Overtraining Strengthens the Visual Discrimination Memory Trace Outside the Hippocampus in Male Rats

Frontiers in Behavioral Neuroscience ◽

10.3389/fnbeh.2021.768552 ◽

2021 ◽

Vol 15 ◽

Author(s):

Hugo Lehmann ◽

Morgan G. Stykel ◽

Melissa J. Glenn

Keyword(s):

Retrograde Amnesia ◽

Visual Discrimination ◽

Memory Trace ◽

Memory Systems ◽

Male Rats ◽

Hippocampal Damage ◽

Extensive Damage

The hippocampus (HPC) may compete with other memory systems when establishing a representation, a process termed overshadowing. However, this overshadowing may be mitigated by repeated learning episodes, making a memory resistant to post-training hippocampal damage. In the current study, we examined this overshadowing process for a hippocampal-dependent visual discrimination memory in rats. In Experiment 1, male rats were trained to criterion (80% accuracy on two consecutive days) on a visual discrimination and then given 50 additional trials distributed over 5 days or 10 weeks. Regardless of this additional learning, extensive damage to the HPC caused retrograde amnesia for the visual discrimination, suggesting that the memory remained hippocampal-dependent. In Experiment 2, rats received hippocampal damage before learning and required approximately twice as many trials to acquire the visual discrimination as control rats, suggesting that, when the overshadowing or competition is removed, the non-hippocampal memory systems only slowly acquires the discrimination. In Experiment 3, increasing the additional learning beyond criterion by 230 trials, the amount needed in Experiment 2 to train the non-hippocampal systems in absence of competition, successfully prevented the retrograde amnesic effects of post-training hippocampal damage. Combined, the findings suggest that a visual discrimination memory trace can be strengthened in non-hippocampal systems with overtraining and become independent of the HPC.

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d-Serine alleviates retrograde amnesia of a visual discrimination task in rats with a lesion of the perirhinal cortex

Brain Research ◽

10.1016/s0006-8993(03)02894-4 ◽

2003 ◽

Vol 979 (1-2) ◽

pp. 240-244 ◽

Cited By ~ 11

Author(s):

Jannike M. Andersen ◽

Frode Fonnum ◽

Trond Myhrer

Keyword(s):

Retrograde Amnesia ◽

Visual Discrimination ◽

Discrimination Task ◽

Perirhinal Cortex ◽

Visual Discrimination Task

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Cadmium Chloride Induces Memory Deficits and Hippocampal Damage by Activating the JNK/p66Shc/NADPH Oxidase Axis

International Journal of Toxicology ◽

10.1177/1091581820930651 ◽

2020 ◽

Vol 39 (5) ◽

pp. 477-490

Author(s):

Attalla Farag El-kott ◽

Ali S. Alshehri ◽

Heba S. Khalifa ◽

Abd-El-karim M. Abd-Lateif ◽

Mohammad Ali Alshehri ◽

...

Keyword(s):

Nadph Oxidase ◽

Cadmium Chloride ◽

Nicotinamide Adenine Dinucleotide Phosphate ◽

Male Rats ◽

Hippocampal Damage ◽

Vitro Experiment ◽

In Vitro Experiment ◽

In Vivo Experiment

This study investigated whether the mechanism underlying the neurotoxic effects of cadmium chloride (CdCl2) in rats involves p66Shc. This study comprised an initial in vivo experiment followed by an in vitro experiment. For the in vivo experiment, male rats were orally administered saline (vehicle) or CdCl2 (0.05 mg/kg) for 30 days. Thereafter, spatial and retention memory of rats were tested and their hippocampi were used for biochemical and molecular analyses. For the in vitro experiment, control or p66Shc-deficient hippocampal cells were treated with CdCl2 (25 µM) in the presence or absence of SP600125, a c-Jun N-terminal kinase (JNK) inhibitor. Cadmium chloride impaired the spatial learning and retention memory of rats; depleted levels of glutathione and manganese superoxide dismutase; increased reactive oxygen species (ROS), tumor necrosis factor α, and interleukin 6; and induced nuclear factor kappa B activation. Cadmium chloride also decreased the number of pyramidal cells in the CA1 region and induced severe damage to the mitochondria and endoplasmic reticulum of cells in the hippocampi of rats. Moreover, CdCl2 increased the total unphosphorylated p66Shc, phosphorylated (Ser36) p66Shc, phosphorylated JNK, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, cytochrome c, and cleaved caspase-3. A dose–response increase in cell death, ROS, DNA damage, p66Shc, and NADPH oxidase was also observed in cultured hippocampal cells treated with CdCl2. Of note, all of these biochemical changes were attenuated by silencing p66Shc or inhibiting JNK with SP600125. In conclusion, CdCl2 induces hippocampal ROS generation and apoptosis by promoting the JNK-mediated activation of p66Shc.

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Retrograde amnesia after hippocampal damage: Recent vs. remote memories in two tasks

Hippocampus ◽

10.1002/1098-1063(2001)11:1<27::aid-hipo1017>3.0.co;2-4 ◽

2001 ◽

Vol 11 (1) ◽

pp. 27-42 ◽

Cited By ~ 104

Author(s):

Robert J. Sutherland ◽

Michael P. Weisend ◽

Dave Mumby ◽

Robert S. Astur ◽

Faith M. Hanlon ◽

...

