Rudy’s text is well-suited for the student of neuroscience and should also find an audience among constituents of peripheral fields such as pyschology or biology. The reader will be served well to have some familiarity with the underlying biochemistry, but an ample review of foundational material is provided. It manages to capture the breadth of the subject without becoming too dense. This text provides nearly a full chapter of historical context in the introduction, with additional anecdotal details peppered throughout the remainder of the book; these make for an enjoyable read. Each scientific theory is supported by published experimental findings and case studies.

• Neurobiology Of Learning And Memory Impact Factor
• The Neurobiology Of Learning And Memory Ebook
• Learning And Memory Wiki

The book strives to remain impartial in the presentation of controversial theories, providing scientific evidence and suggesting interpretations without imposing definitive conclusions when not warranted. Influential experiments and their results are described in detail and copiously illustrated. The topic of memory is covered comprehensively from a neurobiologic perspective, encompassing the full hierarchy of the brain from molecules to complete neuroanatomical structures, under the overarching topics of synaptic plasticity, molecules and memory, and memory systems.

• Neurobiology Of Learning And Memory. The Neurobiology of Learning and Memory PDF ebook. Rudy, University of Colorado. Total Download.
• Neurobiology Of Learning And Memory. The Neurobiology of Learning and Memory PDF ebook. Rudy, University of Colorado. Total Download.

The Neurobiology of Learning and Memory. Or download a FREE. In addition to being the previous chair of the neuroscience department, Prof. Rudy has taught from.

While informed by psychological insights, the book makes clear the distinction between the approaches to understanding memory taken by psychologists and neurobiologists. In Part I, the synapse is introduced as a foundational component of memory. The molecular underpinnings of synaptic plasticity are described. The central concepts of long-term potentiation and memory traces are examined, down to the minute details of relevant protein synthesis processes. Part II elucidates how molecules contribute to memory formation, consolidation, and maintenance. In this section, we learn the role of the NMDA, AMPA, and glutamate receptors in memory formation; how the amygdala and hormones such as epinephrine and the glucocorticoids might modulate memory; and memory retrieval and reconsolidation theory. Celestial air conditioning. The final part of the text moves up to the level of neural systems, focusing first on the role of the hippocampus in memory formation, segueing into the medial-temporal hippocampal system and the cortico-striatal systems.

It covers Ribot's Law, episodic memory, theories of instrumental behavior (how outcomes may modify behavior), and closes by relating fear to memory phenomena. The student or researcher who has made it their mission to understand how memory works will find this text a great resource in orienting them to the current thinking on this topic to date.

Despite the fact that extensive evidence supports the view that phases of de novo protein synthesis are necessary for memory formation and maintenance, doubts are still raised. Skeptics generally argue that amnesia and the disruption of long-term synaptic plasticity are caused by “non-specific effects” of the reagents or approaches used to disrupt protein synthesis. This paper attempts to clarify some of these issues by reviewing, discussing and providing results addressing some of the major critiques that argue against the idea that de novo protein synthesis is necessary for the stabilization of long-term memory. Introduction During the last 40 years, numerous studies have provided evidence indicating that the formation of long-term memory and long-term synaptic plasticity requires protein synthesis.

From the initial findings in the 1960s until now, hundreds of publications have reported that, in several species and a multitude of learning paradigms, a temporally limited treatment with protein synthesis inhibitors before or shortly after training produces amnesia (rev. Importantly, the same treatment at later times after training is ineffective, suggesting that memory formation depends upon an initial and temporally limited phase of protein synthesis. Moreover, even an established memory, which has become insensitive to the action of protein synthesis inhibitors can again return to a transient state of vulnerability if reactivated, for example by retrieval (rev in;; ). The temporally limited requirement of protein synthesis after training seems to parallel the initial phase of memory consolidation, a process that indicates that memory is initially in a labile state, but over time becomes stable and resilient to disruptive interferences that include, in addition to protein synthesis inhibitors, trauma, seizure, brain cooling, RNA synthesis inhibition and additional learning (rev in:;;;;;;, 1995). By analogy, because it is responsive to similar disruptive interferences, the process of re-stabilization of a memory that underwent reactivation is known as memory reconsolidation (; ).

