The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Michael S. Fanselow - One of the best experts on this subject based on the ideXlab platform.
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contextual fear memories formed in the absence of the Dorsal Hippocampus decay across time
The Journal of Neuroscience, 2012Co-Authors: Moriel Zelikowsky, Stephanie Bissiere, Michael S. FanselowAbstract:Mammals suffering damage to the Hippocampus display a dramatic loss of explicit, recently formed memories (retrograde amnesia). In contrast, deficits in the ability to form new memories following hippocampal damage (anterograde amnesia) can be overcome with sufficient training. By combining contextual fear conditioning with lesions of the Dorsal Hippocampus in rats, we discovered that while animals can form long-term contextual fear memories in the absence of the Hippocampus, these memories decay with time, lacking the permanence that is a hallmark characteristic of normal fear memories. These findings indicate that while it is initially possible to acquire explicit memories when the Hippocampus is compromised, these memories cannot transfer from a recent to remote state. This suggests that memories formed outside the Hippocampus may nevertheless require the Hippocampus to undergo systems consolidation, which has important clinical implications for the treatment of memory disorders.
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Dorsal Hippocampus involvement in delay fear conditioning depends upon the strength of the tone footshock association
Hippocampus, 2008Co-Authors: Jennifer J. Quinn, Heather M Wied, Quang D, Matthew R Tinsley, Michael S. FanselowAbstract:The Hippocampus is important for the formation of spatial, contextual, and episodic memories. For instance, lesions of the Dorsal Hippocampus (DH) produce demonstrable deficits in contextual fear conditioning. By contrast, it is generally agreed that the DH is not important for conditioning to a discrete cue (such as a tone or light) that is paired with footshock in a temporally contiguous fashion (delay conditioning). There are, however, some reports of Hippocampus involvement in delay conditioning. The present series of experiments was designed to assess the conditions under which the Hippocampus-dependent component of delay fear conditioning performance may be revealed. Here, we manipulated the number of conditioning trials and the intensity of the footshock in order to vary the strength of conditioning. The results indicate that the DH contributes to freezing performance to a delay conditioned tone when the conditioning parameters are relatively weak (few trials or low footshock intensity), but not when strong parameters are used. The results are discussed in terms of two parallel memory systems: a direct tone-footshock association that is independent of the Hippocampus and a Hippocampus-dependent memory for the conditioning session. © 2008 Wiley-Liss, Inc.
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Dorsal Hippocampus involvement in delay fear conditioning depends upon the strength of the tone footshock association
Hippocampus, 2008Co-Authors: Jennifer J. Quinn, Heather M Wied, Quang D, Matthew R Tinsley, Michael S. FanselowAbstract:The Hippocampus is important for the formation of spatial, contextual, and episodic memories. For instance, lesions of the Dorsal Hippocampus (DH) produce demonstrable deficits in contextual fear conditioning. By contrast, it is generally agreed that the DH is not important for conditioning to a discrete cue (such as a tone or light) that is paired with footshock in a temporally contiguous fashion (delay conditioning). There are, however, some reports of Hippocampus involvement in delay conditioning. The present series of experiments was designed to assess the conditions under which the Hippocampus-dependent component of delay fear conditioning performance may be revealed. Here, we manipulated the number of conditioning trials and the intensity of the footshock in order to vary the strength of conditioning. The results indicate that the DH contributes to freezing performance to a delay conditioned tone when the conditioning parameters are relatively weak (few trials or low footshock intensity), but not when strong parameters are used. The results are discussed in terms of two parallel memory systems: a direct tone-footshock association that is independent of the Hippocampus and a Hippocampus-dependent memory for the conditioning session.
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inverse temporal contributions of the Dorsal Hippocampus and medial prefrontal cortex to the expression of long term fear memories
Learning & Memory, 2008Co-Authors: Jennifer J. Quinn, Quang D, Matthew R Tinsley, Christof Koch, Michael S. FanselowAbstract:Retrograde amnesia following disruptions of hippocampal function is often temporally graded, with recent memories being more impaired. Evidence supports the existence of one or more neocortical long-term memory storage/retrieval site(s). Neurotoxic lesions of the medial prefrontal cortex (mPFC) or the Dorsal Hippocampus (DH) were made 1 day or 200 days following trace fear conditioning. Recently encoded trace fear memories were most disrupted by DH lesions, while remotely encoded trace and contextual memories were most disrupted by mPFC lesions. These data strongly support the consolidation theory of Hippocampus function and implicate the mPFC as a site of long-term memory storage/retrieval.
