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Article ; Online: Glucocorticoid effects on working memory impairment require l-type calcium channel activity within prefrontal cortex.

Barsegyan, Areg / McGaugh, James L / Roozendaal, Benno

2022 Volume 197, Page(s) 107700

Abstract: 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). ... ...

Abstract	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 Ca
MeSH term(s)	Rats ; Animals ; Male ; Memory, Short-Term/physiology ; Glucocorticoids/pharmacology ; Calcium Channels, L-Type/metabolism ; Rats, Sprague-Dawley ; Diltiazem/metabolism ; Diltiazem/pharmacology ; Memory Disorders ; Prefrontal Cortex/physiology
Chemical Substances	Glucocorticoids ; adenosine-3',5'-cyclic phosphorothioate (23645-17-2) ; Calcium Channels, L-Type ; Diltiazem (EE92BBP03H)
Language	English
Publishing date	2022-11-18
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1223366-3
ISSN	1095-9564 ; 1074-7427
ISSN (online)	1095-9564
ISSN	1074-7427
DOI	10.1016/j.nlm.2022.107700
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Article ; Online: Basolateral amygdala noradrenergic activity is required for enhancement of object recognition memory by histone deacetylase inhibition in the anterior insular cortex.

Chen, Yanfen / Barsegyan, Areg / Nadif Kasri, Nael / Roozendaal, Benno

Neuropharmacology

2018 Volume 141, Page(s) 32–41

Abstract: Extensive evidence indicates that noradrenergic activation of the basolateral amygdala (BLA) is essential for mediating emotional arousal effects on memory consolidation in different target regions. However, the mechanism by which BLA activation ... ...

Abstract	Extensive evidence indicates that noradrenergic activation of the basolateral amygdala (BLA) is essential for mediating emotional arousal effects on memory consolidation in different target regions. However, the mechanism by which BLA activation regulates such information storage processes remains largely elusive. Here we demonstrate, in male Sprague-Dawley rats, that noradrenergic activation of the BLA is critically involved in enabling facilitation of memory consolidation induced by histone acetylation, a form of chromatin modification, within the insular cortex (IC) on object recognition memory. The histone deacetylase (HDAC) inhibitor sodium butyrate (NaB) administered either systemically or directly into the anterior, but not posterior, IC immediately after object recognition training enhanced long-term memory for the identity of the object. Systemic NaB administration also enhanced memory for the location of the object. This NaB-induced enhancement of both object recognition and object location memory was selectively associated with an increased ability to assess the familiarity of the training stimulus, without affecting interaction with a novel stimulus. The β-adrenoceptor antagonist propranolol infused into the BLA concurrently abolished the NaB-induced enhancement of familiarity detection underlying both object recognition and object location memory. These findings indicate that noradrenergic activity within the BLA induced by emotional arousal interacts with chromatin modification mechanisms in its target regions to affect post-learning consolidation processes underlying long-term recognition memory and discrimination of a familiar stimulus.
MeSH term(s)	Adrenergic Neurons/physiology ; Animals ; Basolateral Nuclear Complex/drug effects ; Butyric Acid/administration & dosage ; Butyric Acid/antagonists & inhibitors ; Butyric Acid/pharmacology ; Cerebral Cortex/drug effects ; Histone Deacetylase Inhibitors/pharmacology ; Male ; Memory, Long-Term/drug effects ; Microinjections ; Propranolol/pharmacology ; Rats ; Recognition (Psychology)/drug effects ; Recognition (Psychology)/physiology ; Spatial Memory/drug effects
Chemical Substances	Histone Deacetylase Inhibitors ; Butyric Acid (107-92-6) ; Propranolol (9Y8NXQ24VQ)
Language	English
Publishing date	2018-08-18
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218272-5
ISSN	1873-7064 ; 0028-3908
ISSN (online)	1873-7064
ISSN	0028-3908
DOI	10.1016/j.neuropharm.2018.08.018
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Article: Noradrenergic activation of the basolateral amygdala enhances object recognition memory and induces chromatin remodeling in the insular cortex.

Beldjoud, Hassiba / Barsegyan, Areg / Roozendaal, Benno

Frontiers in behavioral neuroscience

2015 Volume 9, Page(s) 108

Abstract: It is well established that arousal-induced memory enhancement requires noradrenergic activation of the basolateral complex of the amygdala (BLA) and modulatory influences on information storage processes in its many target regions. While this concept is ...

