CaMKII Requirement for in Vivo Insular Cortex LTP Maintenance and CTA Memory Persistence

Juárez-Muñoz, Yectivani; Ramos-Languren, Laura E.; Escobar, Martha L.

doi:10.3389/fphar.2017.00822

Cited by 8 publications

(9 citation statements)

References 59 publications

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“…Inhibition of aIC-to-BLA neurons using local CNO delivery at the aIC further confirmed the necessity of the projection for CTA memory acquisition and expression ( Fig. 5E-I ), while suggesting that its recruitment acts upstream of BLA collaterals to reward centers (Dunn and Everitt, 1988;Juárez-Muñoz et al, 2017;Inui et al, 2019). Nonetheless, it is possible that aIC collaterals of the projection to other regions might also contribute to the effects elicited by chemogenetic interventions (Wright and Groenewegen, 1996;Reynolds and Zahm, 2005;Stachniak et al, 2014).…”

Section: Discussionmentioning

confidence: 53%

Activity of Insula to Basolateral Amygdala Projecting Neurons is Necessary and Sufficient for Taste Valence Representation

Kayyal¹,

Yiannakas²,

Chandran³

et al. 2019

J. Neurosci.

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Conditioned taste aversion (CTA) is an associative learning paradigm, wherein consumption of an appetitive tastant (e.g., saccharin) is paired to the administration of a malaise-inducing agent, such as intraperitoneal injection of LiCl. Aversive taste learning and retrieval require neuronal activity within the anterior insula (aIC) and the basolateral amygdala (BLA). Here, we labeled neurons of the aIC projecting to the BLA in adult male mice using a retro-AAV construct and assessed their necessity in aversive and appetitive taste learning. By restricting the expression of chemogenetic receptors in aIC-to-BLA neurons, we demonstrate that activity within the aICto-BLA projection is necessary for both aversive taste memory acquisition and retrieval, but not for its maintenance, nor its extinction. Moreover, inhibition of the projection did not affect incidental taste learning per se, but effectively suppressed aversive taste memory retrieval when applied either during or before the encoding of the unconditioned stimulus for CTA (i.e., malaise). Remarkably, activation of the projection after novel taste consumption, without experiencing any internal discomfort, was sufficient to form an artificial aversive taste memory, resulting in strong aversive behavior upon retrieval. Our results indicate that aIC-to-BLA projecting neurons are an essential component in the ability of the brain to associate taste sensory stimuli with body states of negative valence and guide the expression of valence-specific behavior upon taste memory retrieval.

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Section: Discussionmentioning

confidence: 53%

Activity of Insula to Basolateral Amygdala Projecting Neurons is Necessary and Sufficient for Taste Valence Representation

Kayyal¹,

Yiannakas²,

Chandran³

et al. 2019

J. Neurosci.

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“…A previous electrophysiological study showed that CTA learning enhances the functional connectivity between the IC and BLA [ 24 ]. In the IC, LTP is induced by the high frequency stimulation of BLA, which modulates CTA memory formation [ 18 – 22 ]. Recently, it is shown that IC-to-BLA projecting neurons are an essential components of the CTA acquisition and memory retrieval [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

“…The IC and BLA are reciprocally connected, and these interconnections are important for the retention of CTA memory [ 17 ]. It has also been shown that high frequency stimulation of the BLA induces long-term potentiation (LTP) in the IC, and the induction of LTP in the BLA-IC pathway before CTA training increases the retention of memory [ 18 – 22 ]. In addition, CTA training induces subsequent LTP in the BLA-IC pathway and increases amygdala-cortical function connectivity [ 23 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

Cortico-amygdala interaction determines the insular cortical neurons involved in taste memory retrieval

