Oppositional and competitive instigation of hippocampal synaptic plasticity by the VTA and locus coeruleus.

The novelty, saliency, and valency of ongoing experiences potently influence the firing rate of the ventral tegmental area (VTA) and the locus coeruleus (LC). Associative experience, in turn, is recorded into memory by means of hippocampal synaptic plasticity that is regulated by noradrenaline sourced from the LC, and dopamine, sourced from both the VTA and LC. Two persistent forms of synaptic plasticity, long-term potentiation (LTP), and long-term depression (LTD) support the encoding of different kinds of spatial experience. To what extent the VTA and the LC influence the direction of change of synaptic plasticity and therefore the content of stored experience is not clear. Here, we report that test-pulse activation of Schaffer-collateral-CA1 synapses of freely behaving male rats, in conjunction with VTA stimulation, results in LTP (>24 h), whereas concomitant hippocampal afferent and LC stimulation results in LTD (>24 h). Effects are frequency-dependent (1 to 50 Hz) and competitive: high-frequency (25 Hz), but not low-frequency (5 Hz) optogenetic activation of tyrosine hydroxylase-positive (TH+) neurons in the VTA, results in D1/D5R-dependent LTP, whereas 5 Hz (but not 1, or 25 Hz) activation of TH+ neurons in the LC results in hippocampal LTD that is both D1/D5 and β-AR-dependent. These results suggest that the VTA and LC do not work in synergy, but rather function in a competing fashion to drive different forms of information encoding through synaptic plasticity. Our findings indicate that information transmitted by the VTA and LC is likely to play a decisive role in the shaping of hippocampal information storage and the nature of learned experience.