Abstract	It is well established that arousal-induced memory enhancement requires noradrenergic activation of the basolateral complex of the amygdala (BLA) and modulatory influences on information storage processes in its many target regions. While this concept is well accepted, the molecular basis of such BLA effects on neural plasticity changes within other brain regions remains to be elucidated. The present study investigated whether noradrenergic activation of the BLA after object recognition training induces chromatin remodeling through histone post-translational modifications in the insular cortex (IC), a brain region that is importantly involved in object recognition memory. Male Sprague-Dawley rats were trained on an object recognition task, followed immediately by bilateral microinfusions of norepinephrine (1.0 μg) or saline administered into the BLA. Saline-treated control rats exhibited poor 24-h retention, whereas norepinephrine treatment induced robust 24-h object recognition memory. Most importantly, this memory-enhancing dose of norepinephrine induced a global reduction in the acetylation levels of histone H3 at lysine 14, H2B and H4 in the IC 1 h later, whereas it had no effect on the phosphorylation of histone H3 at serine 10 or tri-methylation of histone H3 at lysine 27. Norepinephrine administered into the BLA of non-trained control rats did not induce any changes in the histone marks investigated in this study. These findings indicate that noradrenergic activation of the BLA induces training-specific effects on chromatin remodeling mechanisms, and presumably gene transcription, in its target regions, which may contribute to the understanding of the molecular mechanisms of stress and emotional arousal effects on memory consolidation.
Language	English
Publishing date	2015-04-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2452960-6
ISSN	1662-5153
ISSN	1662-5153
DOI	10.3389/fnbeh.2015.00108
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Article: Noradrenergic activation of the basolateral amygdala modulates the consolidation of object-in-context recognition memory.

Barsegyan, Areg / McGaugh, James L / Roozendaal, Benno

Frontiers in behavioral neuroscience

2014 Volume 8, Page(s) 160

Abstract: Noradrenergic activation of the basolateral complex of the amygdala (BLA) is well known to enhance the consolidation of long-term memory of highly emotionally arousing training experiences. The present study investigated whether such noradrenergic ... ...

Abstract	Noradrenergic activation of the basolateral complex of the amygdala (BLA) is well known to enhance the consolidation of long-term memory of highly emotionally arousing training experiences. The present study investigated whether such noradrenergic activation of the BLA also influences the consolidation of object-in-context recognition memory, a low-arousing training task assessing episodic-like memory. Male Sprague-Dawley rats were exposed to two identical objects in one context for either 3 or 10 min, immediately followed by exposure to two other identical objects in a distinctly different context. Immediately after the training they received bilateral intra-BLA infusions of norepinephrine (0.3, 1.0, or 3.0 μ g) or the β-adrenoceptor antagonist propranolol (0.1, 0.3, or 1.0 μ g). On the 24-h retention test, rats were placed back into one of the training contexts with one copy of each of the two training objects. Thus, although both objects were familiar, one of the objects had not previously been encountered in this particular test context. Hence, if the animal generated a long-term memory for the association between an object and its context, it would spend significantly more time exploring the object that was not previously experienced in this context. Saline-infused control rats exhibited poor 24-h retention when given 3 min of training and good retention when given 10 min of training. Norepinephrine administered after 3 min of object-in-context training induced a dose-dependent memory enhancement, whereas propranolol administered after 10 min of training produced memory impairment. These findings provide evidence that post-training noradrenergic activation of the BLA also enhances the consolidation of memory of object-in-context recognition training, enabling accuracy of episodic-like memories.
Language	English
Publishing date	2014-05-08
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2452960-6
ISSN	1662-5153
ISSN	1662-5153
DOI	10.3389/fnbeh.2014.00160
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Article ; Online: Mouse visual cortex contains a region of enhanced spatial resolution.

van Beest, Enny H / Mukherjee, Sreedeep / Kirchberger, Lisa / Schnabel, Ulf H / van der Togt, Chris / Teeuwen, Rob R M / Barsegyan, Areg / Meyer, Arne F / Poort, Jasper / Roelfsema, Pieter R / Self, Matthew W

Nature communications

2021 Volume 12, Issue 1, Page(s) 4029

Abstract: The representation of space in mouse visual cortex was thought to be relatively uniform. Here we reveal, using population receptive-field (pRF) mapping techniques, that mouse visual cortex contains a region in which pRFs are considerably smaller. This ... ...

