Novel Environments Enhance the Induction and Maintenance of Long-Term Potentiation in the Dentate Gyrus

Davis, Cyndy D.; Jones, Floretta L.; Derrick, Brian E.

doi:10.1523/jneurosci.4970-03.2004

Cited by 108 publications

(107 citation statements)

References 75 publications

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“…The VTA dopamine fibers are unique among biogenic amines innervating the hippocampus in that they participate in a rewarddetection system that promotes LTP and learning (4,35,36). During exploratory behaviors, when gamma-frequency activity occurs in the DG and DGCs fire at high rates (1,3,(37)(38)(39), the reward salience of an external stimulus is signaled by release of dopamine from VTA projections to the molecular layer of the DG (40).…”

Section: Discussionmentioning

confidence: 99%

Dopamine modulates synaptic plasticity in dendrites of rat and human dentate granule cells

Hamilton

Wheatley

Sinclair

et al. 2010

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

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The mechanisms underlying memory formation in the hippocampal network remain a major unanswered aspect of neuroscience. Although high-frequency activity appears essential for plasticity, salience for memory formation is also provided by activity in ventral tegmental area (VTA) dopamine projections. Here, we report that activation of dopamine D1 receptors in dentate granule cells (DGCs) can preferentially increase dendritic excitability to both highfrequency afferent activity and high-frequency trains of backpropagating action potentials. Using whole-cell patch clamp recordings, calcium imaging, and neuropeptide Y to inhibit postsynaptic calcium influx, we found that activation of dendritic voltagedependent calcium channels (VDCCs) is essential for dopamineinduced long-term potentiation (LTP), both in rat and human dentate gyrus (DG). Moreover, we demonstrate previously unreported spike-timing-dependent plasticity in the human hippocampus. These results suggest that when dopamine is released in the dentate gyrus with concurrent high-frequency activity there is an increased probability that synapses will be strengthened and reward-associated spatial memories will be formed.A s an animal explores a specific location, place cells in the dentate gyrus (DG) of the hippocampus fire bursts of action potentials (APs) (1) that can result in the formation of a new, long-term contextual memory (2). This is part of the "pattern separation" mechanism, whereby only a small population of dentate granule cells (DGCs) become very active and pass on the incoming cortical input to be later represented or "completed," in the downstream CA3 network (3). Memory formation related to a specific place can be enhanced by an associated salience, such as reward (4). Recent work suggests that disruption of mesocorticolimbic dopamine responses blocks conditioned place preference (CPP), a reward-driven form of spatial memory (5, 6). Furthermore, nicotine-induced CPP requires dopamine D1 receptor (D1R) activation in the DG (7). The medial perforant pathway (MPP) carries spatial information to the middle third of the molecular layer (8). In DGCs, D1Rs are concentrated throughout the dendritic tree (9). This suggests that bursting activity in DGCs, coincident with local dopamine release, may enhance formation of salient memories, but a mechanism remains unknown.One potential mechanism mediating plasticity is the coincidence of backpropagating dendritic APs with appropriately timed synaptic input (10); this mechanism requires postsynaptic Ca 2+ influx (11). Ca 2+ channels have been implicated in nonlinear, frequency-dependent responses in dendrites (12) and D1Rs can potentiate dendritic excitability in hippocampal area CA1 (13). Because the molecular layer of the DG is innervated by dopaminergic terminals from the ventral tegmental area (VTA) (14) we examined the possibility that interactions at the level of DGC dendrites between firing frequency, dendritic Ca 2+ responses, and D1Rs, may mediate plasticity in medial perforant path synaptic inputs....

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Section: Discussionmentioning

confidence: 99%

Dopamine modulates synaptic plasticity in dendrites of rat and human dentate granule cells

Hamilton

Wheatley

Sinclair

et al. 2010

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

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“…Permanent electrodes were implanted as described previously (Villarreal et al, 2002;Davis et al, 2004). Briefly, rats were anesthetized with pentobarbital sodium (Nembutal, 65 mg/kg, Henry Schein, Melville, NY) with supplemental injections (10 mg/kg) to maintain a surgical level of anesthesia.…”

Section: Methodsmentioning

confidence: 99%

“…Novel environments elicit exploration and theta rhythm, thought to reflect a sustained period over which the animal is acquiring new information (Davis et al, 2004). Novel environments were made from Plexiglas cages identical in size to the home cage (47 ϫ 25 ϫ 20 cm) and included fresh bedding and 4 -5 plastic or metal objects, such as boxes and small toys.…”

Section: Methodsmentioning

confidence: 99%

“…In studies assessing the effects of novel environments on intrinsic and extrinsic CA3 synaptic responses, we recorded field EPSPs evoked in both novel and familiar environments as described previously (Davis et al, 2004). Before data collection, animals were anesthetized briefly with isofluorane and connected to the recording apparatus, and placed in an isolation box while still in its home cage for a 30 min period to acclimate to the isolation box environment.…”

Section: E)mentioning

confidence: 99%

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Modulation of CA3 Afferent Inputs by Novelty and Theta Rhythm

