Noradrenaline release from Locus Coeruleus terminals in the hippocampus enhances excitation-spike coupling in CA1 pyramidal neurons via β-adrenoceptors

Travis J Bacon, Anthony E Pickering, Jack R Mellor*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)

Abstract

Release of the neuromodulator noradrenaline signals salience during wakefulness, flagging novel or important experiences to reconfigure information processing and memory representations in the hippocampus. Noradrenaline is therefore expected to enhance hippocampal responses to synaptic input, however, noradrenergic agonists have been found to have mixed and sometimes contradictory effects on Schaffer collateral synapses and the resulting CA1 output. Here, we examine the effects of endogenous, optogenetically-driven noradrenaline release on synaptic transmission and spike output in mouse hippocampal CA1 pyramidal neurons. We show that endogenous noradrenaline release enhances the probability of CA1 pyramidal neuron spiking without altering feedforward excitatory or inhibitory synaptic inputs in the Schaffer collateral pathway. β-adrenoceptors mediate this enhancement of excitation-spike coupling by reducing the charge required to initiate action potentials, consistent with noradrenergic modulation of voltage-gated potassium channels. Furthermore, we find the likely effective concentration of endogenously released noradrenaline is sub micromolar. Surprisingly, although comparable concentrations of exogenous noradrenaline cause robust depression of slow afterhyperpolarisation currents, endogenous release of noradrenaline does not, indicating that endogenous noradrenaline release is targeted to specific cellular locations. These findings provide a mechanism by which targeted endogenous release of noradrenaline can enhance information transfer in the hippocampus in response to salient events.
Original languageEnglish
JournalCerebral Cortex
Publication statusAccepted/In press - 13 May 2020

Keywords

  • CA1
  • hippocampus
  • locus coeruleus
  • Noradrenaline
  • Synaptic transmission

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