The Modulation by the Locus Coeruleus of Recent and Remote Memory Retrieval is Activity‐Dependent DOI Creative Commons

Natalia Babushkina,

Denise Manahan‐Vaughan

Hippocampus, Journal Year: 2025, Volume and Issue: 35(2)

Published: Feb. 20, 2025

ABSTRACT The hippocampus plays a crucial role in acquiring, storing, and retrieving associative experience. Whereas neuromodulatory control of the by locus coeruleus (LC) enhances memory acquisition consolidation, less is known about its influence on retrieval. LC fires at tonic (0.5–8 Hz) phasic frequencies (10–25 Hz), relative to arousal affective states. Here, we explored what extent stimulation different (2–100 respective patterns, before retrieval recently acquired or remote spatial memory, alter working (WM) reference (RM) male rats. animals learned task an eight‐arm radial maze over period 15 days. recent testing did not affect WM. However, 20 100 Hz, but 5–10 impaired consolidated RM. These frequency‐dependent impairments were abolished intracerebral β‐adrenergic receptor (β‐AR), D1/D5 receptor, antagonism. When was assessed 4 weeks after initial consolidation (Day 34), RM significantly compared final day (on Day 6). altered 2–100 Hz improved Taken together, these data suggest that NA release from disrupts via activation β‐AR. Strikingly, increasing activity general improves WM remotely learning task, testing, suggesting increased effort sustaining past requires higher engagement.

Language: Английский

Memory engrams: Recalling the past and imagining the future DOI Open Access
Sheena A. Josselyn, Susumu Tonegawa

Science, Journal Year: 2020, Volume and Issue: 367(6473)

Published: Jan. 3, 2020

In 1904, Richard Semon introduced the term "engram" to describe neural substrate for storing memories. An experience, proposed, activates a subset of cells that undergo off-line, persistent chemical and/or physical changes become an engram. Subsequent reactivation this engram induces memory retrieval. Although Semon's contributions were largely ignored in his lifetime, new technologies allow researchers image and manipulate brain at level individual neurons has reinvigorated research. We review recent progress studying engrams, including evaluation evidence existence importance intrinsic excitability synaptic plasticity lifetime Together, these findings are beginning define as basic unit memory.

Language: Английский

Citations

838
Encouraging an excitable brain state: mechanisms of brain repair in stroke DOI
Mary T. Joy, S. Thomas Carmichael

Nature reviews. Neuroscience, Journal Year: 2020, Volume and Issue: 22(1), P. 38 - 53

Published: Nov. 12, 2020

Language: Английский

Citations

185
Adeno-Associated Viral Vectors in Neuroscience Research DOI Creative Commons
David L. Haggerty, Gregory G. Grecco, Kaitlin C. Reeves

et al.

Molecular Therapy — Methods & Clinical Development, Journal Year: 2019, Volume and Issue: 17, P. 69 - 82

Published: Nov. 26, 2019

Adeno-associated viral vectors (AAVs) are increasingly useful preclinical tools in neuroscience research studies for interrogating cellular and neurocircuit functions mapping brain connectivity. Clinically, AAVs showing increasing promise as viable candidates treating multiple neurological diseases. Here, we briefly review the utility of neurocircuits, manipulating neuronal function gene expression, activity labeling well AAV-based therapies diseases nervous system. This highlights vast potential that have transformative therapeutics neurosciences.

Language: Английский

Citations

100
A neural substrate of compulsive alcohol use DOI Creative Commons
Esi Domi, Li Xu, Sanne Toivainen

et al.

Science Advances, Journal Year: 2021, Volume and Issue: 7(34)

Published: Aug. 18, 2021

Alcohol intake remains controlled in a majority of users but becomes "compulsive," i.e., continues despite adverse consequences, minority who develop alcohol addiction. Here, using footshock-punished self-administration procedure, we screened large population outbred rats to identify those showing compulsivity operationalized as punishment-resistant self-administration. Using unsupervised clustering, found that this behavior emerged stable trait subpopulation and was associated with activity brain network included central nucleus the amygdala (CeA). Activity PKCδ

Language: Английский

Citations

72
Glucocorticoids Promote Fear Generalization by Increasing the Size of a Dentate Gyrus Engram Cell Population DOI Creative Commons
Sylvie L. Lesuis, Niek Brosens,

Nathalie Immerzeel

et al.

Biological Psychiatry, Journal Year: 2021, Volume and Issue: 90(7), P. 494 - 504

Published: April 24, 2021

BackgroundTraumatic experiences, such as conditioned threat, are coded enduring memories that frequently subject to generalization, which is characterized by (re-) expression of fear in safe environments. However, the neurobiological mechanisms underlying threat generalization after a traumatic experience and role stress hormones this process remain poorly understood.MethodsWe examined influence glucocorticoid on strength specificity memory at level sparsely distributed dentate gyrus (DG) engram cells male mice.ResultsWe found elevating conditioning induces generalized contextual response. This was accompanied selective persistent increase excitability number activated DG granule cells. Selective chemogenetic suppression these sparse prevented glucocorticoid-induced restored specificity, while leaving auditory unaffected.ConclusionsThese results implicate ensemble critical cellular substrate induced hormones.

