Intrinsically regulated learning is modulated by synaptic dopamine availability

Abstract

We recently provided evidence that an intrinsic reward-related signal-triggered by successful learning in absence of any external feedback-modulated the entrance of new information into long-term memory via the activation of the dopaminergic midbrain, hippocampus, and ventral striatum (the SN/VTA-Hippocampal loop; Ripollés et al., 2016).Here, we used a double-blind, within-subject randomized pharmacological intervention to test whether this learning process is indeed dopamine-dependent. A group of healthy individuals completed three behavioural sessions of our learning task after the intake of different pharmacological treatments: a dopaminergic precursor, a dopamine receptor antagonist or a placebo. Results show that the pharmacological intervention bidirectionally modulated behavioral measures of both learning and pleasantness, inducing memory benefits after 24 hours only for those participants with a high sensitivity to reward. These results provide causal evidence for a dopamine-dependent mechanism instrumental in intrinsically regulated learning, and further suggest that subject-specific dopamine sensitivity drastically alters learning success.

Prioritizing genes associated with brain disorders by leveraging enhancer-promoter interactions in diverse neural cells and tissues

“…While those shared associated genes of psychiatric disorders and behavioral-cognitive phenotypes show enriched biological functions of gene regulation, synaptic function, neuronal development (Fig. 5c), which is in line with the biological functions of synapses in the regulation of memory, perception, attention, and learning [114][115][116][117] and their established associations with complex psychiatric disorders [118,119]. Furthermore, we confirmed that the psychiatric disorders and behavioral-cognitive phenotypes showed more enrichment in synapse-associated processes than neurological disorders by using the SynGO annotations [120] (Additional file 1: Fig.…”

Memory modulations through musical pleasure

“…Follow-up studies also showed the implication of the reward-motivated learning system when participants successfully learned new information (i.e., pseudo-words), even when no external performance feedback was presented. 15 At the neural level, this is reflected by activations in the dopaminergic mesolimbic pathway (ventral tegmental area [VTA], VS, and NAcc), as well as in the hippocampus, the last one being crucial for long-term memory processes. More specifically, midbrain dopamine neurons in the VTA and their projections to the VS (NAcc) both support reward anticipation and modulate activity in the hippocampus.…”

“…More specifically, midbrain dopamine neurons in the VTA and their projections to the VS (NAcc) both support reward anticipation and modulate activity in the hippocampus. 15 According to the neo-Hebbian framework for episodic memory, 16 dopamine transmission in the mesolimbic system would promote memory formation and consolidation in the hippocampus by strengthening synaptic longterm potentiation. Therefore, all the stimuli triggering dopaminergic transmission in the hippocampus could result in long-term memory improvements, which can be also observed for events that occur after the dopamine release.…”

A cognitive neuroscience perspective on insight as a memory process: encoding the solution

“…The link between intrinsic reward learning and insight as sudden comprehension is further supported by fMRI studies from Ripollés et al (2016Ripollés et al ( , 2018. In a study on vocabulary learning, in which participants suddenly comprehended a word's meaning via inference from two sentences that contained it, Rippollés et al ( 2016) report pleasantness ratings during comprehension to correlate with later memory performance.…”

“…In the latter study, a correlation was observed with the re-solution effect (a special type of the generation effect referring to an advantage for solving repeatedly encountered problems, see Dominowski & Buyer, 2000) in behavioral memory performance. Dopamine is a neurotransmitter that plays an important role in reinforcement learning, and has been found to be released in VTA not only for external rewards, but also for novelty and intrinsic rewards (Kakade & Dayan, 2002;Ripollés et al, 2018;Schultz, 1998Schultz, , 2013. The amygdala, one of the core regions for processing emotion, has strong projections to the dopaminergic pathways.…”