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Dorsal Hippocampus involvement in trace fear conditioning with long but not short trace intervals in mice
Behavioral Neuroscience, 2005Co-Authors: Najwa Chowdhury, Jennifer J. Quinn, Michael S. FanselowAbstract:Placing a "trace" interval between a warning signal and an aversive shock makes consolidation of the memory for trace conditioning Hippocampus dependent. To determine the trace at which memory consolidation requires the Hippocampus, mice were trained with 0-s, 1-s, 3-s, or 20-s trace intervals and tested for freezing to context and tone. Posttraining Dorsal Hippocampus (DH) lesions decreased context conditioning regardless of trace interval. However, DH lesions attenuated only the 20-s trace tone freezing. Like eyeblink conditioning, the DH is necessary for trace fear conditioning only at long trace intervals, but the time scale for the effective interval in fear conditioning is about 40 times longer. Manipulations that alter trace fear conditioning with short trace intervals probably do not reflect altered DH function. Given this difference in time scale along with the use of posttraining DH lesions, Hippocampus dependency of trace conditioning is not related to a bridging function or response timing.
Jennifer J. Quinn - One of the best experts on this subject based on the ideXlab platform.
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Dorsal Hippocampus involvement in delay fear conditioning depends upon the strength of the tone footshock association
Hippocampus, 2008Co-Authors: Jennifer J. Quinn, Heather M Wied, Quang D, Matthew R Tinsley, Michael S. FanselowAbstract:The Hippocampus is important for the formation of spatial, contextual, and episodic memories. For instance, lesions of the Dorsal Hippocampus (DH) produce demonstrable deficits in contextual fear conditioning. By contrast, it is generally agreed that the DH is not important for conditioning to a discrete cue (such as a tone or light) that is paired with footshock in a temporally contiguous fashion (delay conditioning). There are, however, some reports of Hippocampus involvement in delay conditioning. The present series of experiments was designed to assess the conditions under which the Hippocampus-dependent component of delay fear conditioning performance may be revealed. Here, we manipulated the number of conditioning trials and the intensity of the footshock in order to vary the strength of conditioning. The results indicate that the DH contributes to freezing performance to a delay conditioned tone when the conditioning parameters are relatively weak (few trials or low footshock intensity), but not when strong parameters are used. The results are discussed in terms of two parallel memory systems: a direct tone-footshock association that is independent of the Hippocampus and a Hippocampus-dependent memory for the conditioning session. © 2008 Wiley-Liss, Inc.
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Dorsal Hippocampus involvement in delay fear conditioning depends upon the strength of the tone footshock association
Hippocampus, 2008Co-Authors: Jennifer J. Quinn, Heather M Wied, Quang D, Matthew R Tinsley, Michael S. FanselowAbstract:The Hippocampus is important for the formation of spatial, contextual, and episodic memories. For instance, lesions of the Dorsal Hippocampus (DH) produce demonstrable deficits in contextual fear conditioning. By contrast, it is generally agreed that the DH is not important for conditioning to a discrete cue (such as a tone or light) that is paired with footshock in a temporally contiguous fashion (delay conditioning). There are, however, some reports of Hippocampus involvement in delay conditioning. The present series of experiments was designed to assess the conditions under which the Hippocampus-dependent component of delay fear conditioning performance may be revealed. Here, we manipulated the number of conditioning trials and the intensity of the footshock in order to vary the strength of conditioning. The results indicate that the DH contributes to freezing performance to a delay conditioned tone when the conditioning parameters are relatively weak (few trials or low footshock intensity), but not when strong parameters are used. The results are discussed in terms of two parallel memory systems: a direct tone-footshock association that is independent of the Hippocampus and a Hippocampus-dependent memory for the conditioning session.