Abstract	The representation of space in mouse visual cortex was thought to be relatively uniform. Here we reveal, using population receptive-field (pRF) mapping techniques, that mouse visual cortex contains a region in which pRFs are considerably smaller. This region, the "focea," represents a location in space in front of, and slightly above, the mouse. Using two-photon imaging we show that the smaller pRFs are due to lower scatter of receptive-fields at the focea and an over-representation of binocular regions of space. We show that receptive-fields of single-neurons in areas LM and AL are smaller at the focea and that mice have improved visual resolution in this region of space. Furthermore, freely moving mice make compensatory eye-movements to hold this region in front of them. Our results indicate that mice have spatial biases in their visual processing, a finding that has important implications for the use of the mouse model of vision.
MeSH term(s)	Animals ; Eye Movements/physiology ; Female ; Head Movements/physiology ; Male ; Mice ; Mice, Inbred C57BL ; Photic Stimulation ; Visual Cortex/physiology ; Visual Fields/physiology ; Visual Perception/physiology
Language	English
Publishing date	2021-06-29
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-021-24311-5
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Article ; Online: The essential role of recurrent processing for figure-ground perception in mice.

Kirchberger, Lisa / Mukherjee, Sreedeep / Schnabel, Ulf H / van Beest, Enny H / Barsegyan, Areg / Levelt, Christiaan N / Heimel, J Alexander / Lorteije, Jeannette A M / van der Togt, Chris / Self, Matthew W / Roelfsema, Pieter R

Science advances

2021 Volume 7, Issue 27

Abstract: The segregation of figures from the background is an important step in visual perception. In primary visual cortex, figures evoke stronger activity than backgrounds during a delayed phase of the neuronal responses, but it is unknown how this figure- ... ...

Abstract	The segregation of figures from the background is an important step in visual perception. In primary visual cortex, figures evoke stronger activity than backgrounds during a delayed phase of the neuronal responses, but it is unknown how this figure-ground modulation (FGM) arises and whether it is necessary for perception. Here, we show, using optogenetic silencing in mice, that the delayed V1 response phase is necessary for figure-ground segregation. Neurons in higher visual areas also exhibit FGM and optogenetic silencing of higher areas reduced FGM in V1. In V1, figures elicited higher activity of vasoactive intestinal peptide-expressing (VIP) interneurons than the background, whereas figures suppressed somatostatin-positive interneurons, resulting in an increased activation of pyramidal cells. Optogenetic silencing of VIP neurons reduced FGM in V1, indicating that disinhibitory circuits contribute to FGM. Our results provide insight into how lower and higher areas of the visual cortex interact to shape visual perception.
Language	English
Publishing date	2021-06-30
Publishing country	United States
Document type	Journal Article
ZDB-ID	2810933-8
ISSN	2375-2548 ; 2375-2548
ISSN (online)	2375-2548
ISSN	2375-2548
DOI	10.1126/sciadv.abe1833
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Article ; Online: Glucocorticoid enhancement of recognition memory via basolateral amygdala-driven facilitation of prelimbic cortex interactions.

Barsegyan, Areg / Mirone, Gabriele / Ronzoni, Giacomo / Guo, Chunan / Song, Qi / van Kuppeveld, Daan / Schut, Evelien H S / Atsak, Piray / Teurlings, Selina / McGaugh, James L / Schubert, Dirk / Roozendaal, Benno

Proceedings of the National Academy of Sciences of the United States of America

2019 Volume 116, Issue 14, Page(s) 7077–7082

Abstract: Extensive evidence indicates that the basolateral amygdala (BLA) interacts with other brain regions in mediating stress hormone and emotional arousal effects on memory consolidation. Brain activation studies have shown that arousing conditions lead to ... ...

