Gatsby Computational Neuroscience Unit
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Supported by The Gatsby Foundation
Locus Coeruleus Norepinephrine and the Attention-Memory Continuum
Department of Psychology, Memorial University of Newfoundland, Canada
Three paradigms are described that, collectively, argue norepinephrine (NE) released by locus coeruleus (LC) activation operates to promote memory, as well as attention. The memory effects of NE are mediated through multiple mechanisms.
In the first paradigm attention is examined in rats in a holeboard. Here idazoxan increases focused attentional behavior as reported by Sara, possibly through enhanced LC bursts, while elevated tonic LC activation increases scanning measures of attention as reported by Geyer. These data are consistent with the bimodal role for LC in attention proposed by Aston-Jones.
In the second paradigm NE modulation of glutamatergic perforant path input to the dentate gyrus is evaluated using evoked potential recordings. A brief natural LC activation in the holeboard increases perforant path cell firing transiently, consistent with a brief enhancement of informational throughput. Glutamate infusion into LC produces more dramatic effects and appears to promote incorporation of new information into previously stable circuits. Glutamate LC activation transiently suppresses feed-forward inhibition, enhances theta frequencies and suppresses beta/gamma frequencies. More enduringly, such LC activation enhances cell firing in response to perforant path input and produces a delayed potentiation of synaptic input that requires protein synthesis. Exogenous NE measurements suggest higher levels of NE release are required for the enduring potentiation of perforant path transmission.
In the third paradigm NE operates as an unconditioned stimulus for odor preference learning in the rat pup. NE receptor activation has an inverted U curve relationship to preference learning. In this paradigm learning is related to the occurrence of cAMP waves suggesting an interaction between calcium and cAMP signaling in mediating memory-related cellular change. Decreasing cAMP breakdown enhances memory duration.