Dopaminergic neurons promote hippocampal reactivation and spatial memory persistence

McNamara, Colin G.; Tejero-Cantero, Álvaro; Trouche, Stéphanie; Campo-Urriza, Natalia; Dupret, David

doi:10.1038/nn.3843

Cited by 411 publications

(423 citation statements)

References 36 publications

(65 reference statements)

Supporting

Mentioning

357

Contrasting

Unclassified

Order By: Relevance

“…In this way, DA reduces interference from inputs arriving after a reward and increases the contrast between events taking place before and after reward, thereby virtually favoring the entrance of information temporally before reward into the hippocampus, be it a long time or shortly before reward. Complementing previous studies revealing that the midbrain DA system serves to stabilize the memory of events coincident with reward by promoting CA1 late LTP and network dynamics (10,11), the present study provides a mechanism by which information acquired before reward is encoded into memory more readily than information acquired after reward, particularly when the input and DA signal are temporally discontinuous.…”

Section: Discussionsupporting

confidence: 67%

“…In the hippocampus, a structure that is instrumental in forming memories of contexts and objects making up the experiences (5,6), DA must be present at the induction of long-term potentiation (LTP) to increase the magnitude of early-and late-phase LTP (7)(8)(9)(10). When released during learning, DA also has been found to enhance the reactivation of newly formed neural ensembles (11). The requisite coincidence between the DA signal and the conditioning stimulation may serve to ensure that only inputs concurrent with or occurring shortly before reward are encoded in long-term memory.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Dopaminergic inputs in the dentate gyrus direct the choice of memory encoding

Deng

Aimone

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Rewarding experiences are often well remembered, and such memory formation is known to be dependent on dopamine modulation of the neural substrates engaged in learning and memory; however, it is unknown how and where in the brain dopamine signals bias episodic memory toward preceding rather than subsequent events. Here we found that photostimulation of channelrhodopsin-2-expressing dopaminergic fibers in the dentate gyrus induced a long-term depression of cortical inputs, diminished theta oscillations, and impaired subsequent contextual learning. Computational modeling based on this dopamine modulation indicated an asymmetric association of events occurring before and after reward in memory tasks. In subsequent behavioral experiments, preexposure to a natural reward suppressed hippocampus-dependent memory formation, with an effective time window consistent with the duration of dopamine-induced changes of dentate activity. Overall, our results suggest a mechanism by which dopamine enables the hippocampus to encode memory with reduced interference from subsequent experience.T he brain structures crucial for memory formation are presumably under the control of the midbrain dopamine (DA) system, which selectively marks experiences that lead to reward (1, 2). In the striatum and the cortex, repetitive pairing of DA input after, but not before, sensorimotor stimulus within a narrow time window promotes structural and functional connectivity (3, 4), which may provide a cellular basis for reward to reinforce specifically an immediate past action. In the hippocampus, a structure that is instrumental in forming memories of contexts and objects making up the experiences (5, 6), DA must be present at the induction of long-term potentiation (LTP) to increase the magnitude of early-and late-phase LTP (7-10). When released during learning, DA also has been found to enhance the reactivation of newly formed neural ensembles (11). The requisite coincidence between the DA signal and the conditioning stimulation may serve to ensure that only inputs concurrent with or occurring shortly before reward are encoded in long-term memory. However, rewarding outcomes often may be delayed, and the involvement of the hippocampus is necessary when an event and its outcome are temporally discontinuous (12). This type of "memory" can be formed rapidly after even a single experience (5,6), and behavioral studies demonstrate that application of DA agonists in the hippocampus hours after training promotes memory maintenance (13,14), indicating that DA released from midbrain projections (Fig. S1) exerts distinct influences on the hippocampus to reinforce memory of earlier events selectively.Here we surveyed the dentate gyrus (DG) of the hippocampus to explore the possible sites and actions of DA. As the first stage of the intrahippocampal trisynaptic loop, the DG receives multiple processed sensory inputs from the entorhinal cortex (EC) and uses conjunctive encoding to integrate them for a memory representation (15). This region, together with area ...

show abstract

Section: Discussionsupporting

confidence: 67%

mentioning

confidence: 99%

Dopaminergic inputs in the dentate gyrus direct the choice of memory encoding

Deng

Aimone

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Moreover, generation of outcome predictions is proposed to rely on synaptic plasticity mechanisms boosted during slow-wave sleep (SWS) ). Thus, reward does not only support memory consolidation by increasing neuroplasticity in the hippocampus via dopamine release at encoding, but also by potentiating selective replay during sleep after encoding (Singer and Frank, 2009), recently confirmed also by optogenetic stimulation of mouse dopamine VTA-dorsal hippocampus pathway at encoding which enhanced spatial memory and increased reactivation of the stimulated neurons during sharp-wave ripples in post-encoding sleep (McNamara et al, 2014). In fact in humans, reward association or expectation has been shown to boost sleep-related gains in memory (Fischer and Born, 2009;Oudiette et al, 2013;Wilhelm et al, 2011;Igloi et al 2015).…”