Abstract	Extensive evidence indicates that the basolateral amygdala (BLA) interacts with other brain regions in mediating stress hormone and emotional arousal effects on memory consolidation. Brain activation studies have shown that arousing conditions lead to the activation of large-scale neural networks and several functional connections between brain regions beyond the BLA. Whether such distal interactions on memory consolidation also depend on BLA activity is not as yet known. We investigated, in male Sprague-Dawley rats, whether BLA activity enables prelimbic cortex (PrL) interactions with the anterior insular cortex (aIC) and dorsal hippocampus (dHPC) in regulating glucocorticoid effects on different components of object recognition memory. The glucocorticoid receptor (GR) agonist RU 28362 administered into the PrL, but not infralimbic cortex, immediately after object recognition training enhanced 24-hour memory of both the identity and location of the object via functional interactions with the aIC and dHPC, respectively. Importantly, posttraining inactivation of the BLA by the noradrenergic antagonist propranolol abolished the effect of GR agonist administration into the PrL on memory enhancement of both the identity and location of the object. BLA inactivation by propranolol also blocked the effect of GR agonist administration into the PrL on inducing changes in neuronal activity within the aIC and dHPC during the postlearning consolidation period as well as on structural changes in spine morphology assessed 24 hours later. These findings provide evidence that BLA noradrenergic activity enables functional interactions between the PrL and the aIC and dHPC in regulating stress hormone and emotional arousal effects on memory.
MeSH term(s)	Androstanols/pharmacology ; Animals ; Basolateral Nuclear Complex/metabolism ; Cerebral Cortex/metabolism ; Glucocorticoids/metabolism ; Male ; Memory/drug effects ; Nerve Net/metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Glucocorticoid/agonists ; Receptors, Glucocorticoid/metabolism
Chemical Substances	Androstanols ; Glucocorticoids ; Receptors, Glucocorticoid ; 11,17-dihydroxy-6-methyl-17-(1-propynyl)androsta-1,4,6-triene-3-one (74915-64-3)
Language	English
Publishing date	2019-03-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.1901513116
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Article: Adrenal stress hormones, amygdala activation, and memory for emotionally arousing experiences.

Roozendaal, Benno / Barsegyan, Areg / Lee, Sangkwan

Progress in brain research

2008 Volume 167, Page(s) 79–97

Abstract: Extensive evidence indicates that stress hormones released from the adrenal glands are critically involved in memory consolidation of emotionally arousing experiences. Epinephrine or glucocorticoids administered after exposure to emotionally arousing ... ...

Abstract	Extensive evidence indicates that stress hormones released from the adrenal glands are critically involved in memory consolidation of emotionally arousing experiences. Epinephrine or glucocorticoids administered after exposure to emotionally arousing experiences enhance the consolidation of long-term memories of these experiences. Our findings indicate that adrenal stress hormones influence memory consolidation via interactions with arousal-induced activation of noradrenergic mechanisms within the amygdala. In turn, the amygdala regulates memory consolidation via its efferent projections to many other brain regions. In contrast to the enhancing effects on consolidation, high circulating levels of stress hormones impair memory retrieval and working memory. Such effects also require noradrenergic activation of the amygdala and interactions with other brain regions.
MeSH term(s)	Adrenal Cortex Hormones/physiology ; Amygdala/physiopathology ; Animals ; Arousal/physiology ; Brain/physiology ; Brain/physiopathology ; Emotions/physiology ; Humans ; Memory/physiology ; Memory, Short-Term/physiology ; Mental Recall/physiology ; Stress, Physiological/physiopathology
Chemical Substances	Adrenal Cortex Hormones
Language	English
Publishing date	2008
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ISSN	0079-6123
ISSN	0079-6123
DOI	10.1016/S0079-6123(07)67006-X
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Article ; Online: The Vasopressin 1b Receptor Antagonist A-988315 Blocks Stress Effects on the Retrieval of Object-Recognition Memory.

Barsegyan, Areg / Atsak, Piray / Hornberger, Wilfried B / Jacobson, Peer B / van Gaalen, Marcel M / Roozendaal, Benno

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

2015 Volume 40, Issue 8, Page(s) 1979–1989

Abstract: Stress-induced activation of the hypothalamo-pituitary-adrenocortical (HPA) axis and high circulating glucocorticoid levels are well known to impair the retrieval of memory. Vasopressin can activate the HPA axis by stimulating vasopressin 1b (V1b) ... ...