The finding that protein synthesis is necessary for memory consolidation and reconsolidation has fundamentally influenced and shaped the research aimed at understanding the molecular bases of learning and memory during the last 40–50 years. Many questions were asked following the initial discoveries: what are the proteins required for memory formation? In which brain regions are they necessary? For how long? In which subcellular compartment of the neuron is protein synthesis essential? What is the time course of protein synthesis requirements? Experiments that have and still are in the process of addressing these questions are leading to important new levels of understanding of how memory works.

However, some issues concerning the validity of results and conclusions provided by these investigations, particularly those obtained with protein synthesis inhibitors, have been and continue to be the object of recurrent debates. Some authors still question whether protein synthesis is truly essential during memory consolidation and reconsolidation, and generally put forward two main critiques. First, they propose that the amnesia produced by protein synthesis inhibitors is a result of “side effects” rather than inhibition of protein synthesis per se.

Second, because in some cases the amnesia was found to be transient, and memory recovered after some time, some investigators hypothesize that the inhibitors’ effects target memory retrieval processes rather than memory consolidation or storage. Here, I will attempt to revisit, and hopefully help clarifying these two issues by discussing what it is known about the protein synthesis inhibitors “side effects“ and the effect of time on protein synthesis inhibition. I will also comment on additional evidence that, in my view, support the hypothesis that protein synthesis is indeed essential for memory consolidation and reconsolidation.

Neurobiology Of Learning And Memory Impact Factor

The role of protein synthesis in long-term synaptic plasticity and memory: evidence from molecular-targeting approaches Notably, other molecular approaches have confirmed that the synthesis of proteins is an essential molecular step of memory formation. One strategy utilized to selectively block the synthesis of specific proteins is the delivery of antisense sequences or the expression of dominant negative molecules (e.g.;;;;;;;;; ). The antisense as well as small interfering RNA (siRNA) methods inhibit the translation of specifically targeted mRNAs. Moreover, in the brain, these strategies allow the investigator to target gene regulation in an anatomically and temporally restricted fashion. The antisense technology has been studied for almost 30 years. The mechanisms of action, stability, specificity and delivery issues have been largely investigated and a great deal is now known about the use of antisense sequences in vivo (;; ). The effect of the antisense treatment compared to relative controls, including sequences containing the same base composition but in scrambled order which are not complementary to any known RNA sequences, indicates that the ongoing expression of the corresponding protein is critical for the function tested (e.g.

The Neurobiology Of Learning And Memory Ebook

More than 100 papers have reported significant effects of antisense sequences during memory consolidation, memory reconsolidation, long-term synaptic plasticity or brain long-term changes in general. Among the proteins targeted, there are transcription factors such as CREB, C/EBP, zif 268, fos, nur 77, neurotransmitter receptors, such as NR1 and alpha7 acethylcholine receptors, growth factors such as BDNF and many other molecules including arc, APP and SNAP-25. Challenge the conclusion that the synthesis of specific molecules is required for memory formation, and suggest that the effect of antisense sequences on memory retention might be related to a consequent rebound from the antisense-induced inhibition of protein expression, which in some case has been documented. To my knowledge, the rebound was described only in this one case. Nevertheless, if this explanation is true, it would imply that the translation during the rebound phase is necessary for memory formation. Hence, although in a more indirect fashion, such outcome would still support the critical role of protein translation during memory formation. Furthermore, results similar to those obtained with antisense sequences have been reported using several other approaches including temporally-regulated expression of dominant negative molecules (; ), interfering decoys (e.g.;;;; ) or blocking antibodies (; ).