Section: Box 2: Role Of Sleep In the Consolidation And Generalizationmentioning

confidence: 90%

Influence of reward motivation on human declarative memory

Miendlarzewska

Bavelier

Schwartz

2016

Neuroscience & Biobehavioral Reviews

149

134

View full text Add to dashboard Cite

a b s t r a c tMotivational relevance can prioritize information for memory encoding and consolidation based on reward value. In this review, we pinpoint the possible psychological and neural mechanisms by which reward promotes learning, from guiding attention to enhancing memory consolidation. We then discuss how reward value can spill-over from one conditioned stimulus to a non-conditioned stimulus. Such generalization can occur across perceptually similar items or through more complex relations, such as associative or logical inferences. Existing evidence suggests that the neurotransmitter dopamine boosts the formation of declarative memory for rewarded information and may also control the generalization of reward values. In particular, temporally-correlated activity in the hippocampus and in regions of the dopaminergic circuit may mediate value-based decisions and facilitate cross-item integration. Given the importance of generalization in learning, our review points to the need to study not only how reward affects later memory but how learned reward values may generalize to related representations and ultimately alter memory structure.

show abstract

“…However, in recent years, the source of dopamine in the dorsal hippocampus has become less clear. McNamara et al (12) argued that a dopaminergic projection from the VTA to the dorsal hippocampus promoted hippocampal reactivation during sleep and stabilized memory. However, only 10% of the sparse projection from the VTA to the hippocampus contains dopamine, raising the question of whether this weak VTA projection could be solely responsible for activating the dense network of dopamine receptors found in the dorsal hippocampus (13)(14)(15)(16).…”

mentioning

confidence: 99%

“…Taken together, there are some groups who argue that the VTA is the main source of dopamine to the dorsal hippocampus (12)(13)(14) and others who support the idea that dopamine is released from LC neurons (19)(20)(21). These conflicting hypotheses leave unanswered the question of which brain region supplies the dorsal hippocampus with dopaminergic tone.…”

mentioning

confidence: 99%

Dopamine release from the locus coeruleus to the dorsal hippocampus promotes spatial learning and memory

Kempadoo

Mosharov

Choi

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

494

507

View full text Add to dashboard Cite

Dopamine neurotransmission in the dorsal hippocampus is critical for a range of functions from spatial learning and synaptic plasticity to the deficits underlying psychiatric disorders such as attentiondeficit hyperactivity disorder. The ventral tegmental area (VTA) is the presumed source of dopamine in the dorsal hippocampus. However, there is a surprising scarcity of VTA dopamine axons in the dorsal hippocampus despite the dense network of dopamine receptors. We have explored this apparent paradox using optogenetic, biochemical, and behavioral approaches and found that dopaminergic axons and subsequent dopamine release in the dorsal hippocampus originate from neurons of the locus coeruleus (LC). Photostimulation of LC axons produced an increase in dopamine release in the dorsal hippocampus as revealed by high-performance liquid chromatography. Furthermore, optogenetically induced release of dopamine from the LC into the dorsal hippocampus enhanced selective attention and spatial object recognition via the dopamine D1/D5 receptor. These results suggest that spatial learning and memory are energized by the release of dopamine in the dorsal hippocampus from noradrenergic neurons of the LC. The present findings are critical for identifying the neural circuits that enable proper attention selection and successful learning and memory.dopamine | locus coeruleus | hippocampus | memory | attention D opamine is a neurotransmitter released throughout the brain to encode salience and facilitate the formation of associative memory (1, 2). When released into the dorsal hippocampus, dopamine binds to D1/D5 receptors to promote attention, episodic memory formation, spatial learning, and synaptic plasticity (3-5). Successful spatial learning requires that hippocampal place cells, location-encoding pyramidal neurons (6), display consistent and stable patterns of neural activity, a process that can be enhanced by selective attention to spatial cues and by dopamine agonists (7,8). Conversely, dopamine receptor blockade attenuates the ability of spatial attention to stabilize the firing pattern of hippocampal place cells (8). The role of dopamine in driving attentional processes is highlighted by the fact that methylphenidate, one of the most common treatments for attention-deficit hyperactivity disorder (ADHD), improves attention by increasing synaptic availability of dopamine in the hippocampus, as well as in the prefrontal cortex and striatum (9-11). These findings suggest that dopamine is critical for the selective attention underlying spatial learning and memory.For decades, the ventral tegmental area (VTA) has been the presumed source of hippocampal dopamine. However, in recent years, the source of dopamine in the dorsal hippocampus has become less clear. McNamara et al. (12) argued that a dopaminergic projection from the VTA to the dorsal hippocampus promoted hippocampal reactivation during sleep and stabilized memory. However, only 10% of the sparse projection from the VTA to the hippocampus contains dopamine, raising the...

show abstract

Dopaminergic neurons promote hippocampal reactivation and spatial memory persistence

Cited by 411 publications

References 36 publications

Dopaminergic inputs in the dentate gyrus direct the choice of memory encoding

Dopaminergic inputs in the dentate gyrus direct the choice of memory encoding

Influence of reward motivation on human declarative memory

Dopamine release from the locus coeruleus to the dorsal hippocampus promotes spatial learning and memory

Contact Info

Product

Resources

About