Abstract	Stress-induced activation of the hypothalamo-pituitary-adrenocortical (HPA) axis and high circulating glucocorticoid levels are well known to impair the retrieval of memory. Vasopressin can activate the HPA axis by stimulating vasopressin 1b (V1b) receptors located on the pituitary. In the present study, we investigated the effect of A-988315, a selective and highly potent non-peptidergic V1b-receptor antagonist with good pharmacokinetic properties, in blocking stress effects on HPA-axis activity and memory retrieval. To study cognitive performance, male Sprague-Dawley rats were trained on an object-discrimination task during which they could freely explore two identical objects. Memory for the objects and their location was tested 24 h later. A-988315 (20 or 60 mg/kg) or water was administered orally 90 min before retention testing, followed 60 min later by stress of footshock exposure. A-988315 dose-dependently dampened stress-induced increases in corticosterone plasma levels, but did not significantly alter HPA-axis activity of non-stressed control rats. Most importantly, A-988315 administration prevented stress-induced impairment of memory retrieval on both the object-recognition and the object-location tasks. A-988315 did not alter the retention of non-stressed rats and did not influence the total time spent exploring the objects or experimental context in either stressed or non-stressed rats. Thus, these findings indicate that direct antagonism of V1b receptors is an effective treatment to block stress-induced activation of the HPA axis and the consequent impairment of retrieval of different aspects of recognition memory.
MeSH term(s)	Adrenocorticotropic Hormone/blood ; Animals ; Antidiuretic Hormone Receptor Antagonists/therapeutic use ; Arginine Vasopressin/pharmacokinetics ; Corticosterone/blood ; Disease Models, Animal ; Exploratory Behavior/drug effects ; Humans ; Male ; Memory Disorders/drug therapy ; Memory Disorders/etiology ; Mental Recall/drug effects ; Piperazines/pharmacology ; Protein Binding/drug effects ; Rats ; Rats, Sprague-Dawley ; Receptors, Oxytocin/metabolism ; Receptors, Vasopressin/metabolism ; Recognition (Psychology)/drug effects ; Stress, Psychological/complications ; Sulfonamides/pharmacology ; Time Factors ; Tritium/pharmacokinetics
Chemical Substances	A-988315 ; Antidiuretic Hormone Receptor Antagonists ; Piperazines ; Receptors, Oxytocin ; Receptors, Vasopressin ; Sulfonamides ; Tritium (10028-17-8) ; Arginine Vasopressin (113-79-1) ; Adrenocorticotropic Hormone (9002-60-2) ; Corticosterone (W980KJ009P)
Language	English
Publishing date	2015-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	639471-1
ISSN	1740-634X ; 0893-133X
ISSN (online)	1740-634X
ISSN	0893-133X
DOI	10.1038/npp.2015.48
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Article: Glucocorticoids in the prefrontal cortex enhance memory consolidation and impair working memory by a common neural mechanism

Barsegyan, Areg / Mackenzie, Scott M / Kurose, Brian D / McGaugh, James L / Roozendaal, Benno

Proceedings of the National Academy of Sciences of the United States of America. 2010 Sept. 21, v. 107, no. 38

2010

Abstract: It is well established that acute administration of adrenocortical hormones enhances the consolidation of memories of emotional experiences and, concurrently, impairs working memory. These different glucocorticoid effects on these two memory functions ... ...

Abstract	It is well established that acute administration of adrenocortical hormones enhances the consolidation of memories of emotional experiences and, concurrently, impairs working memory. These different glucocorticoid effects on these two memory functions have generally been considered to be independently regulated processes. Here we report that a glucocorticoid receptor agonist administered into the medial prefrontal cortex (mPFC) of male Sprague-Dawley rats both enhances memory consolidation and impairs working memory. Both memory effects are mediated by activation of a membrane-bound steroid receptor and depend on noradrenergic activity within the mPFC to increase levels of cAMP-dependent protein kinase. These findings provide direct evidence that glucocorticoid effects on both memory consolidation and working memory share a common neural influence within the mPFC.
Keywords	agonists ; cAMP-dependent protein kinase ; cortex ; glucocorticoid receptors ; glucocorticoids ; males ; memory ; rats
Language	English
Dates of publication	2010-0921
Size	p. 16655-16660.
Publishing place	National Academy of Sciences
Document type	Article
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.1011975107
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