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inverse temporal contributions of the Dorsal Hippocampus and medial prefrontal cortex to the expression of long term fear memories
Learning & Memory, 2008Co-Authors: Jennifer J. Quinn, Quang D, Matthew R Tinsley, Christof Koch, Michael S. FanselowAbstract:Retrograde amnesia following disruptions of hippocampal function is often temporally graded, with recent memories being more impaired. Evidence supports the existence of one or more neocortical long-term memory storage/retrieval site(s). Neurotoxic lesions of the medial prefrontal cortex (mPFC) or the Dorsal Hippocampus (DH) were made 1 day or 200 days following trace fear conditioning. Recently encoded trace fear memories were most disrupted by DH lesions, while remotely encoded trace and contextual memories were most disrupted by mPFC lesions. These data strongly support the consolidation theory of Hippocampus function and implicate the mPFC as a site of long-term memory storage/retrieval.
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Dorsal Hippocampus involvement in trace fear conditioning with long but not short trace intervals in mice
Behavioral Neuroscience, 2005Co-Authors: Najwa Chowdhury, Jennifer J. Quinn, Michael S. FanselowAbstract:Placing a "trace" interval between a warning signal and an aversive shock makes consolidation of the memory for trace conditioning Hippocampus dependent. To determine the trace at which memory consolidation requires the Hippocampus, mice were trained with 0-s, 1-s, 3-s, or 20-s trace intervals and tested for freezing to context and tone. Posttraining Dorsal Hippocampus (DH) lesions decreased context conditioning regardless of trace interval. However, DH lesions attenuated only the 20-s trace tone freezing. Like eyeblink conditioning, the DH is necessary for trace fear conditioning only at long trace intervals, but the time scale for the effective interval in fear conditioning is about 40 times longer. Manipulations that alter trace fear conditioning with short trace intervals probably do not reflect altered DH function. Given this difference in time scale along with the use of posttraining DH lesions, Hippocampus dependency of trace conditioning is not related to a bridging function or response timing.
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Dorsal Hippocampus NMDA receptors differentially mediate trace and contextual fear conditioning
Hippocampus, 2005Co-Authors: Jennifer J. Quinn, Quang D, Fred Loya, Michael S. FanselowAbstract:The Dorsal Hippocampus (DH) is critically involved in the acquisition and expression of trace and contextual fear conditioning. NMDA/glutamate receptor-mediated transmission is thought to be one mechanism mediating the plastic changes that support long-term memories in the DH. However, their precise involvement in acquisition and expression processes has not been defined. To examine this issue, the NMDA receptor antagonist, D,L-2-amino-5-phosphonovaleric acid (APV; 10 μg/μl; 0.5 μl), was infused into the DH prior to conditioning and/or testing, using a trace fear conditioning procedure. All rats were tested for freezing to both tone and context in separate, counterbalanced sessions. The three sessions (1 training and 2 test) were separated by approximately 24 h. Using this design, it was possible to assess the role for DH NMDA receptors in the acquisition versus expression of trace and contextual fear conditioning. APV disrupted acquisition, but not expression, of contextual fear conditioning. By contrast, APV attenuated both acquisition and expression of trace fear memories. Thus, DH NMDA receptors appear to contribute to retrieval of some, but not all, fear memories. ©2005 Wiley-Liss, Inc.
Karyn M Frick - One of the best experts on this subject based on the ideXlab platform.
