Memory Failure
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Our topic of interest is memory failure and the various mechanisms through which memories can be purposefully erased, accidentally forgotten, or corrupted into something different. We will be working within the pathway of stabilization and de-stabilization of memory [1], also known as the modal model of memory. Each member of our group will be highlighting specific concepts related to memory encoding, consolidation, and retrieval. Since memory failure is a broad and multi-faceted topic we have divided our topic into two camps, the first dealing with how the fragility of the modal model of memory can cause changes in output behaviour, and the second dealing with how molecular manipulations can also induce deficits in memories, and even erasure.

Bibliography
1. Maren, S. (2011). Seeking a spotless mind: extinction, deconsolidation, and erasure of fear memory. Neuron, 70(5), 830-845.


False Memories

main article: False Memories
author: Emily Anne Opala

False memories, also known as confabulations, are a phenomenon in which individuals report having a memory of an event that never happened. This generally occurs due to the constructive nature of memory, where a disruption of that process will result in distortion of the memory. False memories can be significant in a clinical setting, where the production of confabulation may be evidence of underlying neurological problems, but also in a judicial setting, where a witness’ false memory of an event could have drastic consequences on the decision-making in court[1]. These memory corruptions appear to involve different brain correlates at different points in the modal model of encoding, consolidation, and retrieval, but the majority of false memory processes implicate the precuneus and the hippocampus[1]. Although the scientific community is still unsure how and why false memories occur, several theories have been proposed, including the fuzzy trace theory, the spreading activation theory, and the sensory reactivation hypothesis[1]. While these theories propose particular mechanisms for the encoding, consolidation and retrieval of false memories, it is difficult to distinguish these processes due to the nature of behavioural testing of false memories[1]. The video on the right provides an example of a false memory being implanted in an oblivious participant.

Bibliography
1. Straube B: An overview of the neuro-cognitive processes involved in the encoding, consolidation, and retrieval of true and false memories. Behavioural and Brain Functions 2012, 8(35):1-10.


Fear Memories, Stress and Reconsolidation; An Arousing Ménage à Trois

main article: Fear Memories, Stress and Reconsolidation; An Arousing Ménage à Trois
author: Matthew Tran

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The effects of the stress response on memory and cognitive function have been widely studied with great emphasis on the peripheral effects of the hormones released, including noradrenaline (NA) and glucocorticoids. For example, recent findings have implicated hippocampal glucocorticoid receptor action in the recruitment of CaMKIIa-BDNF-CREB molecular pathways [1], pathways known to mediate long-term memory formation through induction of long-term potentiation in neurons. Due to the physiological response of stress procured from fearful memories, the use of fear conditioning has been widely used as a model for studying how stress hormones are implicated within the various phases of the modal model of memory.

Under the modal model of memory, memory is said to be liable, and thus susceptible to loss and disruption, at two points: after acquisition (i.e. before consolidation) and after retrieval (i.e. before reconsolidation)[2]. The implications of reconsolidation have been speculated to be adaptive by allowing the ability to update past memories and schemas with new information[3] as well as maladaptive by potentially altering past memories causing misinformation or creation of false memories. Currently, the molecular mechanisms of reconsolidation of fear memories within the amygdala are being uncovered with recent research deeming the translational regulator mTOR [4] and the protein CREB as necessary in reconsolidation [5].

Taking into consideration the effects of stress hormone function in memory and the liable states of memory, especially during reconsolidation, the implications of systems and molecular research allow for the opportunity to perhaps disrupt and even selectively erase memories acquired during negative stressful events, specifically events which could lead to the onset of Post-Traumatic Stress Disorder (PTSD).

Bibliography
1. Chen, D. Y., Bambah-Mukku, D., Pollonini, G., & Alberini, C. M. (2012). Glucocorticoid receptors recruit the CaMKII [alpha]-BDNF-CREB pathways to mediate memory consolidation. Nature neuroscience.
2. Maren, S. (2011). Seeking a spotless mind: extinction, deconsolidation, and erasure of fear memory. Neuron, 70(5), 830-845.
3. Nader, K., & Hardt, O. (2009). A single standard for memory: the case for reconsolidation. Nature Reviews Neuroscience, 10(3), 224-234.
4. Li, Y., Meloni, E. G., Carlezon, W. A., Milad, M. R., Pitman, R. K., Nader, K., & Bolshakov, V. Y. (2013). Learning and reconsolidation implicate different synaptic mechanisms. Proceedings of the National Academy of Sciences.
5. Tronson, N. C., Wiseman, S. L., Neve, R. L., Nestler, E. J., Olausson, P., & Taylor, J. R. (2012). Distinctive roles for amygdalar CREB in reconsolidation and extinction of fear memory. Learning & Memory, 19(5), 178-181.


