Partial or complete loss of norepinephrine differentially alters contextual fear and catecholamine release dynamics in hippocampal CA1 DOI Open Access
Leslie R. Wilson,

Nicholas W. Plummer,

Irina Y. Evsyukova

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: March 27, 2023

ABSTRACT Contextual fear learning is heavily dependent on the hippocampus. Despite evidence that catecholamines contribute to contextual encoding and memory retrieval, precise temporal dynamics of their release in hippocampus during behavior unknown. In addition, new animal models are required probe effects altered catecholamine synthesis learning. Utilizing GRAB NE DA sensors, vivo fiber photometry, two mouse locus coeruleus norepinephrine (LC-NE) synthesis, we investigate (NE) dopamine (DA) dorsal hippocampal CA1 conditioning. We report aversive foot-shock increases both CA1, while freezing associated with recall accompanied by decreased release. Partial loss LC-NE reveals modulated sex. Moreover, find recent sensitive partial complete throughout prenatal postnatal development, similar prior observations mice global beginning postnatally. contrast, remote compromised only prenatally. Overall, these findings provide novel insights into role behavior, highlight a complex relationship between genotype, sex, signaling.

Language: Английский

Dopaminergic regulation of hippocampal plasticity, learning, and memory DOI Creative Commons
Theodoros Tsetsenis, John I. Broussard, John A. Dani

et al.

Frontiers in Behavioral Neuroscience, Journal Year: 2023, Volume and Issue: 16

Published: Jan. 27, 2023

The hippocampus is responsible for encoding behavioral episodes into short-term and long-term memory. circuits that mediate these processes are subject to neuromodulation, which involves regulation of synaptic plasticity local neuronal excitability. In this review, we present evidence demonstrate the influence dopaminergic neuromodulation on hippocampus-dependent memory, address controversy surrounding source dopamine innervation. First, summarize historical recent retrograde anterograde anatomical tracing studies direct projections from ventral tegmental area discuss release adrenergic locus coeruleus . Then, modulation in hippocampus. Plasticity mechanisms examined brain slices recordings vivo populations freely moving rodents. Finally, review pharmacological, genetic, circuitry research demonstrates importance learning memory tasks while dissociating anatomically distinct inputs.

Language: Английский

Citations

30
Frontal Norepinephrine Represents a Threat Prediction Error Under Uncertainty DOI
Aakash Basu,

Jen-Hau Yang,

Abigail L. Yu

et al.

Biological Psychiatry, Journal Year: 2024, Volume and Issue: 96(4), P. 256 - 267

Published: Feb. 4, 2024

Language: Английский

Citations

10
Interplay of hippocampal long-term potentiation and long-term depression in enabling memory representations DOI Creative Commons
Hardy Hagena, Denise Manahan‐Vaughan

Philosophical Transactions of the Royal Society B Biological Sciences, Journal Year: 2024, Volume and Issue: 379(1906)

Published: June 10, 2024

Hippocampal long-term potentiation (LTP) and depression (LTD) are Hebbian forms of synaptic plasticity that widely believed to comprise the physiological correlates associative learning. They a persistent, input-specific increase or decrease, respectively, in efficacy that, rodents, can be followed for days weeks vivo . Persistent (>24 h) LTP LTD exhibit distinct frequency-dependencies molecular profiles hippocampal subfields. Moreover, causal genetic studies behaving rodents indicate both fulfil specific complementary roles acquisition retention spatial memory. is likely responsible generation record experience, which may serve as an schema re-used expedite facilitate subsequent In contrast, enable modification dynamic updating this representation, such detailed content information included rendered unique distinguishable from other similar representations. Together, engage interplay supports complex memories resistant generalization. This article part discussion meeting issue ‘Long-term potentiation: 50 years on’.

Language: Английский

Citations

9
The impact of chronic intermittent hypoxia on enzymatic activity in memory-associated brain regions of male and female rats DOI Creative Commons
Steve Mabry, Jessica L. Bradshaw,

Jennifer J. Gardner

et al.

Biology of Sex Differences, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 31, 2025

Obstructive sleep apnea (OSA) is an intermittent hypoxia disorder associated with cognitive dysfunction, including learning and memory impairments. There evidence that alterations in protease activity neuronal activation are dependent on sex, may be brain region-specific. However, the mechanisms mediating OSA-induced impairments unclear. Therefore, we used a rat model of OSA, chronic (CIH) to investigate (e.g., calpain caspase-3) spectrin, cytoskeletal protein neurotransmitter release, (early growth response 1, EGR-1) regions memory. Male female Sprague Dawley rats were exposed CIH or room air (normoxic) for 14 days. We quantified cleaved spectrin products, along EGR-1 expression hippocampal subregions (CA1, CA3), cortical [entorhinal cortex (ETC), retrosplenial (RSC), cerebellar (CC)], subcortical [raphe nucleus (RN), locus coeruleus (LC)] Within each group, Pearson correlations activity, caspase-3 performed between regions. Sex differences within normoxic examined. dysregulated male ETC, CA1 RSC. RN, decreased cleavage products ETC. calpain-cleaved RSC but increased these was RN. Correlational analysis revealed excitatory connections males inhibitory females. shifted from negative positive correlations. Overall, data indicate dysregulates impairs function region- sex-dependent manner. This indicates females exhibit sex-specific vulnerabilities mild OSA. These findings concur our previous behavioral studies demonstrated impairment CIH-exposed rats.

Language: Английский

Citations

1
Chronic Pain–Related Cognitive Deficits: Preclinical Insights into Molecular, Cellular, and Circuit Mechanisms DOI
Siyi Han, Jie Wang, Wen Zhang

et al.

