Norepinephrine-induced potentiation is not blocked by the local diffusion of the NMDA channel blocker, ketamine, at concentrations that prevent tetanically-induced long-term potentiation in the dentate gyrus in vivo

Frizzell, Lynn Marie (1994) Norepinephrine-induced potentiation is not blocked by the local diffusion of the NMDA channel blocker, ketamine, at concentrations that prevent tetanically-induced long-term potentiation in the dentate gyrus in vivo. Masters thesis, Memorial University of Newfoundland.

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Abstract

An enduring increase in the size of the perforant path-evoked dentate gyrus response follows brief titanic stimulation. This Long-Tern Potentiation (LTP) is considered a cellular substrate of memory. A similar phenomenon, Norepinephrine-Induced Potentiation (NEP), results from exogenous application of NE or from endogenous NE release following Locus Coeruleus (LC) stimulation. It has been postulated that NE promotes LTP induction in a manner consistent with a role in arousal and attention. It has been documented both in vitro and in vivo that LTP induction requires the NMDA receptor and that NEP induction requires activation of the B-adrenergic receptor. In fact, it has been shown in the slice that LTP and NEP depend on both receptors. This suggests a codependence or synergy between NEP and LTP in the slice. However, the same has not been demonstrated in vivo. In fact, LTP is not eliminated by NE depletion in vivo, thus the B-receptor activation is probably not required. It was the aim of the present study to determine the role of the NMDA receptor in NEP in vivo. NEP was elicited by glutamate stimulation of the LC. Two recording pipettes were placed in the dentate gyrus. One pipette contained saline and the other, located less than 1mm away, contained the NMDA channel blocker, ketamine. Diffusion of ketamine significantly attenuated LTP as compared to that at the saline site. However, NEP was either unaffected or enhanced as compared to that at the saline site. NEP in vivo does not depend on the NMDA channel. B-receptor activation, and the cAMP-mediated biochemical cascade triggered, appears to be necessary and sufficient for the induction of NEP. If NE promotes attention and memory through the B-receptor in the dentate gyrus, it does so independently of the NMDA receptor.

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