Functional Amnesia

main article: Functional Amnesia
author: Alexandra Mogadam

The Brittle Mind
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Le Pèlerin by René Magritte
Source: www.medicinaepersona.org [4]

Functional amnesia is an amnesic disorder, characterized by the lack of a direct biological and/or psychological mechanism of causation[1]. As a heterogeneous type of infirmity of mind and memory, functional amnesia covers a wide variety of phenotypes. The disorder usually presents itself as a type of retrograde amnesia, however can also be anterograde, usually specifically targeting episodic-autobiographical memory[1]. The loss of memory is either confined to a distinct timeframe or encompasses one’s entire autobiographical memory[1]. Both chronic as well as acute cases have been identified[1].

Even though this variety of amnesia has been recognized since the start of 19th century by the likes of Pierre Janet, not a lot of empirical scientific research has been done on the matter. For this reason a lot of the current knowledge still relies on clinical descriptions[3]. There are however a handful of scientists who have done a fair amount of research on this topic, yet interest in the field does not seems to extend beyond these few. A consequence of this is that a review of the research will present the same reoccurring names, keeping the pool of information somewhat homogeneous.

In the literature functional amnesia is mainly also known as dissociative or psychogenic amnesia, though there are slight differences in the theories underlying these terms[1]. There has been a lot of debate as to which is the most appropriate terminology for the disorder, which speaks to the general disagreement among academia regarding the etiology and mechanism of the disorder[2]. For the purposes of this page, the three terms will be discussed in conjunction to allow for a complete overview of the topic.

Bibliography
1. Markowitsch, H and Staniloiu, A. Towards solving the riddle of forgetting in functional amnesia: recent advances and current opinions. Front Psychol. 3, 1-23 (2012).
2. McKay, G. C. M., and Kopelman, M.D. Psychogenic amnesia: when memory complaints are medically unexplained. Adv.Psychiatr.Treat 15, 152–158, (2009).
3. Dell, P. Three dimensions of dissociative amnesia. J Trauma Dissociation. 14, 25-19 (2013).


Intentional and Incidental Forgetting

main article: Intentional and Incidental Forgetting
author: A Dillenburg Scur

"Undoing" memories
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source: businessweek.com

The pathway of stabilization and destabilization of memory is known as the modal model of memory. Within this pathway, there are many different steps at which memory failure can occur, including at the time of encoding information into short term memory and its subsequent consolidation into long-term memory [1]. This type of memory failure, simply referred to as forgetting, is thought to occur either by a passive decay of the memory trace, or by the active inhibition of consolidation. In the past, it was thought that intentional and incidental forgetting occurred through similar pathways. However, there has been recent evidence for a dissociation of these two types of forgetting. Current research is now focusing on elucidating the cognitive and neural differences between incidental and intentional forgetting.[2] Clarifying these differences is important in order to better understand what leads to memory success, specifically how the brain distinguishes between relevant and irrelevant information.

Bibliography
1. Maren, S. (2011). Seeking a spotless mind: extinction, deconsolidation, and erasure of fear memory. Neuron, 70(5), 830-845.
2. Rizio, A. & Dennis, N. (2013). The Neural Correlates of Cognitive Control: Successful Remembering and Intentional Forgetting. Journal of Cognitive Neuroscience, 25(2), 297-312.


Psychopharmacology and Memory Loss

main article: Psychopharmacology and Memory Loss
author: Pukhraj Grewal

Example: Flunitrazepam
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Flunitrazepam (generic name) aka Rohypnol (brand name) aka Roffies
(street name) is a majorly abused pharmaceutical, which has a wide variety of
side effects. However, the main reason for its abuse is due to its potency in
causing anterograde amnesia[2].

