorded inside or outside the granule cell and this EPSP depression was partially due to the granule cell LHP. The LPP evoked test EPSP potentiated at all C-T intervals less than 1s when recorded from the outer molecular layer (OML) but was inhibited at both the GCL and intracellular recording sites. These data confirmed that postsynaptic processes contribute to the short-term alterations observed with paired pulse stimulation.
The typical inhibition-potentiation-inhibition sequence of the perforant path (PP) evoked population spike (PS) was noted at C-T intervals of 20, 80 and 400 ms, respectively. The inhibition of the PS at 20 ms was abolished with perfusion of the GABA antagonist, bicuculline. In contrast, the PS inhibition at 400ms was unaffected by this treatment but was slightly attenuated by the gKca antagonist TEA. A number of factors appeared to contribute to the potentiation of the PS: 1) reduction in AP threshold; 2) the presence of the DAP; and 3) extrasynaptic events.
In addition to the PS data from normal tissue, hippocampal slices from chronically kindled rats exhibited depression of the PS at all C-T intervals tested. This augmentation of inhibition was dependent on the presence of hippocampal afterdischarges but not on motor seizures. Perfusing the kindled slices with either bicuculline or lowered [Cl]₀ did not markedly reverse the enhanced inhibition at C-T intervals which displayed dramatic facilitation in normal slices. Intracellular recordings of granule cells obtained from kindled slices also exhibited an increase in the Rn and Tc. Both the alterations in inhibition and membrane characteristics appear to be localized to.the granule cells, since these changes were not observed in CA1 pyramidal neurons.
These data indicate that short-term and long-term alterations in granule cell neuronal excitability are partially due to changes in the postsynaptic membrane. / Medicine, Faculty of / Cellular and Physiological Sciences, Department of / Graduate
| Identifer | oai:union.ndltd.org:UBC/oai:circle.library.ubc.ca:2429/27503 |
| Date | January 1986 |
| Creators | Oliver, Michael W. |
| Publisher | University of British Columbia |
| Source Sets | University of British Columbia |
| Language | English |
| Detected Language | English |
| Type | Text, Thesis/Dissertation |
| Rights | For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use. |
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