et al. 2020

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The insular cortex (IC) is the primary gustatory cortex, and it is a critical structure for encoding and retrieving the conditioned taste aversion (CTA) memory. In the CTA, consumption of an appetitive tastant is associated with aversive experience such as visceral malaise, which results in avoidance of consuming a learned tastant. Previously, we showed that levels of the cyclic-AMP-response-element-binding protein (CREB) determine the insular cortical neurons that proceed to encode a conditioned taste memory. In the amygdala and hippocampus, it is shown that CREB and neuronal activity regulate memory allocation and the neuronal mechanism that determines the specific neurons in a neural network that will store a given memory. However, cellular mechanism of memory allocation in the insular cortex is not fully understood. In the current study, we manipulated the neuronal activity in a subset of insular cortical and/or basolateral amygdala (BLA) neurons in mice, at the time of learning; for this purpose, we used an hM3Dq designer receptor exclusively activated by a designer drug system (DREADD). Subsequently, we examined whether the neuronal population whose activity is increased during learning, is reactivated by memory retrieval, using the expression of immediate early gene c-fos. When an hM3Dq receptor was activated only in a subset of IC neurons, c-fos expression following memory retrieval was not significantly observed in hM3Dq-positive neurons. Interestingly, the probability of c-fos expression in hM3Dq-positive IC neurons after retrieval was significantly increased when the IC and BLA were co-activated during conditioning. Our findings suggest that functional interactions between the IC and BLA regulates CTA memory allocation in the insular cortex, which shed light on understanding the mechanism of memory allocation regulated by interaction between relevant brain areas.

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“…We next employed our scRNA-seq dataset of mouse hippocampus (from CAG-CreERT2-ODD::R26R-tdTomato mice) collected upon normoxia (21% O 2 ) versus inspiratory hypoxia (6% O 2 for six hours/day) for five consecutive days (compare Figure 1 b; GSE162079 [ 7 ]), to evaluate the hypoxia regulation of all cells expressing the CaMKIIα-promoter. In the first step, we selected all glutamatergic neuronal populations (including mossy fiber cells), known to express CaMKIIα [ 12 , 13 , 14 , 15 ] from the hippocampal dataset and compared the expression levels of CaMKIIα under normoxic and hypoxic conditions ( Figure 6 a). Surprisingly, CaMKIIα was consistently upregulated under hypoxia in the excitatory neurons from the three discernible hippocampal regions (CA1, CA3, dentate gyrus).…”

Section: Resultsmentioning

confidence: 99%

CaMKIIα Expressing Neurons to Report Activity-Related Endogenous Hypoxia upon Motor-Cognitive Challenge

Butt

Hassouna

Garcia-Agudo

et al. 2021

IJMS

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We previously introduced the brain erythropoietin (EPO) circle as a model to explain the adaptive ‘brain hardware upgrade’ and enhanced performance. In this fundamental circle, brain cells, challenged by motor-cognitive tasks, experience functional hypoxia, triggering the expression of EPO among other genes. We attested hypoxic cells by a transgenic reporter approach under the ubiquitous CAG promoter, with Hif-1α oxygen-dependent degradation-domain (ODD) fused to CreERT2-recombinase. To specifically focus on the functional hypoxia of excitatory pyramidal neurons, here, we generated CaMKIIα-CreERT2-ODD::R26R-tdTomato mice. Behavioral challenges, light-sheet microscopy, immunohistochemistry, single-cell mRNA-seq, and neuronal cultures under normoxia or hypoxia served to portray these mice. Upon complex running wheel performance as the motor-cognitive task, a distinct increase in functional hypoxic neurons was assessed immunohistochemically and confirmed three-dimensionally. In contrast, fear conditioning as hippocampal stimulus was likely too short-lived to provoke neuronal hypoxia. Transcriptome data of hippocampus under normoxia versus inspiratory hypoxia revealed increases in CA1 CaMKIIα-neurons with an immature signature, characterized by the expression of Dcx, Tbr1, CaMKIIα, Tle4, and Zbtb20, and consistent with accelerated differentiation. The hypoxia reporter response was reproduced in vitro upon neuronal maturation. To conclude, task-associated activity triggers neuronal functional hypoxia as a local and brain-wide reaction mediating adaptive neuroplasticity. Hypoxia-induced genes such as EPO drive neuronal differentiation, brain maturation, and improved performance.

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CaMKII Requirement for in Vivo Insular Cortex LTP Maintenance and CTA Memory Persistence

Cited by 8 publications

References 59 publications

Activity of Insula to Basolateral Amygdala Projecting Neurons is Necessary and Sufficient for Taste Valence Representation

Activity of Insula to Basolateral Amygdala Projecting Neurons is Necessary and Sufficient for Taste Valence Representation

Cortico-amygdala interaction determines the insular cortical neurons involved in taste memory retrieval

CaMKIIα Expressing Neurons to Report Activity-Related Endogenous Hypoxia upon Motor-Cognitive Challenge

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