Noradrenergic activation of the basolateral amygdala facilitates memory specificity for similar events experienced close in time

Nature Neuroscience · 2025-07-23 · 4 citations

Identification of a unique, <i>de novo MYCBP2</i> variant in an individual with highly superior autobiographical memory

medRxiv · 2024-12-20 · 1 citations

Abstract Highly Superior Autobiographical Memory (HSAM) is an extremely rare condition characterized by an individual’s unparallelled ability to recall personal past events with exceptional detail and accuracy, including exact dates and days of the week, spanning many decades 1–3 . The molecular underpinnings of HSAM are unknown. Here, we investigated an individual with HSAM through neuropsychological testing, structural brain imaging, and genetic analyses. HSAM was confirmed as an isolated exceptional cognitive ability, with brain imaging revealing exceptionally large volumes of regions within the hippocampal formation, which have been previously linked to autobiographical memory. Using whole exome sequencing of the HSAM individual and their unaffected parents, we identified a unique de novo missense variant in MYCBP2 , which encodes an E3 ubiquitin-protein ligase 4,5 . To explore the potential behavioral consequences of this variant, we introduced the homologous variant into C. elegans , which resulted in reduced forgetting and increased membrane-bound glutamate receptor in relevant neuronal cells. These findings show that the studied HSAM individual carries a unique, de novo missense variant in MYCBP2 , which reduces forgetting in a model organism. The identification of functionally relevant genetic variants in individuals with superior memory traits has the potential to inform future research into memory-modulating therapies.

Editorial

Neuroscience · 2022-07-30

Glucocorticoid effects on working memory impairment require l-type calcium channel activity within prefrontal cortex

Neurobiology of Learning and Memory · 2022-11-18 · 8 citations

Previous findings have indicated that glucocorticoid hormones impair working memory via an interaction with the β-adrenoceptor-cAMP signaling cascade to rapidly increase cAMP-dependent protein kinase (PKA) activity within the prefrontal cortex (PFC). However, it remains elusive how such activation of PKA can affect downstream cellular mechanisms in regulating PFC cognitive function. PKA is known to activate l-type voltage-gated Ca2+ channels (LTCCs) which regulate a broad range of cellular processes, including neuronal excitability and neurotransmitter release. The present experiments examined whether LTCC activity within the PFC is required in mediating glucocorticoid and PKA effects on spatial working memory. Male Sprague Dawley rats received bilateral administration of the LTCC inhibitor diltiazem together with either the glucocorticoid receptor agonist RU 28362 or PKA activator Sp-cAMPS into the PFC before testing on a delayed alternation task in a T-maze. Both RU 28362 and Sp-cAMPS impaired working memory, whereas the LTCC inhibitor diltiazem fully blocked the working memory impairment induced by either RU 28362 or Sp-cAMPS. Conversely, bilateral administration of the LTCC agonist Bay K8644 into the PFC was sufficient to impair working memory. Thus, these findings provide support for the view that glucocorticoids, via an interaction with the β-adrenergic signaling cascade and enhanced PKA activity levels, impair working memory by increasing LTCC activity in the PFC.

The Entorhinal Cortex as a Gateway for Amygdala Influences on Memory Consolidation

Neuroscience · 2022 · 49 citations

• Neuroscience
• Psychology

Basolateral amygdala activation enhances object recognition memory by inhibiting anterior insular cortex activity

Proceedings of the National Academy of Sciences · 2022 · 27 citations

• Neuroscience
• Psychology
• Chemistry

Noradrenergic activation of the basolateral amygdala (BLA) by emotional arousal enhances different forms of recognition memory via functional interactions with the insular cortex (IC). Human neuroimaging studies have revealed that the anterior IC (aIC), as part of the salience network, is dynamically regulated during arousing situations. Emotional stimulation first rapidly increases aIC activity but suppresses it in a delayed fashion. Here, we investigated in male Sprague-Dawley rats whether the BLA influence on recognition memory is associated with an increase or suppression of aIC activity during the postlearning consolidation period. We first employed anterograde and retrograde viral tracing and found that the BLA sends dense monosynaptic projections to the aIC. Memory-enhancing norepinephrine administration into the BLA following an object training experience suppressed aIC activity 1 h later, as determined by a reduced expression of the phosphorylated form of the transcription factor cAMP response element-binding (pCREB) protein and neuronal activity marker c-Fos. In contrast, the number of perisomatic γ-aminobutyric acid (GABA)ergic inhibitory synapses per pCREB-positive neuron was significantly increased, suggesting a dynamic up-regulation of GABAergic tone. In support of this possibility, pharmacological inhibition of aIC activity with a GABAergic agonist during consolidation enhanced object recognition memory. Norepinephrine administration into the BLA did not affect neuronal activity within the posterior IC, which receives sparse innervation from the BLA. The evidence that noradrenergic activation of the BLA enhances the consolidation of object recognition memory via a mechanism involving a suppression of aIC activity provides insight into the broader brain network dynamics underlying emotional regulation of memory.