Keyword(s):

Retrograde Amnesia ◽

Hippocampal Damage

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Do infants retain the statistics of a statistical learning experience? Insights from a developmental cognitive neuroscience perspective

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2016.0054 ◽

2017 ◽

Vol 372 (1711) ◽

pp. 20160054 ◽

Cited By ~ 15

Author(s):

Rebecca L. Gómez

Keyword(s):

Adult Learners ◽

Statistical Learning ◽

Memory Trace ◽

Learning Experience ◽

Memory Systems ◽

Human Infants ◽

Critical Gap ◽

Knowledge Of Language ◽

Long Term Retention

Statistical structure abounds in language. Human infants show a striking capacity for using statistical learning (SL) to extract regularities in their linguistic environments, a process thought to bootstrap their knowledge of language. Critically, studies of SL test infants in the minutes immediately following familiarization, but long-term retention unfolds over hours and days, with almost no work investigating retention of SL. This creates a critical gap in the literature given that we know little about how single or multiple SL experiences translate into permanent knowledge. Furthermore, different memory systems with vastly different encoding and retention profiles emerge at different points in development, with the underlying memory system dictating the fidelity of the memory trace hours later. I describe the scant literature on retention of SL, the learning and retention properties of memory systems as they apply to SL, and the development of these memory systems. I propose that different memory systems support retention of SL in infant and adult learners, suggesting an explanation for the slow pace of natural language acquisition in infancy. I discuss the implications of developing memory systems for SL and suggest that we exercise caution in extrapolating from adult to infant properties of SL. This article is part of the themed issue ‘New frontiers for statistical learning in the cognitive sciences’.

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Temporally Graded Retrograde Amnesia of Contextual Fear after Hippocampal Damage in Rats: Within-Subjects Examination

Journal of Neuroscience ◽

10.1523/jneurosci.19-03-01106.1999 ◽

1999 ◽

Vol 19 (3) ◽

pp. 1106-1114 ◽

Cited By ~ 373

Author(s):

Stephan G. Anagnostaras ◽

Stephen Maren ◽

Michael S. Fanselow

Keyword(s):

Retrograde Amnesia ◽

Hippocampal Damage ◽

Contextual Fear ◽

Within Subjects

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Hippocampus-sensitive and striatum-sensitive learning one month after morphine or cocaine exposure in male rats

10.1101/2021.11.07.467628 ◽

2021 ◽

Author(s):

Robert S Gardner ◽

Donna L Korol ◽

Paul E Gold

Keyword(s):

Drug Exposure ◽

Drugs Of Abuse ◽

Glycogen Synthase ◽

Memory Systems ◽

Male Rats ◽

Cocaine Exposure ◽

Downstream Target ◽

Protein Levels ◽

Hippocampal Astrocytes ◽

Response Task

These experiments examined whether exposure to drugs of abuse altered the balance between hippocampal and striatal memory systems as measured long after drug treatments. Male rats received injections of morphine (5 mg/kg), cocaine (20 mg/kg), or saline for five consecutive days. One month later, rats were then trained to find food on a hippocampus-sensitive place task or a striatum-sensitive response task. Relative to saline controls, morphine-treated rats exhibited impaired place learning but enhanced response learning; prior cocaine exposure did not significantly alter learning on either task. Another set of rats was trained on a dual-solution T-maze that can be solved with either place or response strategies. While a majority (67%) of control rats used place solutions in this task, morphine treatment one month prior resulted in a shift to response solutions exclusively (100%). Prior cocaine treatment did not significantly alter strategy selection. Molecular markers related to learning and drug abuse were measured in the hippocampus and striatum one month after drug exposure in behaviorally untested rats. Protein levels of glial-fibrillary acidic protein (GFAP), an intermediate filament specific to astrocytes, increased significantly in the hippocampus after morphine, but not after cocaine exposure. Exposure to morphine or cocaine did not significantly change levels of brain-derived neurotrophic factor (BDNF) or a downstream target of BDNF signaling, glycogen synthase kinase 3β (GSK3β), in the hippocampus or striatum. Thus, exposure to morphine results in a long-lasting shift from hippocampal toward striatal dominance during learning. The effects of prior morphine injections on GFAP suggest that long-lasting alterations in hippocampal astrocytes may be associated with these behavioral strategy shifts.

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Lateral entorhinal cortex suppresses drift in cortical memory representations.

10.1101/2021.11.04.467279 ◽

2021 ◽

Author(s):

Maryna Pilkiw ◽

Justin Jarovi ◽

Kaori Takehara-Nishiuchi

Keyword(s):

Entorhinal Cortex ◽

Memory Retrieval ◽

Firing Pattern ◽

Memory Trace ◽

Male Rats ◽

Memory Representations ◽

Familiar Environment ◽

Functional Relevance ◽

The Stability ◽

Cortical Representations

Memory retrieval is thought to depend on the reinstatement of cortical memory representations guided by pattern completion processes in the hippocampus. The lateral entorhinal cortex (LEC) is one of the intermediary regions supporting hippocampal-cortical interactions and houses neurons that prospectively signal past events in a familiar environment. To investigate the functional relevance of the LEC's activity for cortical reinstatement, we pharmacologically inhibited the LEC and examined its impact on the stability of ensemble firing patterns in one of the LEC's efferent targets, the medial prefrontal cortex (mPFC). When male rats underwent multiple epochs of identical stimulus sequences in the same environment, the mPFC maintained a stable ensemble firing pattern across repetitions, particularly when the sequence included pairings of neutral and aversive stimuli. With LEC inhibition, the mPFC still formed an ensemble pattern that accurately captured stimuli and their associations within each epoch. However, LEC inhibition markedly disrupted its consistency across the epochs by decreasing the proportion of mPFC neurons that stably maintained firing selectivity for stimulus associations. Thus, the LEC stabilizes cortical representations of learned stimulus associations, thereby facilitating the recovery of the original memory trace without generating a new, redundant trace for familiar experiences. Failure of this process might underlie retrieval deficits in conditions associated with degeneration of the LEC, such as normal aging and Alzheimer's disease.

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