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Associative induction of short-term potentiation in rat hippocampus

University of British Columbia

Tetanic stimulation of excitatory afferent pathways in the hippocampus can lead to long-term potentiation (LTP) of the postsynaptic response. Simultaneous tetanization of two separate but convergent afferent pathways can result in associative LTP, which exhibits a magnitude that is greater than the sum of the individual potentiations. Short-term potentiation (STP) of synaptic transmission also occurs in the tetanized pathway, and is a well known presynaptic phenomenon at other neuronal junctions. Studies were conducted to examine if STP in the hippocampus could be induced associatively and to determine the nature of pre- and postsynaptic interactions leading to this associative potentiation. Experiments were conducted on transversely sectioned rat hippocampal slices maintained in vitro. Population responses were recorded from the CA[sub 1b] pyramidal cells and were evoked using stimulating electrodes placed in stratum radiatum, stratum oriens and the alveus. Population excitatory postsynaptic potentials (EPSP) were recorded with extracellular recording electrodes placed at the apical dendrites of the CA₁ cells. Individual cellular EPSPs were recorded from the CA₁cell somata. To assess the influence of tetanic conditioning on an untetanized afferent pathway, stimulating electrodes were placed in different pathways to deliver tetanic conditioning stimulation to the CA₁ cells. Another stimulating electrode was placed in a separate test pathway, which also converged on the same population of CA₁ cells. The test pathway either remained unstimulated or was stimulated once in conjunction with each tetanic conditioning train of stimulation. Conditioning tetani delivered through strata oriens or radiatum induced associative STP of the test response when paired with a single test stimulation, but caused depression of the response when unpaired. Antidromic tetanization of CA₁ cells at the alveus or a depolarization of these cells by intracellular current injections produced the same pattern of potentiation with the paired/unpaired paradigm. By delivering a number of these paired test-plus-conditioning trains in rapid succession, the magnitude of the STP increased in a graded manner, and the size and time course resembled those of STP found at other junctions. At the maximum of ten pairings used in these studies, the evoked associative STP was succeeded by LTP. Presynaptic excitability changes were assessed by monitoring the amount of current needed to fire an antidromic action potential from the Schaffer collateral terminals. These are the afferent terminals that form en passant synapses with the apical dendrites of the CA₁ cells. Pairing a single stimulation of these terminals with a conditioning tetanus of other afferents resulted in STP of the test EPSP, as well as a parallel decrease in the test afferent terminal excitability. These changes are in accord with a presynaptic mechanism of STP found in the spinal cord and neuromuscular junction. The temporal overlap between the single test afferent volley and the conditioning tetanus was found to be a determinant both of the magnitude and the probability of STP induction. The single test volley could precede the conditioning tetanus by up to 50 msec or follow the tetanus by up to 80 msec and still induce a degree of STP. However, the greatest amount of STP was produced by simultaneous test and conditioning stimulations. Theselenient temporal limits suggest an altered excitability state due to pre-and postsynaptic interactions. Taken- together, the evidence indicates a postsynaptic initiating site for associative STP and LTP in the hippocampus. The initial postsynaptic depolarization appeared to interact with an afferent volley to alter presynaptic terminal excitability. It is proposed that a subliminal presynaptic release process follows an action potential in the terminal. This subliminal process may be facilitated by associative interactions between the postsynaptic depolarization and an action potential in the presynaptic terminal through an altered presynaptic terminal excitability. The associative interactions could lead to enhanced transmitter release by subsequent afferent volleys. The nature of this subliminal process is unknown, but several hypotheses were discussed. It was concluded that associative potentiation has a presynaptic locus of maintenance, and that STP and LTP in the hippocampus may be simply different multiples of the same unit potentiation event. However, the results do not rule out a possible additional postsynaptic locus for the maintenance of STP and LTP.

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2010-06-19

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http://hdl.handle.net/2429/25841

Pharmacology

University of British Columbia

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