Pharmaceuticals have been known to cause side effects of dizziness and cognitive impairment. Many of these drugs share the common property of causing memory loss, specifically anterograde amnesia[1], through acting on the encoding phase of memory creation and retention. This is the first possible step where memory failure may occur. These drugs prevent the brain from interpreting the sensory information, which is usually received by sensory organs through the thalamus. Oddly enough, most of these drugs do not act exclusively on the thalamus; instead, there is a wide spectrum of drugs that act throughout the brain on many different types of receptors to achieve memory loss. Some major drugs, such as benzodiazepines, act on GABA receptors[1], and have different effects when combined with other pharmaceuticals[2], while others act indirectly to GABA receptors using other various pathways.

Bibliography
1. Jean-Pierre, G., & Jean-Pierre, A. (2004). Drug-Facilitated Robbery or Sexual Assault. Ther Drug Monit, 26(2), 206-210.
2. Dåderman, A. M., Fredriksson, B., Kristiansson, M., Nilsson, L., & Lidberg, L. (2002). Violent Behavior, Impulsive Decision- Making, and Anterograde Amnesia While Intoxicated With Flunitrazepam and Alcohol or Other Drugs: A Case Study in Forensic Psychiatric Patients. The journal of the American Academy of Psychiatry and the Law, 30, 238–251.


Tagged for Failure- CREB, CBP and other molecules associated with memory disruption

main article: Tagged for Failure- CREB, CBP and other molecules associated with memory disruption
author: Christopher Morrone

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Image Source: [6]

Short-term memory consolidation into long-term memory involves the strengthening of synapses. In the hippocampal CA3-CA1 pathway strengthening is LTP and NMDAR dependent. Declarative memory connections are formed and branch out for long-term maintenance starting at these synapses by transcription factors activated following a neural impulse. Herein, molecules that act to phosphorylate and activate other molecules, such as Cdk5[1], and that regulate gene expression, such as CREB and CBP[2] will be examined. Deletions in these molecules can cause deficits in memory consolidation through multiple mechanisms. cAMP response-element binding protein (CREB) is considered one of the most important molecules as a tag for the memory trace in declarative memory,[3] and there is significant research on the pathways involved in CREB activation, its effects in consolidation, and where errors can occur. Researching and understanding the molecular biology and chemistry of our brains is important in order to develop techniques to predict and treat neuropsychiatric and neurodegenerative disorders. Patients suffering from Alzheimer’s disease, which is characterized by learning and memory impairments, could benefit from treatments directed at reducing the molecular inhibition of memory, such as the BACE1 enzyme which inhibits the cAMP-PKA-CREB signaling pathway.[4] Another big topic in this field is selective memory erasure, and it may become extremely important in the removal of unwanted memories, for example in the treatment of post-traumatic stress disorders. Study and development of techniques to erase specific memories is a broadening area of research, and one paper by Han et al published in 2009 shows progress and potential.[5]

Bibliography
1. Guan, J., Su, S., Gao, J., Joseph, N., Xie, Z., Zhou, Y., Durak, O., Zhang, L., Zhu, J.J., Clauser, K.R., Carr, S.A., Tsai, L. (2011). Cdk5 is Required for Memory Function and Hippocampal Plasticity via the cAMP Signaling Pathway. PLoS ONE 6(9): e25735.
2. Barrett, R.M., Malvaez, M., Kramar, E., Matheos, D.P., Arrizon, A., Cabrera, S.M., Lynch, G., Greene, R.W., Wood, M.A. (2011). Hippocampal Focal Knockout of CBP Affects Specific Histone Modifications, Long-Term Potentiation, and Long-Term Memory. Neuropsychopharmacology. Vol. 36, p. 1545-1556.
3. Kim, J., Kwon, J., Kim, H., Han, J. (2013). CREB and neuronal selection for memory trace. Frontiers in Neural Circuits. Vol 7 (44), p. 1-7.
4. Chen, Y., Huang, X., Zhang, Y., Rockenstein, E., Bu, G., Golde, T.E., Masliah, E., Xu, H. (2012). Alzheimer’s β-secretase (BACE1) regulates the cAMP/PKA/CREB pathway independently of β-amyloid. J Neurosci. 32(33): 11390-11395.
5. Han, J., Kushner, S., Yiu, A., Hsiang, H., Buch, T., Waisman, A., Bontempi, B., Neve, R., Frankland, P., Josselyn, S. (2009). Selective Erasure of a Fear Memory. Science. Vol. 323, p. 1492-1496.



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