Spaced initial stimulus familiarization enhances novelty preference in Long-Evans rats

Anderson, Matthew; Jablonski, Sarah A.; Klimas, Diana B.

doi:10.1016/j.beproc.2008.02.005

Cited by 26 publications

(26 citation statements)

References 19 publications

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“…Other studies using variable stimulation intensities suggest that additional potentiation can be induced four hours after induction of LTP1 (10,12). In all, the present results show that LTP has a previously undetected refractory period, lasting for 30-60 min, which creates an analog of the behavioral spaced trials effect (13).…”

Section: Resultssupporting

confidence: 59%

Synaptic evidence for the efficacy of spaced learning

Kramár¹,

Babayan²,

Gavin

et al. 2012

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

148

189

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The superiority of spaced vs. massed training is a fundamental feature of learning. Here, we describe unanticipated timing rules for the production of long-term potentiation (LTP) in adult rat hippocampal slices that can account for one temporal segment of the spaced trials phenomenon. Successive bouts of naturalistic theta burst stimulation of field CA1 afferents markedly enhanced previously saturated LTP if spaced apart by 1 h or longer, but were without effect when shorter intervals were used. Analyses of Factin-enriched spines to identify potentiated synapses indicated that the added LTP obtained with delayed theta trains involved recruitment of synapses that were "missed" by the first stimulation bout. Single spine glutamate-uncaging experiments confirmed that less than half of the spines in adult hippocampus are primed to undergo plasticity under baseline conditions, suggesting that intrinsic variability among individual synapses imposes a repetitive presentation requirement for maximizing the percentage of potentiated connections. We propose that a combination of local diffusion from initially modified spines coupled with much later membrane insertion events dictate that the repetitions be widely spaced. Thus, the synaptic mechanisms described here provide a neurobiological explanation for one component of a poorly understood, ubiquitous aspect of learning.A n extensive body of experimental work indicates that periodic exposure to the same material results in better retention than a single "cramming" session. Although this distributed practice effect was first recognized in late 19th century (1-3), and has since been the subject of a very large psychological literature (4), the neurobiological processes that give rise to the phenomenon are poorly understood. Activity-dependent synaptic plasticity, and, in particular, long-term potentiation (LTP) of glutamatergic transmission, is thought to underlie rapid storage of new information (5, 6). Therefore, it is surprising that little experimental attention has been given to the possibility that specialized features of LTP may contribute to the spaced trials (distributed practice) effect. This likely reflects the lack of data indicating that the substrates of the potentiation effect include properties that are engaged, or enhanced, only by widely spaced stimulation episodes. Specifically, several types of studies point to the conclusion that the elaborate processes yielding fully developed LTP reach completion within 10-15 min (5, 7, 8); these findings do not include results suggestive of a delayed capacity for triggering additional changes to already potentiated synapses. There is considerable evidence for a later LTP stabilization step involving protein synthesis (9), but the effects of this on subsequent plasticity involve inputs other than those already expressing potentiation (10).Here, we describe a set of mechanisms and timing rules in hippocampus that result in widely spaced episodes of theta burst stimulation (TBS) generating a much greater degree of LT...

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Section: Resultssupporting

confidence: 59%

Synaptic evidence for the efficacy of spaced learning

Kramár¹,

Babayan²,

Gavin

et al. 2012

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

148

189

View full text Add to dashboard Cite

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“…Whatever its origins, the memory impairment in Fmr1 KO mice was corrected by spaced training, a well-described process in which brief, temporally separated training episodes are used to enhance memory (9,25,35,36). The studies also demonstrate that the facilitating effects of spacing, for both genotypes, align with the periodicity of afferent stimulation required to enhance hippocampal LTP (10,17).…”

Section: Discussionmentioning

confidence: 76%

Spaced training rescues memory and ERK1/2 signaling in fragile X syndrome model mice