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estradiol mediated spine changes in the Dorsal Hippocampus and medial prefrontal cortex of ovariectomized female mice depend on erk and mtor activation in the Dorsal Hippocampus
The Journal of Neuroscience, 2016Co-Authors: Jennifer J Tuscher, Victoria N Luine, Maya Frankfurt, Karyn M FrickAbstract:Dendritic spine plasticity underlies the formation and maintenance of memories. Both natural fluctuations and systemic administration of 17β-estradiol (E2) alter spine density in the Dorsal Hippocampus (DH) of rodents. DH E2 infusion enhances hippocampal-dependent memory by rapidly activating extracellular signal-regulated kinase (ERK)-dependent signaling of mammalian target of rapamycin (mTOR), a key protein synthesis pathway involved in spine remodeling. Here, we investigated whether infusion of E2 directly into the DH drives spine changes in the DH and other brain regions, and identified cell-signaling pathways that mediate these effects. E2 significantly increased basal and apical spine density on CA1 pyramidal neurons 30 min and 2 h after infusion. DH E2 infusion also significantly increased basal spine density on pyramidal neurons in the medial prefrontal cortex (mPFC) 2 h later, suggesting that E2-mediated activity in the DH drives mPFC spinogenesis. The increase in CA1 and mPFC spine density observed 2 h after intracerebroventricular infusion of E2 was blocked by DH infusion of an ERK or mTOR inhibitor. DH E2 infusion did not affect spine density in the dentate gyrus or ventromedial hypothalamus, suggesting specific effects of E2 on the DH and mPFC. Collectively, these data demonstrate that DH E2 treatment elicits ERK- and mTOR-dependent spinogenesis on CA1 and mPFC pyramidal neurons, effects that may support the memory-enhancing effects of E2. SIGNIFICANCE STATEMENT Although systemically injected 17β-estradiol (E2) increases CA1 dendritic spine density, the molecular mechanisms regulating E2-induced spinogenesis in vivo are largely unknown. We found that E2 infused directly into the Dorsal Hippocampus (DH) increased CA1 spine density 30 min and 2 h later. Surprisingly, DH E2 infusion also increased spine density in the medial prefrontal cortex (mPFC), suggesting that estrogenic regulation of the DH influences mPFC spinogenesis. Moreover, inhibition of ERK and mTOR activation in the DH prevented E2 from increasing DH and mPFC spines, demonstrating that DH ERK and mTOR activation is necessary for E2-induced spinogenesis in the DH and mPFC. These findings provide novel insights into the molecular mechanisms through which E2 mediates dendritic spine density in CA1 and mPFC.
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estradiol induced object recognition memory consolidation is dependent on activation of mtor signaling in the Dorsal Hippocampus
Learning & Memory, 2013Co-Authors: Ashley M Fortress, Zaorui Zhao, Karyn M FrickAbstract:The mammalian target of rapamycin (mTOR) signaling pathway is an important regulator of protein synthesis and is essential for various forms of hippocampal memory. Here, we asked whether the enhancement of object recognition memory consolidation produced by Dorsal hippocampal infusion of 17b-estradiol (E2) is dependent on mTOR signaling in the Dorsal Hippocampus, and whether E2-induced mTOR signaling is dependent on Dorsal hippocampal phosphatidylinositol 3-kinase (PI3K) and extracellular signal-regulated kinase (ERK) activation. We first demonstrated that the enhancement of object recognition induced by E2 was blocked by Dorsal hippocampal inhibition of ERK, PI3K, or mTOR activation. We then showed that an increase in Dorsal hippocampal ERK phosphorylation 5 min after intracerebroventricular (ICV) E2 infusion was also blocked by Dorsal hippocampal infusion of the three cell signaling inhibitors. Next, we found that ICV infusion of E2 increased phosphorylation of the downstream mTOR targets S6K (Thr-421) and 4E-BP1 in the Dorsal Hippocampus 5 min after infusion, and that this phosphorylation was blocked by Dorsal hippocampal infusion of inhibitors of ERK, PI3K, and mTOR. Collectively, these data demonstrate for the first time that activation of the Dorsal hippocampal mTOR signaling pathway is necessary for E2 to enhance object recognition memory consolidation and that E2-induced mTOR activation is dependent on upstream activation of ERK and PI3K signaling.
