Distinct Roles of Dopamine and Noradrenaline in Incidental Memory - PubMed (original) (raw)

Randomized Controlled Trial

Distinct Roles of Dopamine and Noradrenaline in Incidental Memory

Tobias U Hauser et al. J Neurosci. 2019.

Abstract

Episodic memory is sensitive to the influence of neuromodulators, such as dopamine and noradrenaline. These influences are considered important in the expression of several known memory biases, though their specific role in memory remains unclear. Using pharmacological agents with relatively high selectivity for either dopamine (400 mg amisulpride) or noradrenaline (40 mg propranolol) we examined their specific contribution to incidental memory. In a double-blind placebo-controlled human study (30 females, 30 males in total), we show that a memory selectivity bias was insensitive to propranolol but sensitive to amisulpride, consistent with a dominant influence from dopamine. By contrast, a putative arousal-induced memory boosting effect was insensitive to amisulpride but was sensitive to propranolol, consistent with a dominant noradrenaline effect. Thus, our findings highlight specific functional roles for dopamine and noradrenaline neurotransmission in the expression of incidental memory.SIGNIFICANCE STATEMENT Why some information is preferentially encoded into memory while other information is not is a central question in cognitive neuroscience. The neurotransmitters dopamine and noradrenaline are often assumed critical in influencing this selectivity, but their specific contributions remain obscure. In this double-blind, placebo-controlled, between-subjects drug study, we investigate the contributions of noradrenaline and dopamine to episodic memory. Using an incidental memory task, we find that blocking dopamine (400 mg amisulpride) eliminates a neural-gain related memory selectivity bias. Blocking noradrenaline function (40 mg propranolol), in contrast, abolishes an arousal-related memory enhancement. In this assessment of dopamine and noradrenaline neuromodulatory effects we reveal their specific contributions to episodic memory.

Copyright © 2019 Hauser et al.

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Figures

Figure 1.

Figure 1.

Neural gain during incidental episodic memory. a, To assess specific effects of dopamine and noradrenaline, we administered either amisulpride or propranolol before an incidental learning task in a placebo-controlled design. Subjects were probed with a recognition task (c) ∼20 min after performing an incidental-learning task (b). b, Incidental learning phase: subjects rated readability of common words, presented in two different fonts. Twenty-five percent of the words were randomly rewarded £0.50 to boost arousal (“50 p” or “00 p” feedback after word presentation). c, Memory recognition test: subjects were asked to indicate whether a word has been shown during the first phase. Half of the words were presented in a different font compared with the original presentation (switch-font condition). d, Predictions of neural gain. Neural gain is assumed to modulate how information is processed along neural populations. Under high neural gain (black), relevant features (such as the word shape in our experiment) are prioritized and their representation strengthened while unimportant features (here: word meaning) will be suppressed. Under low neural gain (gray), both relevant and negligible features are represented increasing the likelihood that both word shape and semantics will be stored in memory. e, Pupil response indicates neural gain effects. Across all groups, we replicate our previous finding that pupil response during learning (as indirect indicator of neural gain) is linked to memory performance. Subjects with low pupil response (indicating high gain) show a stronger memory selectivity bias with a worse performance after a font switch (compared with a presentation in the same font; measured by hit rate). Subjects with larger phasic pupil response (indicating low gain) show less memory bias between same and switch-font condition. Shaded area in a: time period of likely drug effect. inf, Unlimited response time; ○, placebo, +, propranolol, *, amisulpride.

Figure 2.

Figure 2.

Blocking dopamine functioning reduces memory selectivity effect. Subjects generally show decreased recognition memory performance when words are probed in a different compared with the original font. However, this effect is only present in subjects under placebo and noradrenaline blockade (propranolol). Blocking of dopamine functioning (amisulpride) abolished the font switching effect, without impairing overall recognition performance. The findings indicate that this, neural gain-related memory selectivity bias is sensitive to dopamine but not noradrenaline function. Error bar: ± 1 S.E.M., ***p ≤ 0.001, **p < 0.01; n.s., _p_ > 0.10.

Figure 3.

Figure 3.

Implicit arousal-related memory boost eliminated by noradrenaline blockade. a, Rare performance-independent rewards led to increased arousal as measured by a larger pupil dilation after rewarded (compared with non-rewarded) trials. The effect arose ∼2 s after reward presentation in all groups (horizontal lines: cluster-level significant group effects p < 0.05 using permutation tests). **_b_**, The arousal-related rewards immediately following word presentation during incidental memory phase led to improved subsequent recognition. This effect was present both after placebo and dopamine blockade, but not after noradrenaline blockade. **_c_**, The arousal-induced memory boost was not explicit. When subjects were asked to explicitly indicate which words were rewarded (source memory task), they did not perform above chance (dashed line) and the groups did not differ in their performance. Our findings suggest that the implicit arousal-induced memory boost primarily depends on β-adrenoceptor functioning. n.s., _p_ > 0.05, *p < 0.05.

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