The Three Faces of Norepinephrine: Plasticity at the Perforant Path- Dentate Gyrus Synapse

John Sarvey and his collaborators made major contributions to our understanding of the noradrenergic contribution to plasticity in the dentate gyrus of the hippocampus. The present chapter considers, first, the conclusions reached using in vitro models, and is based primarily on the work of John Sarvey and his collaborators, and, then, describes in vivo data and the interrelationships between the two approaches. These considerations lead us to the proposal that norepinephrine (NE) mediates three distinct forms of plasticity: immediate increases in cell excitability (i.e., likelihood of cell firing to a given synaptic input), immediate increases in synaptic strength and delayed increases in synaptic strength. All of these changes could contribute to the enduring functional alteration of information flow in the dentate gyrus and, thus, could act as memory mechanisms. A decade after the first report of tetanic stimulation-induced homosynaptic (i.e., presumed glutamate-mediated modulation at glutamate synapses) long-term potentiation (LTP) of the perforant path evoked potential in the dentate gyrus in vivo (Bliss and Gardner-Medwin, 1973; Bliss and Lomo, 1973), we observed that iontophoretic application of NE in the dentate gyrus could induce a potentiation of the perforant path evoked population spike that greatly outlasted the 15 min iontophoresis period (Neuman and Harley, 1983). In -40% of the experiments population spike potentiation lasted more than 30 min, an accepted criterion for LTP at that time. Potentiation in one rat was monitored for 11 hours. These observations were christened NE-induced long-lasting potentiation to distinguish the phenomenon from the earlier homosynaptic LTP. The heterosynaptic (i.e., NE-activation modulating a glutamate-mediated response) modulation of glutamate synapses by NE in the perforant path of the dentate gyrus did not require high frequency electrical input, and suggested that the co-activation of