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 61(10), P. 8123 - 8143

Published: March 12, 2024

Language: Английский

Citations

8
Norepinephrine release in the cerebellum contributes to aversive learning DOI Creative Commons
Adrien Stanley, Michael R. Post,

Clay Lacefield

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Aug. 10, 2023

Abstract The modulation of dopamine release from midbrain projections to the striatum has long been demonstrated in reward-based learning, but synaptic basis aversive learning is far less characterized. cerebellum receives axonal locus coeruleus, and norepinephrine implicated states arousal stress, whether relies on plastic changes unknown. Here we report that mice, released following an unpredicted noxious event (a foot-shock) this potentiated powerfully with fear acquisition as animals learn a previously neutral stimulus (tone) predicts event. Importantly, both chemogenetic optogenetic inhibition coeruleus-cerebellum pathway block memory without impairing motor function. Thus, modulated by experience underlies learning.

Language: Английский

Citations

16
The β‐adrenergic hypothesis of synaptic and microglial impairment in Alzheimer's disease DOI Open Access
Shaomin Li

Journal of Neurochemistry, Journal Year: 2023, Volume and Issue: 165(3), P. 289 - 302

Published: Feb. 17, 2023

Alzheimer's disease (AD) is a progressive neurodegenerative originating partly from amyloid β protein-induced synaptic failure. As damaging of noradrenergic neurons in the locus coeruleus (LC) occurs at prodromal stage AD, activation adrenergic receptors could serve as first line defense against onset disease. Activation β2 -ARs strengthens long-term potentiation (LTP) and activity, thus improving learning memory. Physical stimulation animals exposed to an enriched environment (EE) leads prevents dysfunction. EE also suppresses neuroinflammation, suggesting that -AR agonists may play neuroprotective role. The used for respiratory diseases have been shown anti-inflammatory effect. Epidemiological studies further support beneficial effects on several diseases. Thus, I propose provide therapeutic value combination with novel treatments AD.

Language: Английский

Citations

12
Photostimulation of Locus Coeruleus CA1 catecholaminergic terminals reversed spatial memory impairment in an Alzheimer's disease mouse model. DOI
Donovan K. Gálvez-Márquez, Oscar Urrego-Morales,

Luis F. Rodríguez-Durán

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 22, 2025

Abstract Rationale One of the earliest changes associated with Alzheimer's disease (AD) is loss catecholaminergic terminals in cortex and hippocampus originating from Locus Coeruleus (LC). This decline leads to reduced neurotransmitters hippocampus, affecting synaptic plasticity spatial memory. However, it unclear whether restoring transmission LC may alleviate memory deficits AD. Objectives study investigates how optogenetic stimulation projections locus coeruleus hippocampal CA1 region enhance disease. Methods We conducted experiments using a 12-month-old 3xTg-AD mouse model (AD-TH), which expresses Cre recombinase under control tyrosine hydroxylase (TH) gene. allowed us photostimulate before performing two different tasks inducing long-term potentiation (LTP). Results Optogenetic successfully reversed impairment retrieval aging AD-TH mice. Furthermore, this restored neurotransmitter levels enhanced plasticity, as demonstrated by an LTP protocol. Conclusions These findings indicate that circuitry (LC) plays crucial role disrupting contributing seen early stages highlights potential therapeutic benefits targeting neurons improve cognitive function patients

Language: Английский

Citations

0
Event boundaries drive norepinephrine release and distinctive neural representations of space in the rodent hippocampus DOI Open Access
Sam McKenzie,

Alexandra L. Sommer,

Tia N. Donaldson

et al.

Published: Jan. 31, 2025

Episodic memories are temporally segmented around event boundaries that tend to coincide with moments of environmental change. During these times, the state brain should change rapidly, or reset, ensure information encountered before and after an boundary is encoded in different neuronal populations. Norepinephrine (NE) thought facilitate this network reorganization. However, it unknown whether drive NE release hippocampus and, if so, how relates changes hippocampal firing patterns. The advent new GRAB sensor now allows for measurement binding sub-second resolution. Using tool mice, we tested released into dorsal during defined by unexpected transitions between spatial contexts presentations novel objections. We found dynamics were well explained time elapsed each changes, not related conditioned behaviors, exploratory bouts movement, reward. Familiarity a context accelerated rate which phasic decayed baseline. Knowing when elevated, coding space differs moments. Immediately observed relatively unique patterns neural spiking settled modal at similar returned These results consistent model wherein drives representations away from steady-state attractor. hypothesize distinctive codes may long-term memory contribute basis primacy effect.

Language: Английский

Citations

0
Event boundaries drive norepinephrine release and distinctive neural representations of space in the rodent hippocampus DOI Open Access
Sam McKenzie,

Alexandra L. Sommer,

Tia N. Donaldson

et al.

Published: Jan. 31, 2025

Episodic memories are temporally segmented around event boundaries that tend to coincide with moments of environmental change. During these times, the state brain should change rapidly, or reset, ensure information encountered before and after an boundary is encoded in different neuronal populations. Norepinephrine (NE) thought facilitate this network reorganization. However, it unknown whether drive NE release hippocampus and, if so, how relates changes hippocampal firing patterns. The advent new GRAB sensor now allows for measurement binding sub-second resolution. Using tool mice, we tested released into dorsal during defined by unexpected transitions between spatial contexts presentations novel objections. We found dynamics were well explained time elapsed each changes, not related conditioned behaviors, exploratory bouts movement, reward. Familiarity a context accelerated rate which phasic decayed baseline. Knowing when elevated, coding space differs moments. Immediately observed relatively unique patterns neural spiking settled modal at similar returned These results consistent model wherein drives representations away from steady-state attractor. hypothesize distinctive codes may long-term memory contribute basis primacy effect.

Language: Английский

Citations

0