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the progesterone induced enhancement of object recognition memory consolidation involves activation of the extracellular signal regulated kinase erk and mammalian target of rapamycin mtor pathways in the Dorsal Hippocampus
Hormones and Behavior, 2012Co-Authors: Patrick T Orr, Karyn M Frick, Amanda J Rubin, Lu Fan, Brianne A KentAbstract:Although much recent work has elucidated the biochemical mechanisms underlying the modulation of memory by 17β-estradiol, little is known about the signaling events through which progesterone (P) regulates memory. We recently demonstrated that immediate post-training infusion of P into the Dorsal Hippocampus enhances object recognition memory consolidation in young ovariectomized female mice (Orr et al., 2009). The goal of the present study was to identify the biochemical alterations that might underlie this mnemonic enhancement. We hypothesized that the P-induced enhancement of object recognition would be dependent on activation of the ERK and mTOR pathways. In young ovariectomized mice, we found that bilateral Dorsal hippocampal infusion of P significantly increased levels of phospho-p42 ERK and the mTOR substrate S6K in the Dorsal Hippocampus 5 min after infusion. Phospho-p42 ERK levels were downregulated 15 min after infusion and returned to baseline 30 min after infusion, suggesting a biphasic effect of P on ERK activation. Dorsal hippocampal ERK and mTOR activation were necessary for P to facilitate memory consolidation, as suggested by the fact that inhibitors of both pathways infused into the Dorsal Hippocampus immediately after training blocked the P-induced enhancement of object recognition. Collectively, these data provide the first demonstration that the ability of P to enhance memory consolidation depends on the rapid activation of cell signaling and protein synthesis pathways in the Dorsal Hippocampus.
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estradiol induced enhancement of object memory consolidation involves nmda receptors and protein kinase a in the Dorsal Hippocampus of female c57bl 6 mice
Behavioral Neuroscience, 2008Co-Authors: Michael C Lewis, Patrick T Orr, Kristin M Kerr, Karyn M FrickAbstract:This study examined the role of Dorsal hippocampal NMDA receptors and PKA activation in 17 beta-estradiol (E2)-induced enhancement of object memory consolidation. Mice explored two identical objects during training, after which they immediately received intraperitoneal injections of 0.2 mg/kg E2, and bilateral Dorsal hippocampal infusions of Vehicle, the NMDA receptor antagonist APV (2.5 microg/side), or the cAMP inhibitor Rp-cAMPS (18.0 microg/side). Retention was tested 48 hours later. The enhanced object memory and increased ERK phosphorylation observed with E2 alone was reduced by APV and Rp-cAMPS, suggesting that estrogenic enhancement of object memory involves NMDA receptors and PKA activation within the Dorsal Hippocampus.
Quang D - One of the best experts on this subject based on the ideXlab platform.
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Dorsal Hippocampus involvement in delay fear conditioning depends upon the strength of the tone footshock association
Hippocampus, 2008Co-Authors: Jennifer J. Quinn, Heather M Wied, Quang D, Matthew R Tinsley, Michael S. FanselowAbstract:The Hippocampus is important for the formation of spatial, contextual, and episodic memories. For instance, lesions of the Dorsal Hippocampus (DH) produce demonstrable deficits in contextual fear conditioning. By contrast, it is generally agreed that the DH is not important for conditioning to a discrete cue (such as a tone or light) that is paired with footshock in a temporally contiguous fashion (delay conditioning). There are, however, some reports of Hippocampus involvement in delay conditioning. The present series of experiments was designed to assess the conditions under which the Hippocampus-dependent component of delay fear conditioning performance may be revealed. Here, we manipulated the number of conditioning trials and the intensity of the footshock in order to vary the strength of conditioning. The results indicate that the DH contributes to freezing performance to a delay conditioned tone when the conditioning parameters are relatively weak (few trials or low footshock intensity), but not when strong parameters are used. The results are discussed in terms of two parallel memory systems: a direct tone-footshock association that is independent of the Hippocampus and a Hippocampus-dependent memory for the conditioning session. © 2008 Wiley-Liss, Inc.