<i>NTRK2</i> methylation is related to reduced PTSD risk in two African cohorts of trauma survivors

Proceedings of the National Academy of Sciences · 2020-08-17 · 17 citations

Significance In the present study we investigated the epigenetic pattern of genes involved in the regulation of glucocorticoid receptor signaling in two African populations of heavily traumatized individuals. The strongest link between regional methylation and posttraumatic stress disorder (PTSD) risk and symptoms was observed for NTRK2 , which has been shown to play an important role in memory formation. NTRK2 methylation was not related to trauma load, suggesting that methylation differences preexisted the trauma. Furthermore, NTRK2 methylation was found to be related to memory and memory-related brain activity in healthy nontraumatized individuals. The present findings suggest that epigenetic modifications of NTRK2 are involved in memory modulation in health, and in influencing risk and symptoms of PTSD in case of traumatic experiences.

Bed nuclei of the stria terminalis modulate memory consolidation via glucocorticoid-dependent and -independent circuits

Proceedings of the National Academy of Sciences · 2020 · 25 citations

• Neuroscience
• Biology
• Psychology

There is extensive evidence that glucocorticoid hormones enhance memory consolidation, helping to ensure that emotionally significant events are well remembered. Prior findings suggest that the anteroventral region of bed nuclei of the stria terminalis (avBST) regulates glucocorticoid release, suggesting the potential for avBST activity to influence memory consolidation following an emotionally arousing learning event. To investigate this issue, male Sprague-Dawley rats underwent inhibitory avoidance training and repeated measurement of stress hormones, immediately followed by optogenetic manipulations of either the avBST or its projections to downstream regions, and 48 h later were tested for retention. The results indicate that avBST inhibition augmented posttraining pituitary-adrenal output and enhanced the memory for inhibitory avoidance training. Pretreatment with a glucocorticoid synthesis inhibitor blocked the memory enhancement as well as the potentiated corticosterone response, indicating the dependence of the memory enhancement on glucocorticoid release during the immediate posttraining period. In contrast, posttraining avBST stimulation decreased retention yet had no effect on stress hormonal output. Subsequent experiments revealed that inhibition of avBST input to the paraventricular hypothalamus enhanced stress hormonal output and subsequent retention, whereas stimulation did not affect either. Conversely, stimulation-but not inhibition-of avBST input to the ventrolateral periaqueductal gray impaired consolidation, whereas neither manipulation affected glucocorticoid secretion. These findings indicate that divergent pathways from the avBST are responsible for the mnemonic effects of avBST inhibition versus stimulation and do so via glucocorticoid-dependent and -independent mechanisms, respectively.

ISPNE Opening Plenary: Creating lasting memories – Involvement of stress hormones and amygdala activation

Psychoneuroendocrinology · 2019-02-01

Involvement of the Amygdala in the Regulation of Memory Storage

2019-01-22 · 46 citations

The central hypothesis is that emotionally arousing stimulation activates the amygdala and that activation results in modulation of the storage of acquired information. Although there is substantial evidence suggesting that memory storage, particularly storage of affective memory, may occur within the amygdala, other findings suggest that the amygdala influences memory storage occurring in other brain systems. Although studies of the effects of brain lesions have been important in efforts to understand the role of the amygdala in memory, interpretations of the findings of lesion studies are complicated by the fact that electrolytic, radio frequency, or neurotoxic lesions of the amygdala alter processes other than those directly involved in memory. Extensive evidence indicating that retention can be enhanced by posttraining administration of stimulant drugs suggests that memory storage may be modulated by the actions of endogenous neurotransmitters and hormones released by emotionally arousing stimulation.