Time‐dependent involvement of the dorsal hippocampus in trace fear conditioning in mice

Misane, Ilga; Tovote, Philip; Meyer, Michaël; Spiess, Joachim; Ögren, Sven Ove; Stiedl, Oliver

doi:10.1002/hipo.20067

Cited by 162 publications

(191 citation statements)

References 42 publications

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“…By contrast, we (Czerniaswki et al, 2011) and others (e.g. Misane et al, 2005) have found that NMDA receptor antagonism within DH prior to training blocks the acquisition of trace fear conditioning. These data collectively suggest that DH may normally participate in both the acquisition and consolidation of trace fear conditioning, but is not necessary for either acquisition or recall.…”

Section: Histologycontrasting

confidence: 72%

Time course of dorsal and ventral hippocampal involvement in the expression of trace fear conditioning

Cox

Czerniawski

Ree

et al. 2013

Neurobiology of Learning and Memory

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It is becoming increasingly clear that the time-dependent involvement of the hippocampus in the recall of acquired behaviors is more complicated than once thought.Several early studies demonstrated that hippocampal damage attenuates the expression of recent, but not remotely trained tasks. By contrast, an emerging body of evidence has shown that damage to, or inactivation of, the hippocampus impairs recall across a wide range of training-testing intervals. Collectively, these data suggest that the time course of hippocampal involvement in the storage or recall of previouslyacquired memories differs according to hippocampal subregion and the particular learning task under consideration. The present study examined the contributions of dorsal (DH) and ventral (VH) hippocampus to the expression of previously-acquired trace fear conditioning, a form of Pavlovian conditioning in which the presentation of an initially neutral cue or cues and a subsequent aversive stimulus is separated by a nostimulus (trace) interval. Specifically, either the GABA-A agonist muscimol or saline was ii infused into the DH or VH prior to testing 1, 7, 28, or 42 days after trace fear conditioning. The results revealed a marked dissociation: pre-testing inactivation of DH failed to impair performance at any time-point, while pre-testing inactivation of VH impaired performance at all time-points. Importantly, pre-testing inactivation of VH had no effect on the performance during testing of previously-acquired delay conditioning.Collectively, these data suggest that VH, but not DH, remains a neuroanatomical locus critical to the recall or expression of trace fear conditioning over an extended period of time.

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Section: Histologycontrasting

confidence: 72%

Time course of dorsal and ventral hippocampal involvement in the expression of trace fear conditioning

Cox

Czerniawski

Ree

et al. 2013

Neurobiology of Learning and Memory

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“…The disruption of NMDAR signaling in the hippocampus disrupts trace, but not delay, fear conditioning (Misane et al, 2005). Our previous studies indicate that MgT treatment enhances NMDAR signaling and synaptic plasticity in the hippocampus (Slutsky et al, 2010).…”

Section: Effects Of Mgt Treatment On Conditioned Fear Memoriesmentioning

confidence: 89%

Effects of Elevation of Brain Magnesium on Fear Conditioning, Fear Extinction, and Synaptic Plasticity in the Infralimbic Prefrontal Cortex and Lateral Amygdala

Abumaria¹,

Yin²,

Zhang³

et al. 2011

J. Neurosci.

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Anxiety disorders, such as phobias and posttraumatic stress disorder, are among the most common mental disorders. Cognitive therapy helps in treating these disorders; however, many cases relapse or resist the therapy, which justifies the search for cognitive enhancers that might augment the efficacy of cognitive therapy. Studies suggest that enhancement of plasticity in certain brain regions such as the prefrontal cortex (PFC) and/or hippocampus might enhance the efficacy of cognitive therapy. We found that elevation of brain magnesium, by a novel magnesium compound [magnesium-L-threonate (MgT)], enhances synaptic plasticity in the hippocampus and learning and memory in rats. Here, we show that MgT treatment enhances retention of the extinction of fear memory, without enhancing, impairing, or erasing the original fear memory. We then explored the molecular basis of the effects of MgT treatment on fear memory and extinction. In intact animals, elevation of brain magnesium increased NMDA receptors (NMDARs) signaling, BDNF expression, density of presynaptic puncta, and synaptic plasticity in the PFC but, interestingly, not in the basolateral amygdala. In vitro, elevation of extracellular magnesium concentration increased synaptic NMDAR current and plasticity in the infralimbic PFC, but not in the lateral amygdala, suggesting a difference in their sensitivity to elevation of brain magnesium. The current study suggests that elevation of brain magnesium might be a novel approach for enhancing synaptic plasticity in a regional-specific manner leading to enhancing the efficacy of extinction without enhancing or impairing fear memory formation.