Given the consistency of the findings with different molecular blocking approaches and the high number of different molecules targeted, it is reasonable to conclude that it is the blocking effect that unravels the biosynthestic molecular requirements for memory formation. Additional support to this conclusion is offered by the observations that, in numerous studies, changes in the profiles of gene and protein expression has been documented (;;;;; ) and the functional requirement of specific proteins during long-term memory or long-term synaptic plasticity formation is accompanied by a transient increase in their mRNA and/or protein expression. This has been particularly evident and characterized in the case of regulatory IEGs.

Such an outcome, precisely because it concerns inducible transcription factors, whose function is to regulate the expression of target genes, strengthen the conclusion that phases of increased gene expression are coupled to learning events. For example, using a decoy oligodeoxynucleotide that interferes with its DNA binding activity, we have shown that in the invertebrate Aplysia californica, the transcription factor CCAAT enhancer binding protein (C/EBP) is required for up to 9, but not 12 hours after the induction of long-term facilitation. Importantly, the requirement for C/EBP during Aplysia long-term facilitation was also confirmed using two additional approaches: antisense-mediated knock-down and antibodies that were shown to functionally block the DNA binding activity of C/EBP. Moreover, in rat hippocampus, we found that C/EBPbeta is induced starting at 9 hours after inhibitory avoidance training, remains increased at 20 and 28 hours after training and returns to control levels at 48 hours after training. The functional requirement of hippocampal C/EBPbeta parallels its profile of learning-related expression increase, as in fact antisense-mediated knock-down of C/EBPbeta in the hippocampi blocks memory consolidation at 5 and 24 hours after training but not 1 hour before or 46 hours after training.

These results frame the temporally-limited expression regulation and functional requirement of hippocampal C/EBPbeta during the consolidation phase of memory, suggesting that a cascade of gene expression is initiated by learning and remains active for more than 24 hours after training. This cascade of molecular events is therefore a critical molecular step for the establishment of long-lasting memories.

C/EBPbeta antisense blocks long-term memory consolidation. ( a) Injection, training and testing time points.

( b) IA acquisition (Acq) and memory retention of unoperated rats. Retention was assessed 48 h after training by measuring the latency to reenter. Another set of evidence that also supports the conclusion that protein synthesis is critical for memory formation is the discovery that intact functional components of the translational machinery are critical for long-term memory and synaptic plasticity (;;;; ). For example, a recent study show that phosphorylation-dependent regulation of the Initiation Factor 2 α (eIF2α) is a critical hub for the control of synaptic plasticity and memory.

EIF2α is an initiation factor of translation, thus it controls the overall rate of protein synthesis through its effects on the translation machinery. In addition to this general effect, eIF2α also controls the rate of translation of specific proteins, including that of the transcriptional repressor ATF4, an antagonist of CREB-mediated gene transcription. Recently reported that hippocampal synaptic plasticity, associative fear conditioning, spatial learning and memory, and novel taste memory require the function of eIF2a, which is regulated through its phosphorylation.

Specifically, they demonstrated that eIF2α dephosphorylation at serine 51 is associated with augmented memory for spatial navigation, Pavlovian fear conditioning and conditioned taste aversion. These results underline the importance of activity-induced protein translation during long-term synaptic plasticity and memory. Thus, it is consistent with a multitude of controlled experiments to conclude that protein synthesis is required for long-term synaptic plasticity and memory formation. In my view, the question that remains to be addressed is not if but how protein synthesis allows long-term memory and plasticity to occur.

Learning And Memory Wiki

The relevant questions are numerous: Is synaptic vs cell body protein synthesis more or less critical? What is the temporal profile of the critical phase/s of protein synthesis? Does it target specific neurons and synapses and how? What is the role of this protein synthesis? Does it refill the homeostatic pool at activated synapses? Does modulation contribute to the protein synthesis-dependent changes of memory consolidation? All these very important questions are under investigation (e.g.;;;;; ) and beyond the scope of this review, and likely to be addressed in the near future.