Villarreal¹,

Gross²,

Derrick³

2007

J. Neurosci.

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Models of hippocampal function suggest that the modulation of CA3 afferent input during theta rhythm allows for a rapid alternation between encoding and retrieval states, with each phase enhancing either extrinsic or intrinsic CA3 afferents, favoring either encoding or retrieval, respectively. Here, we show that during the initial exploration of a novel environment by rats, intrinsic CA3-CA3 synaptic inputs are attenuated on CA3 theta peaks, favoring extrinsic CA3 inputs, whereas extrinsic perforant path-CA3 synaptic inputs are attenuated on CA3 theta troughs, favoring intrinsic CA3 inputs. This modulation is absent when animals are re-exposed to the same environment 2 or 48 h later and thus habituates with familiarity, suggesting a process involved in learning. Modulation of CA3 synaptic inputs during novelty was blocked by atropine at a dose that blocks type 2 theta rhythm. Re-exposure to the same novel environment 48 h later in the absence of atropine did not result in habituation, but instead modulated CA3 synaptic responses as though the environment were novel and explored for the first time. The NMDA receptor antagonist (Ϯ)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP), administered in a dose that blocks long-term potentiation induction, did not alter CA3 synaptic modulation during initial exploration. However, like atropine, CPP blocked the habituation of synaptic modulation normally observed with re-exposure, as though the environment were novel and explored for the first time. Thus, as predicted theoretically, recurrent and cortical CA3 afferents are differentially modulated during phases of theta rhythm. This modulation is atropine sensitive and habituates in an NMDA receptor-dependent manner, suggesting an NMDA receptor-dependent process that, in conjunction with theta rhythm, contributes to encoding of novel information in the hippocampus.

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“…Novelty modulates various forms of hippocampus-dependent plasticity. Exploration of a novel context can either enhance or impair long-term potentiation in the hippocampus (Xu et al 1998;Abraham et al 2002;Li et al 2003;Straube et al 2003;Davis et al 2004) and can strengthen learning in a variety of hippocampus-dependent tasks (Moncada and Viola 2007;Ballarini et al 2009;Almaguer-Melian et al 2012). A recent study demonstrated that exposure to a novel context can enhance extinction of CFC (de Carvalho Myskiw et al 2013).…”

Section: Discussionmentioning

confidence: 99%

Potent attenuation of context fear by extinction training contiguous with acquisition

Bernier

Lacagnina

Drew³

2014

Learn. Mem.

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Studies on the behavioral mechanisms underlying contextual fear conditioning (CFC) have demonstrated the importance of preshock context exposure in the formation of aversive context memories. However, there has been comparatively little investigation of the effects of context exposure immediately after the shock. Some models predict that nonreinforced context exposure at the end of the acquisition session will strongly influence the strength of conditioning and/or recruit distinct neural mechanisms relative to extinction after acquisition. Here we investigate the effects of manipulating postshock context exposure on CFC in mice. Prolonging the period of context exposure immediately following the shock caused a significant and durable reduction in conditioned fear. This immediate postshock context exposure was more effective at attenuating conditioned fear than was an equivalent amount of context exposure a day or more after acquisition. The results suggest that nonreinforced exposure to the context influences conditioned fear through distinct mechanisms depending on whether it occurs during acquisition or after it. The superiority of immediate postshock context exposure was specific to single-shock CFC; in two-shock CFC, immediate and delayed postshock context exposure had similar effects. Consistent with previous reports, we hypothesize that the effectiveness of extinction is modulated by emotional state, and procedures engendering higher postshock freezing (such as two-shock CFC) are associated with weaker immediate extinction.Contextual fear conditioning (CFC) is a form of associative learning that occurs when an aversive experience, usually a footshock in laboratory experiments, occurs within a distinctive place or context. Learned contextual fear typically recruits plasticity in the hippocampus, which is thought to generate a conjunctive mnemonic representation of stimuli present during the learning episode (Rudy et al. 2004;Fanselow 2010). The robustness of this form of learning has made it one of the preferred methods for studying mechanisms of hippocampus-dependent memory and learned fear.While the neural mechanisms of CFC have been researched extensively, there has been comparatively little investigation of the behavioral mechanisms through which the emotional valence of a context is established. One longstanding idea is that the strength of context conditioning is determined by the overall rate of unconditioned stimulus (US) presentation per unit time in the context (Rescorla and Wagner 1972;Gibbon and Balsam 1981). This approach accounts for the observation that increasing the intertrial interval in conditioning experiments tends to decrease the amount of conditioned responding elicited by the context (Fanselow et al. 1993;Barela 1999). However, this model fails to account for a key property of CFC: very brief preshock context exposure leads to an absence of context fear, rather than robust fear as the rate-based model would predict (Fanselow 1986). This phenomenon, known as the immediate shock defici...

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Novel Environments Enhance the Induction and Maintenance of Long-Term Potentiation in the Dentate Gyrus

Cited by 108 publications

References 75 publications

Dopamine modulates synaptic plasticity in dendrites of rat and human dentate granule cells

Dopamine modulates synaptic plasticity in dendrites of rat and human dentate granule cells

Modulation of CA3 Afferent Inputs by Novelty and Theta Rhythm

Potent attenuation of context fear by extinction training contiguous with acquisition

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