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“…Unlike delay conditioning where the tone (conditioned stimulus, CS) and shock (unconditioned stimulus, US) coterminate (49), trace fear conditioning, which places a time interval between the CS and US, makes both the contextual and auditory memories hippocampal-dependent (50)(51)(52)(53). Moreover, NMDARs in the hippocampus are also required for auditory (CS) memory following trace fear conditioning (51,52). There was no difference in the amount of freezing at baseline or at the end of fear conditioning across groups on day 1 (Fig.…”

Section: +mentioning

confidence: 99%

Multiple risk pathways for schizophrenia converge in serine racemase knockout mice, a mouse model of NMDA receptor hypofunction

Balu

Puhl

et al. 2013

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

199

201

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Schizophrenia is characterized by reduced hippocampal volume, decreased dendritic spine density, altered neuroplasticity signaling pathways, and cognitive deficits associated with impaired hippocampal function. We sought to determine whether this diverse pathology could be linked to NMDA receptor (NMDAR) hypofunction, and thus used the serine racemase-null mutant mouse (SR −/− ), which has less than 10% of normal brain D-serine, an NMDAR coagonist. We found that D-serine was necessary for the maintenance of long-term potentiation in the adult hippocampal dentate gyrus and for full NMDAR activity on granule cells. SR −/− mice had reduced dendritic spines and hippocampal volume. These morphological changes were paralleled by diminished BDNF/Akt/mammalian target of rapamycin (mTOR) signaling and impaired performance on a traceconditioning memory task. Chronic D-serine treatment normalized the electrophysiological, neurochemical, and cognitive deficits in SR −/− mice. These results demonstrate that NMDAR hypofunction can reproduce the numerous hippocampal deficits associated with schizophrenia, which can be reversed by chronic peripheral D-serine treatment.miR-132 | MeCP2 | glycogen synthase 3 kinase | CREB S chizophrenia is a severe psychiatric disorder that affects 1% of the population worldwide (1). There are widespread morphological, neurochemical, and functional changes in the brain in schizophrenia that have been linked to its symptomatic features (2). For example, the hippocampus of patients with schizophrenia exhibits reduced dendritic spine density (3), atrophy (4), and impaired activation while performing cognitive tasks (5). The neuroplasticity deficits observed in schizophrenia could be caused by a constellation of factors.Impaired neurotrophic signaling could be one mechanism underlying these abnormalities. BDNF regulates a complex array of processes, including neurite outgrowth and spine density, by signaling through tropomyosin receptor kinase B (TrkB), its highaffinity receptor (6). In postmortem studies, BDNF mRNA and protein (7-9) levels, as well as TrkB mRNA (7, 10, 11) and protein (12), are reduced in subjects with schizophrenia. V-akt murine thymoma viral oncogene (Akt) is a kinase downstream of TrkB. Not only is the Akt1 isoform a putative schizophrenia risk gene (13), its expression (14, 15) and the amount of phosphorylated Akt (p-Akt) (16) in the dentate gyrus (DG) are reduced in schizophrenia.Aberrant microRNA (miR) processing might also be contributing to the pathophysiology of schizophrenia (17). These noncoding RNAs regulate neural plasticity by controlling the translation of target mRNA transcripts. Expression of the neuron-enriched miR-132 is reduced in schizophrenia (18); it regulates basal and activityinduced neurite outgrowth (19), and is up-regulated in vivo in response to external stimuli (20, 21). Importantly, both BDNF (22) and miR-132 (17) expression are increased by NMDAR receptor (NMDAR) activation.Pharmacologic and biochemical evidence has converged to support NMDAR hypofunct...

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Time‐dependent involvement of the dorsal hippocampus in trace fear conditioning in mice

Cited by 162 publications

References 42 publications

Time course of dorsal and ventral hippocampal involvement in the expression of trace fear conditioning

Time course of dorsal and ventral hippocampal involvement in the expression of trace fear conditioning

Effects of Elevation of Brain Magnesium on Fear Conditioning, Fear Extinction, and Synaptic Plasticity in the Infralimbic Prefrontal Cortex and Lateral Amygdala

Multiple risk pathways for schizophrenia converge in serine racemase knockout mice, a mouse model of NMDA receptor hypofunction

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