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Dorsal Hippocampus involvement in delay fear conditioning depends upon the strength of the tone footshock association
Hippocampus, 2008Co-Authors: Jennifer J. Quinn, Heather M Wied, Quang D, Matthew R Tinsley, Michael S. FanselowAbstract:The Hippocampus is important for the formation of spatial, contextual, and episodic memories. For instance, lesions of the Dorsal Hippocampus (DH) produce demonstrable deficits in contextual fear conditioning. By contrast, it is generally agreed that the DH is not important for conditioning to a discrete cue (such as a tone or light) that is paired with footshock in a temporally contiguous fashion (delay conditioning). There are, however, some reports of Hippocampus involvement in delay conditioning. The present series of experiments was designed to assess the conditions under which the Hippocampus-dependent component of delay fear conditioning performance may be revealed. Here, we manipulated the number of conditioning trials and the intensity of the footshock in order to vary the strength of conditioning. The results indicate that the DH contributes to freezing performance to a delay conditioned tone when the conditioning parameters are relatively weak (few trials or low footshock intensity), but not when strong parameters are used. The results are discussed in terms of two parallel memory systems: a direct tone-footshock association that is independent of the Hippocampus and a Hippocampus-dependent memory for the conditioning session.
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inverse temporal contributions of the Dorsal Hippocampus and medial prefrontal cortex to the expression of long term fear memories
Learning & Memory, 2008Co-Authors: Jennifer J. Quinn, Quang D, Matthew R Tinsley, Christof Koch, Michael S. FanselowAbstract:Retrograde amnesia following disruptions of hippocampal function is often temporally graded, with recent memories being more impaired. Evidence supports the existence of one or more neocortical long-term memory storage/retrieval site(s). Neurotoxic lesions of the medial prefrontal cortex (mPFC) or the Dorsal Hippocampus (DH) were made 1 day or 200 days following trace fear conditioning. Recently encoded trace fear memories were most disrupted by DH lesions, while remotely encoded trace and contextual memories were most disrupted by mPFC lesions. These data strongly support the consolidation theory of Hippocampus function and implicate the mPFC as a site of long-term memory storage/retrieval.
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Dorsal Hippocampus NMDA receptors differentially mediate trace and contextual fear conditioning
Hippocampus, 2005Co-Authors: Jennifer J. Quinn, Quang D, Fred Loya, Michael S. FanselowAbstract:The Dorsal Hippocampus (DH) is critically involved in the acquisition and expression of trace and contextual fear conditioning. NMDA/glutamate receptor-mediated transmission is thought to be one mechanism mediating the plastic changes that support long-term memories in the DH. However, their precise involvement in acquisition and expression processes has not been defined. To examine this issue, the NMDA receptor antagonist, D,L-2-amino-5-phosphonovaleric acid (APV; 10 μg/μl; 0.5 μl), was infused into the DH prior to conditioning and/or testing, using a trace fear conditioning procedure. All rats were tested for freezing to both tone and context in separate, counterbalanced sessions. The three sessions (1 training and 2 test) were separated by approximately 24 h. Using this design, it was possible to assess the role for DH NMDA receptors in the acquisition versus expression of trace and contextual fear conditioning. APV disrupted acquisition, but not expression, of contextual fear conditioning. By contrast, APV attenuated both acquisition and expression of trace fear memories. Thus, DH NMDA receptors appear to contribute to retrieval of some, but not all, fear memories. ©2005 Wiley-Liss, Inc.
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Dorsal Hippocampus nmda receptors differentially mediate trace and contextual fear conditioning
Hippocampus, 2005Co-Authors: Jennifer J. Quinn, Quang D, Fred Loya, Michael S. FanselowAbstract:The Dorsal Hippocampus (DH) is critically involved in the acquisition and expression of trace and contextual fear conditioning. NMDA/glutamate receptor-mediated transmission is thought to be one mechanism mediating the plastic changes that support long-term memories in the DH. However, their precise involvement in acquisition and expression processes has not been defined. To examine this issue, the NMDA receptor antagonist, D,L-2-amino-5-phosphonovaleric acid (APV; 10 microg/microl; 0.5 microl), was infused into the DH prior to conditioning and/or testing, using a trace fear conditioning procedure. All rats were tested for freezing to both tone and context in separate, counterbalanced sessions. The three sessions (1 training and 2 test) were separated by approximately 24 h. Using this design, it was possible to assess the role for DH NMDA receptors in the acquisition versus expression of trace and contextual fear conditioning. APV disrupted acquisition, but not expression, of contextual fear conditioning. By contrast, APV attenuated both acquisition and expression of trace fear memories. Thus, DH NMDA receptors appear to contribute to retrieval of some, but not all, fear memories.
