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Non-associative hippocampal long-term depression (LTD) and associative neocortal long-term potentation of synaptic transmission in rat brain slices

Christofi, Gerolemos; (1993) Non-associative hippocampal long-term depression (LTD) and associative neocortal long-term potentation of synaptic transmission in rat brain slices. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

Long term potentiation (LTP) is an enduring, activity-dependent increase in synaptic transmission. Long term depression (LTD) is an enduring, activity-dependent decrease in synaptic transmission. Both phenomena may form the neuronal basis of learning and memory. Intracellular recording in isolated slices of rat brain was used to study (i) associative LTP in somatosensory neocortex, and (ii) non-associative LTD in hippocampus. (i) In layer V cells of neocortex, the incidence of induction of associative LTP was much lower in the slice than reported for the awake cat; this might be explained by the loss of extrinsic noradrenergic activity in the slice. To test this hypothesis, the actions of noradrenaline and the B1-adrenergic receptor agonist, isoprenaline, were investigated on (1) membrane properties, and (2) the probability of induction of associative LTP. The drugs produced a dose-dependent, reversible reduction of spike accommodation and an increase in excitability but had no effect on the depolarising slope or peak amplitude of subthreshold excitatory postsynaptic potentials (EPSPs) evoked by white matter stimulation. The probability of induction of associative LTP was not changed by these drugs, and hence the lower probability in vitro than in vivo cannot be explained solely by the loss of extrinsic noradrenergic activity. (ii) In hippocampal CA1 pyramidal neurones, postsynaptic potentials (PSPs) were evoked by test stimulation of stratum radiatum. Conditioning was non-associative and consisted of postsynaptic depolarization and firing, induced by either high frequency antidromic stimulation or postsynaptic injection of depolarizing current pulses. LTD was reliably induced postsynaptically when conditioning was applied during pharmacological block or reduction of synaptic transmission, achieved by transiently bathing slices in a bathing medium containing either a raised [Mg2+], selective glutamate antagonists, or a y-aminobutyric acid receptor antagonist. The postsynaptic induction of LTD required extracellular Ca2+. Measurements of resting and activity-dependent increases in cytosolic [Ca2+] were made using the fluorescent Ca2+ indicator FURA-2 iontophoresed into the cell to elucidate the conditions required for LTD induction. Possible reasons why the pharmacological reduction of synaptic transmission during conditioning stimuli could facilitate LTD induction are discussed.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Non-associative hippocampal long-term depression (LTD) and associative neocortal long-term potentation of synaptic transmission in rat brain slices
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Biological sciences; Long term potentiation; Long-term depression; Postsynaptic potentials
URI: https://discovery.ucl.ac.uk/id/eprint/10105860
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