Language: Английский

Citations

60
Neocortical synaptic engrams for remote contextual memories DOI Creative Commons
Jihye Lee, Woong Bin Kim, Eui-Ho Park

et al.

Nature Neuroscience, Journal Year: 2022, Volume and Issue: 26(2), P. 259 - 273

Published: Dec. 23, 2022

While initial encoding of contextual memories involves the strengthening hippocampal circuits, these progressively mature to stabilized forms in neocortex and become less hippocampus dependent. Although it has been proposed that long-term storage may involve enduring synaptic changes neocortical substrates remote have elusive. Here we demonstrate consolidation fear mice correlated with progressive excitatory connections between prefrontal cortical (PFC) engram neurons active during learning reactivated memory recall, whereas extinction weakened those synapses. This synapse-specific plasticity was CREB-dependent required sustained signals, which retrosplenial cortex could convey PFC. Moreover, PFC were strongly connected other recruited recall. Our study suggests circuits can contribute memories.

Language: Английский

Citations

58
Retraction of Astrocyte Leaflets From the Synapse Enhances Fear Memory DOI
Aina Badia‐Soteras, Tim S. Heistek, Mandy S. J. Kater

et al.

Biological Psychiatry, Journal Year: 2022, Volume and Issue: 94(3), P. 226 - 238

Published: Oct. 29, 2022

Language: Английский

Citations

49
Reactivation of Early-Life Stress-Sensitive Neuronal Ensembles Contributes to Lifelong Stress Hypersensitivity DOI Creative Commons
Julie‐Anne Balouek, Christabel Mclain, Adelaide R. Minerva

et al.

Journal of Neuroscience, Journal Year: 2023, Volume and Issue: 43(34), P. 5996 - 6009

Published: July 10, 2023

Early-life stress (ELS) is one of the strongest lifetime risk factors for depression, anxiety, suicide, and other psychiatric disorders, particularly after facing additional stressful events later in life. Human animal studies demonstrate that ELS sensitizes individuals to subsequent stress. However, neurobiological basis such sensitization remains largely unexplored. We hypothesized ELS-induced would be detectable at level neuronal ensembles, cells activated by more reactive adult To test this, we leveraged transgenic mice genetically tag, track, manipulate experience-activated neurons. found both male female mice, ELS-activated neurons within nucleus accumbens (NAc), a lesser extent medial prefrontal cortex, were preferentially reactivated whether reactivation ensembles NAc contributes hypersensitivity, expressed hM4Dis receptor control or pups chemogenetically inhibited their activity during experience Inhibition neurons, but not control-tagged ameliorated social avoidance behavior following chronic defeat males. These data provide evidence hypersensitivity encoded corticolimbic ensembles. SIGNIFICANCE STATEMENT enhances sensitivity life, yet mechanisms are unknown. Here, show brain regions remain hypersensitive across life span, quieting these rescues hypersensitivity.

Language: Английский

Citations

24
Memory circuits in dementia: The engram, hippocampal neurogenesis and Alzheimer’s disease DOI Creative Commons
Orly Lazarov, Muskan Gupta, Pavan Kumar

et al.

Progress in Neurobiology, Journal Year: 2024, Volume and Issue: 236, P. 102601 - 102601

Published: April 1, 2024

Here, we provide an in-depth consideration of our current understanding engrams, spanning from molecular to network levels, and hippocampal neurogenesis, in health Alzheimer's disease (AD). This review highlights novel findings these emerging research fields future directions for therapeutic avenues memory failure dementia. Engrams, AD, neurogenesis have each been extensively studied. The integration topics, however, has relatively less deliberated, is the focus this review. We primarily on dentate gyrus (DG) hippocampus, which a key area episodic formation. Episodic significantly impaired also site adult neurogenesis. Advancements technology, especially opto- chemogenetics, made sophisticated manipulations engram cells possible. Furthermore, innovative methods emerged monitoring neurons, even specific neuronal populations, vivo while animals engage tasks, such as calcium imaging. In imaging contributes more comprehensive cells. Critically, studies DG using technologies shown important contribution both AD. Together, discussion topics provides holistic perspective that motivates questions research.

Language: Английский

Citations

12
Hippocampal DNA methylation promotes contextual fear memory persistence by facilitating systems consolidation and cortical engram stabilization. DOI
Janina Kupke,

Stefanos Loizou,

C. Peter Bengtson

et al.

Biological Psychiatry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

1