Noradrenaline blocks accommodation of pyramidal cell discharge in the hippocampus

The hippocampus, as well as a variety of other brain regions, is known to receive a diffuse projection of noradrenaline (NA) containing fibres which originates in the brain stem 1–4 . Although there is considerable evidence for the involvement of this system in a variety of behaviours 5–7 , the precise cellular actions of NA are poorly understood. Early studies emphasized the direct inhibitory effects of NA 8–12 ; more recent experiments have shown that at several sites, NA, or stimulation of NA-containing afferents, can also facilitate excitatory synaptic responses 13–18 . This has led to the concept that NA increases the ‘signal-to-noise’ ratio of neurones 13 , acting as an ‘enabling’ device 4 which allows cells to respond more briskly to conventional synaptic excitation. In the olfactory bulb, NA reduces inhibitory postsyn-aptic potentials by a presynaptic action 19 , which could contribute to enhanced excitatory synaptic responses. However, in other systems, NA has been reported to enhance excitatory responses to iontophoretically applied transmitters, and it was proposed that NA increases the sensitivity of the neurone to these excitatory transmitters 13–15 . We report here experiments that could explain such direct effects. We have found that NA and cyclic AMP block the Ca 2+ -activated K + conductance in hippocampal pyramidal cells and that this blockade occurs at a step subsequent to the entry of Ca 2+ into the neurone. As a consequence, the spike frequency adaptation or accommodation which normally occurs with depolarizing stimuli is severely reduced. Thus, NA greatly increases the number of spikes elicited by a depolarizing stimulus.