Oliver Stiedl - One of the best experts on this subject based on the ideXlab platform.
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injection of galanin into the Dorsal Hippocampus impairs emotional memory independent of 5 ht1a receptor activation
Behavioural Brain Research, 2021Co-Authors: Eugenia Kuteeva, Oliver Stiedl, Tomas Hokfelt, Sven Ove OgrenAbstract:Abstract There is evidence that interaction between the neuropeptide galanin and the 5-HT1A receptor represents an integrative mechanism in the regulation of serotonergic neurotransmission. Thus, in rats intracerebroventricular (i.c.v.) galanin did not impair retention in the passive avoidance (PA) test 24 h after training, but attenuated the retention deficit caused by subcutaneous (s.c.) administration of the 5-HT1A receptor agonist 8-OH-DPAT. This impairment has been linked to postsynaptic 5-HT1A receptor activation. To confirm these results in mice, galanin was infused i.c.v. (1 nmol/mouse) in C57BL/6/Bkl mice 30 min prior to training followed by s.c. injection (0.3 mg/kg) of 8-OH-DPAT or saline 15 min before PA training. In line with previous results, i.c.v. galanin significantly attenuated the PA impairment caused by 5-HT1A receptor activation in mice. To study if the galanin 5-HT1A receptor interaction involved the Dorsal Hippocampus, galanin (1 nmol/mouse) was directly infused into this brain region alone or in combination with s.c. 8-OH-DPAT. However, unlike i.c.v. galanin, galanin infusion into the Dorsal Hippocampus alone impaired PA retention and failed to attenuate the 8-OH-DPAT-mediated PA impairment. These results indicate that the ability of i.c.v. galanin to modify 5-HT1A receptor activation is not directly mediated via receptor interactions in the Dorsal Hippocampus. Instead, the galanin-mediated PA impairment suggests an important inhibitory role of galanin receptors in the Dorsal Hippocampus for acquisition (encoding) and/or consolidation of emotional memory. In addition, the interaction between galanin and 5-HT1A receptors probably involves a wide serotonergic network that is important for the integration of emotional and cognitive behaviors.
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time dependent involvement of the Dorsal Hippocampus in trace fear conditioning in mice
Hippocampus, 2005Co-Authors: Ilga Misane, Philip Tovote, Michael Meyer, Joachim Spiess, Sven Ove Ogren, Oliver StiedlAbstract:Hippocampal and amygdaloid neuroplasticity are important substrates for Pavlovian fear conditioning. The Hippocampus has been implicated in trace fear conditioning. However, a systematic investigation of the significance of the trace interval has not yet been performed. Therefore, this study analyzed the time-dependent involvement of N-methyl-D-aspartate (NMDA) receptors in the Dorsal Hippocampus in one-trial auditory trace fear conditioning in C57BL/6J mice. The NMDA receptor antagonist APV was injected bilaterally into the Dorsal Hippocampus 15 min before training. Mice were exposed to tone (conditioned stimulus [CS]) and footshock (unconditioned stimulus [US]) in the conditioning context without delay (0 s) or with CS-US (trace) intervals of 1-45 s. Conditioned auditory fear was determined 24 h after training by the assessment of freezing and computerized evaluation of inactivity in a new context; 2 h later, context-dependent memory was tested in the conditioning context. NMDA receptor blockade by APV markedly impaired conditioned auditory fear at trace intervals of 15 s and 30 s, but not at shorter trace intervals. A 45-s trace interval prevented the formation of conditioned tone-dependent fear. Context-dependent memory was always impaired by APV treatment independent of the trace interval. The results indicate that the Dorsal Hippocampus and its NMDA receptors play an important role in auditory trace fear conditioning at trace intervals of 15-30-s length. In contrast, NMDA receptors in the Dorsal Hippocampus are unequivocally involved in contextual fear conditioning independent of the trace interval. The results point at a time-dependent role of the Dorsal Hippocampus in encoding of noncontingent explicit stimuli. Preprocessing of long CS-US contingencies in the Hippocampus appears to be important for the final information processing and execution of fear memories through amygdala circuits. © 2005 Wiley-Liss, Inc.