Norepinephrine and the dentate gyrus

Harley, Carolyn W.

doi:10.1016/s0079-6123(07)63018-0

Cited by 123 publications

(96 citation statements)

References 151 publications

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“…It is thus possible that some ChR2-expressing fibers in the DG originated from noradrenergic nuclei in a TH-Cre;Ai27 mouse model. However, in line with most studies (28), norepinephrine (NE) potentiated GC responses elicited by PP stimulation, an effect opposite that of DA (Fig. S3A).…”

Section: Significancesupporting

confidence: 87%

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

Deng

Aimone

et al. 2016

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

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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 ...

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Section: Significancesupporting

confidence: 87%

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

Deng

Aimone

et al. 2016

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

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“…It is therefore possible that the overgeneralization of memory representations that results in a positive response bias is caused by stress-induced tonic activation of this circuit. Yet, memory accuracy for such generalized memory traces could still be preserved under these circumstances because elevated levels of catecholamines and glucocorticoids may generally enhance neural plasticity during encoding (Lisman and Grace, 2005;Harley, 2007) and postencoding consolidation (Joëls et al, 2006;Sara, 2009). Although future research using, for instance, pharmacological manipulations will be necessary to provide more definite answers, our findings suggest that changes in catecholaminergic signaling may play a key role in altering memory formation under stress.…”

Section: Discussionmentioning

confidence: 84%

“…Intermediate levels of catecholamines are thought to represent an optimal state characterized by selective phasic firing patterns in response to novel and/or salient stimuli. Through such phasic signaling, the hippocampus forms a functional loop with neuromodulatory midbrain nuclei that determines selective processing of novel information and entry into long-term memory (Lisman and Grace, 2005;Harley, 2007). Specifically, novelty signals generated in the hippocampus (Fernández and Tendolkar, 2006) may trigger phasic catecholaminergic activity in neuromodulatory midbrain nuclei, which in turn enhances hippocampal neuroplasticity (Lisman and Grace, 2005;Sara, 2009).…”

Section: Discussionmentioning

confidence: 99%

Understanding Low Reliability of Memories for Neutral Information Encoded under Stress: Alterations in Memory-Related Activation in the Hippocampus and Midbrain

Qin¹,

Hermans²,

Marle³

et al. 2012

J. Neurosci.

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Exposure to an acute stressor can lead to unreliable remembrance of intrinsically neutral information, as exemplified by low reliability of eyewitness memories, which stands in contrast with enhanced memory for the stressful incident itself. Stress-sensitive neuromodulators (e.g., catecholamines) are believed to cause this low reliability by altering neurocognitive processes underlying memory formation. Using event-related functional magnetic resonance imaging, we investigated neural activity during memory formation in 44 young, healthy human participants while incidentally encoding emotionally neutral, complex scenes embedded in either a stressful or neutral context. We recorded event-related pupil dilation responses as an indirect index of phasic noradrenergic activity. Autonomic, endocrine, and psychological measures were acquired to validate stress manipulation. Acute stress during encoding led to a more liberal response bias (more hits and false alarms) when testing memory for the scenes 24 h later. The strength of this bias correlated negatively with pupil dilation responses and positively with stress-induced heart rate increases at encoding. Acute stress, moreover, reduced subsequent memory effects (SMEs; items later remembered vs forgotten) in hippocampus and midbrain, and in pupil dilation responses. The diminished SMEs indicate reduced selectivity and specificity in mnemonic processing during memory formation. This is in line with a model in which stress-induced catecholaminergic hyperactivation alters phasic neuromodulatory signaling in memory-related circuits, resulting in generalized (gist-based) processing at the cost of specificity. Thus, one may speculate that loss of specificity may yield less discrete memory representations at time of encoding, thereby causing a more liberal response bias when probing these memories.

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“…The LC densely innervates limbic structures involved in consolidation of long-term memory, including the hippocampus and amygdala (Sara 2009). Noradrenergic projections have been indicated to modulate hippocampal synaptic plasticity (Neuman and Harley 1983;Harley 2007) and exerts influence on memory consolidation (Mueller and Cahill 2010;McIntyre et al 2012) and reconsolidation (Debiec and LeDoux 2004) through binding of noradrenalin to b-adrenergic receptors within the BLA and hippocampus. Furthermore, the a2 adrenoreceptor antagonist yohimbine, which enhances noradrenalin release and increases sympathetic activity, has been shown to evoke panic attacks and anxiety, but also to enhance extinction of conditioned fear (Cain et al 2004).…”

Section: Discussionmentioning

confidence: 99%

A bout of voluntary running enhances context conditioned fear, its extinction, and its reconsolidation

2014

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Three experiments used rats to examine the effect of a single bout of voluntary activity (wheel running) on the acquisition, extinction, and reconsolidation of context conditioned fear. In Experiment 1, rats provided with access to a wheel for 3 h immediately before or after a shocked exposure to a context froze more when tested in that context than rats provided with access to the wheels 6 h after the shocked exposure or rats not provided with access to the wheels. In Experiment 2, rats provided with access to the wheels immediately before or after a nonshocked exposure to the conditioned context froze less when tested in that context than rats provided with access to the wheels 6 h after the nonshocked exposure or rats not provided with access to the wheels. In Experiment 3, rats provided with access to wheels immediately after an extended nonshocked exposure to the conditioned context again froze less, whereas rats provided with access to the wheels after a brief nonshocked exposure froze more on the subsequent test than sedentary controls. These results show that a single bout of running can enhance acquisition, extinction, and reconsolidation of context conditioned fear.Pavlovian conditioned fear is thought to contribute to anxiety disorders such as post-traumatic stress, and extinction of this fear is a goal of exposure-based treatments of post-traumatic stress disorder (Bouton et al. 2001). Hence, there has been interest in identifying variables that regulate the acquisition and extinction of fear responses in animal models in order to better understand posttraumatic stress and develop more effective treatments for this disorder. One of the variables that influence the acquisition of conditioned fear in rodents is a history of exercise. Rodents provided with access to running wheels for several weeks and then shocked in a distinctive context exhibit more fear (typically freezing responses) than sedentary controls (Baruch et al.

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Norepinephrine and the dentate gyrus

Cited by 123 publications

References 151 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

Understanding Low Reliability of Memories for Neutral Information Encoded under Stress: Alterations in Memory-Related Activation in the Hippocampus and Midbrain

A bout of voluntary running enhances context conditioned fear, its extinction, and its reconsolidation

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