Seese

Wang

Yao

et al. 2014

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

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Recent studies have shown that short, spaced trains of afferent stimulation produce much greater long-term potentiation (LTP) than that obtained with a single, prolonged stimulation episode. The present studies demonstrate that spaced training regimens, based on these LTP timing rules, facilitate learning in wild-type (WT) mice and can offset learning and synaptic signaling impairments in the fragile X mental retardation 1 (Fmr1) knockout (KO) model of fragile X syndrome. We determined that 5 min of continuous training supports object location memory (OLM) in WT but not Fmr1 KO mice. However, the same amount of training distributed across three short trials, spaced by one hour, produced robust long-term memory in the KOs. At least three training trials were needed to realize the benefit of spacing, and intertrial intervals shorter or longer than 60 min were ineffective. Multiple short training trials also rescued novel object recognition in Fmr1 KOs. The spacing effect was surprisingly potent: just 1 min of OLM training, distributed across three trials, supported robust memory in both genotypes. Spacing also rescued training-induced activation of synaptic ERK1/2 in dorsal hippocampus of Fmr1 KO mice. These results show that a spaced training regimen designed to maximize synaptic potentiation facilitates recognition memory in WT mice and can offset synaptic signaling and memory impairments in a model of congenital intellectual disability.Fmr1 KO | hippocampus | object location memory | massed training | novel object recognition F ragile X syndrome (FXS) is the most common cause of inherited intellectual disability (ID) (1). Currently no treatments exist for cognitive deficits associated with FXS or other neurodevelopmental disorders with ID. Research on the fragile X mental retardation 1 (Fmr1) KO mouse model of FXS has identified impairments in synaptic signaling required to produce lasting synaptic modifications (2-6) with corresponding disturbances in the activation threshold and stabilization of hippocampal long-term potentiation (LTP) (7,8). These findings suggest specific synaptic disturbances underlie learning problems in FXS as well as targets for therapeutic interventions to improve cognitive function.The present experiments tested predictions from LTP studies as to how modified training paradigms might rescue synaptic signaling and learning in Fmr1 KO mice. There is a deep literature demonstrating that individuals learn better when trained in short trials spaced in time than in a single, extended training episode (9). We recently found that LTP exhibits a synaptic analog for this "spaced trials effect" (10). Specifically, in hippocampal field CA1 short trains of theta burst afferent stimulation spaced by 60 min elicit far greater synaptic potentiation than can be achieved with long theta trains or by repeated trains applied at shorter intervals. As LTP is considered a mechanism of memory encoding, we propose that spaced training regimens that use the same 60-min periodicity should facilitate hippocampus...

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“…Por un lado incluye la respuesta a la novedad, activación, factores que se relacionan con el estrés y por otro lado, una respuesta que disminuye cuando el ambiente se vuelve familiar, lo cual requiere procesos relacionados con el aprendizaje, el recuerdo y el reconocimiento (Thiel, Huston & Schwarting, 1998). Además, múl-tiples estudios han mostrado que los animales prefieren explorar objetos novedosos, en comparación con aquellos con los que tuvieron una experiencia previa (Anderson, Jablonski & Klimas, 2008).…”

Section: Introductionunclassified

“…El estudio de los factores que influyen en las reacciones frente a la novedad, así como los mecanismos involucrados en este proce -so, resultan de gran importancia dado que se ha demostrado que la capacidad para responder a estímulos novedosos está relacionada con la autoadministración de variadas drogas, el descubrimiento de tumores espontáneos e incluso la expectativa de vida, ya que se comprobó que animales neofóbicos mue ren más jóvenes que sus contrapartes neofílicos (Anderson et al, 2008). El reporte de este ti po de estudios permite sentar las bases para el desarrollo de posibles estudios aplicados así como futuras investigaciones, las cuales no pueden darse sin un adecuado conocimiento de esos mecanismos.…”

Section: Introductionunclassified

Novedad y modulación de la memoria: Mecanismos neurobiológicos implicados

Justel

Psyrdellis

2014

Interd

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RESUMENLa exposición a estímulos novedosos es un protocolo simple de emplear que involucra múl-tiples sistemas y procesos de memoria tales como codificación, consolidación y recuperación de la información. Esto hace plausible de emplearlo como un tratamiento útil para estudiar los mecanismos comportamentales, fisiológicos y moleculares implicados en esta función cognitiva. Se presentan estudios en modelos animales que dan cuenta de cómo la exploración de un ambiente novedoso puede ser útil para mejorar o deteriorar la memoria, en diferentes períodos ontogenéticos. Además, se presentan investigaciones que demuestran la participación de los diversos sistemas de neurotransmisión en este fenómeno así como los mecanismos moleculares implicados en este tipo de tratamiento. De este modo este tipo de tratamiento, no invasivo y sencillo de aplicar, adquiere relevancia para la ciencia aplicada como una posible alternativa para el desarrollo de estrategias de intervención en la temá-tica.Palabras clave: Novedad; Memoria; Neurotransmisión; Mecanismos moleculares. ABSTRACTExposure to novel stimuli is a simple procedure to use that involved several systems and memory processes, such as acquisition, consolidation and recall of the information. Which make it a possible treatment to study the behavioral, physiological and molecular mechanism involved in this cog nitive function. Novelty detection plays an important role in adaptation to the environmental changes and in the avoidance of possible dangerous. A novel stimulus elicits a response that will produce habituation when it becomes familiar. When animals are first exposed to a novel environment they explore it actively and in parallel they compare it to previous experiences, stored in its memory to evaluate the degree of novelty. On one side, it includes the response to novelty, activation, and stress-related factors and on the other hand, a response that decreases as the environment becomes familiar, which requires different processes related to learning, recall and recognition. Also, multiple studies showed that animals prefer to explore novel objects, compared with those with whom they had previous experience. Moreover, it has been shown that the ability to respond to novel stimuli is related to self-administration of various

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Spaced initial stimulus familiarization enhances novelty preference in Long-Evans rats

Cited by 26 publications

References 19 publications

Synaptic evidence for the efficacy of spaced learning

Synaptic evidence for the efficacy of spaced learning

Spaced training rescues memory and ERK1/2 signaling in fragile X syndrome model mice

Novedad y modulación de la memoria: Mecanismos neurobiológicos implicados

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