Requirement for protein synthesis during memory formation: temporary or persistent effect? Because inhibitors of protein synthesis in some cases have caused only temporary amnesia, and the memory can spontaneously recovers after some time, it has been questioned whether the effect of these treatments targets memory retrieval rather than consolidation or reconsolidation processes (e.g.;;;;; ). However, opposite results have been reported in other cases, in which the memory deficits observed after the administration of protein synthesis inhibitors were persistent (e.g.;;; ), and, furthermore, the experience of a reminder failed to restore memory retention (e.g.;;; ).

The reader should refer to an excellent, exhaustive and updated discussion of this matter. Here, I will comment on some additional evidence that can explain the opposite outcomes on the duration of amnesia after translation inhibition. One aspect that is unfortunately often neglected in experiments using protein synthesis inhibitors in learning and memory is the parallel accurate assessment of the degree and duration of protein synthesis inhibition.

Very few authors studying memory or plasticity have also reported the rate of protein synthesis inhibition in their experiments, and often use references describing inhibition of protein synthesis in different brain areas and under different experimental conditions as general principles. However, it is critical that, as detailed above, the effect of protein synthesis inhibitors be assessed in each experimental model, as variations of protein synthesis occur in relation to dosage, route of administration, brain areas, behavioral protocols, etc. Studies carried out in the 1970s proved that stronger memories require longer (stronger) inhibition of protein synthesis to be permanently disrupted, suggesting that, in fact, a partial inhibition may exactly be the reason why a transient amnesia can be seen (;;; ). In agreement, a recent work from my laboratory has demonstrated that a partial inhibition of protein synthesis during the consolidation or reconsolidation phase precisely results in temporary behavioral impairments that recover at later times.

However, a more prolonged inhibition led to a persistent disruption of the behavioral response. In this study, we assessed the effect of two widely used protein synthesis inhibitors, anisomycin and cycloheximide on the formation of conditioned place preference to morphine (mCPP). The two inhibitors, which block protein synthesis by distinct mechanisms, were used in order to confirm that the results were specifically related to protein synthesis inhibition and not to unspecific effects. Both inhibitors produced similar outcomes.

Rats were conditioned to morphine or vehicle once a day for four days, and at the end of a four-day conditioning session, half of the morphine-conditioned rats received a single peripheral injection of either anisomycin or cycloheximide while the other half received vehicle solution. CPP was tested 24 hours later. Both inhibitors significantly blocked mCPP. To determine whether the effect was stable, the animals were retested 1 week later. At this time, the animals showed a partial, but significant recovery of the place preference, suggesting that that inhibition of protein synthesis at the end of conditioning impaired CPP only transiently.

Protein synthesis is required for the induction of mCPP. A– C, Values are expressed as mean ± SEM time spent in the drug-conditioned chamber. An established mCPP is disrupted by protein synthesis inhibitors administered after a single conditioning session. A– D, Values are expressed as mean ± SEM time spent in the drug-conditioned chamber. Conclusions Numerous studies provide strong evidence that the expression of specific proteins during an early and temporally limited phase after learning is necessary for the stabilization or consolidation of long-term memory and synaptic plasticity. Although this conclusion is still sometimes challenged with arguments of potential non-specific effects, a number of different approaches that include the use of a variety of inhibitors of protein synthesis, antisense sequences, regulated expression of dominant negative molecules, blocking antibodies, identification of gene expression profiles and detailed investigations of the mechanisms of translation activated by learning or memory reactivation, all seem to converge on the concept that protein synthesis plays an essential role in the stabilization of both new and reactivated memories.

The functional processes that this protein synthesis subserves during memory consolidation and storage still remain to be understood, and their understanding is the object of existing investigations. Many thanks to Bob Blitzer, Deanna Benson for their helpful comments. Thanks to all the members of my lab for their invaluable contribution to the work discussed and for their helpful feedbacks on the manuscript and to Dr. Reginald Miller and the CCMS facility of Mount Sinai for technical support. The work included in this review was supported by the National Institute of Mental Health (R01 MH65635, R01 MH074736), National Institute of Drugs of Abuse (R21 CEBRA DA017672) and Hirschl Foundation to CMA.