An Investigation of Paired Pulse Interactions Between Evoked Field Potentials in Normal and Bicuculline-Superfused Rat Hippocampal Slices

Higgins, Michael Joseph (1996) An Investigation of Paired Pulse Interactions Between Evoked Field Potentials in Normal and Bicuculline-Superfused Rat Hippocampal Slices. PhD thesis, University of Glasgow.

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1. This thesis is concerned with the investigation of interactions which can be demonstrated in the CA1 area of the hippocampal slice between pairs of evoked field potentials recorded extracellularly in the stratum pyramidale. 2. Paired-pulse inhibition and paired-pulse facilitation of orthodromic population spikes by a previous conditioning stimulus were readily demonstrated using a single stimulating electrode placed in the stratum radiatum. As described by other investigators, the nature of the interaction observed depended on the interstimulus interval between test and conditioning stimuli. Inhibition predominated at short interstimulus intervals, changing to facilitation as the interstimulus interval was increased. Decreasing the strength of the conditioning stimulus increased the magnitude of the paired-pulse inhibition or changed facilitation to inhibition. 3. When the GABA-A antagonist bicuculline was added to the superfusate the single population spike normally recorded in the stratum pyramidale in response to a single stimulus in the stratum radiatum became a short burst of spikes up to 40 ms long. Under these conditions of background pyramidal cell disinhibition, using a single stimulating electrode in the stratum radiatum and a conditioning stimulus that was supramaximal for the size of the evoked potential, a consistent pattern of paired-pulse interactions was observed. Two temporally distinct phases of paired-pulse inhibition were seen, at short (< 50 ms) and at intermediate (200 to 500 ms) interstimulus intervals. At an interstimulus interval of 100 ms inhibition either showed a marked minimum or facilitation was seen. At interstimulus intervals longer than 900 ms there was a second phase of facilitation. 4. At interstimulus intervals less than 50 ms and between 300 and 900 ms, 10 muM bicuculline significantly increased inhibition or decreased facilitation compared with drug-free control in the same slices. However when the interstimulus interval was 100 ms the slices showed significantly increased facilitation in the presence of bicuculline. 5. During bicuculline superfusion, as in the bicuculline-free slice, decreasing the strength of the conditioning stimulus increased the magnitude of the paired-pulse inhibition or changed facilitation to inhibition. 6. The medium-latency (interstimulus interval of 300 ms) bicuculline-enhanced paired-pulse inhibition was decreased by the GABA-B antagonist 2-hydroxysaclofen, and by the GABA-B agonist baclofen, strongly suggesting that it was at least partly mediated by GABA released from interneurones and acting at GABA-B receptors. 7. Experiments using antidromic test stimuli to determine whether the relevant GABA-B receptors were presynaptic on the Schaffer collateral terminals or postsynaptic on the pyramidal cells were inconclusive. 8. Several lines of evidence suggested that there is an additional postsynaptic component to the medium-latency bicuculline-enhanced paired-pulse inhibition which is not GABA-mediated and is probably related directly to the recurrent tiring of the pyramidal cells. In particular, during bicuculline superfusion, the addition of baclofen or 2-hydroxysaclofen had no effect on the paired-pulse inhibition of antidromic test potentials by orthodromic conditioning potentials. Furthermore, a similar paired-pulse inhibition was demonstrated between antidromic potentials in nominally CA1cium-free superfusate in the absence of added agents. 9. Adenosine decreased medium-latency bicuculline-enhanced paired- pulse inhibition of orthodromic test potentials in that paired-pulse inhibition in the presence of adenosine was less than for nonadenosine superfused control potentials of the same size. In addition, adenosine inhibited the conditioned potential, which is already reduced by paired-pulse inhibition, significantly less than a matched unpaired potential. The validity of this conclusion was further supported by simple computer modelling of the effects of evoked potential size on susceptibility to inhibition. 10. A comparison was made of the concentration-response relationships for the effects of adenosine to reduce paired-pulse inhibition and to reduce the size of single evoked potentials. The experiment was carried out both during bicuculline superfusion and in the absence of bicuculline. The results ruled out the possibility that the effect of adenosine on paired-pulse inhibition was caused by the different sensitivity of two populations of adenosine receptors, those on excitatory terminals to interneurones and those on excitatory terminals to the pyramidal cells. 11.Adenosine was less effective at reducing bicuculline-enhanced paired-pulse inhibition when the conditioning stimulus was supramaximal at 1 mA. 12.These findings are all compatible with the effect of adenosine to reduce bicuculline-enhanced paired-pulse inhibition being mediated by an increase in simultaneous paired-pulse facilitation. There is some difficulty however in integrating this explanation with the residual CA1cium theory of paired-pulse facilitation.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Additional Information: Adviser: Trevor W Stone
Keywords: Pharmacology, Neurosciences
Date of Award: 1996
Depositing User: Enlighten Team
Unique ID: glathesis:1996-74916
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 27 Sep 2019 15:12
Last Modified: 27 Sep 2019 15:12

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