Extinction of conditioned taste aversion is related to the aversion strength and associated with c-fos expression in the insular cortex

Hadamitzky, Martin; Bösche, Katharina; Engler, Andrea; Schedlowski, Manfred; Engler, Harald

doi:10.1016/j.neuroscience.2015.06.040

Cited by 30 publications

(32 citation statements)

References 49 publications

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“…Further examination of the Figure 3A c-Fos data largely conformed to expectation. A significant difference between training-session c-Fos observed in WPE-CTA and WPE-sham rats (Fisher's LSD, p = 0.044) replicated previous studies (Navarro et al 2000b;Koh and Bernstein 2005;Wilkins and Bernstein 2006;Hadamitzky et al 2015). The difference between the WPE-CTA and WPE-LiCl groups (Fisher's LSD, p = 0.549) failed to achieve significance here, but by far the simplest explanation for this lack of significance, which is of little import in the current study, is the fact that the current protocol was specifically designed to minimize it: measurements for each rat-one in an anterior GC slice, one in a middle GC slice, and one in a posterior GC slice ( Figure 4A; see Methods).…”

Section: Figuresupporting

confidence: 87%

“…Given that CTA learning has repeatedly been associated with increased levels of c-Fos expression in GC (Koh and Bernstein 2005;Hadamitzky et al 2015;Soto et al 2017), and that TPE enhances learning , we hypothesized that TPE would enhance learning-related c-Fos expression in GC. We therefore compared c-Fos in CTA-conditioned TPE rats to that of five controls: 1) rats that underwent the exact same CTA -conditioning procedure, but were preexposed only to water (i.e., WPE rats); 2-3) rats that received TPE or WPE, but for which the "training trial" was actually a "sham-training" trial in which sucrose was delivered was paired with harmless saline injection; and 4-5) rats that received TPE or WPE followed by "training" that consisted of LiCl alone (Figure 1).…”

Section: Figurementioning

confidence: 99%

“…While much remains to be learned about this behavioral phenomenon, the above results do enable us to formulate basic hypotheses regarding how sensory taste information acquired during TPE is processed in the brain and integrated into future learning. An appropriate place to start in this regard is with primary gustatory cortex (GC), which resides in the anterior insula: GC has been amply shown, in electrophysiological studies (Katz et al 2001;Grossman et al 2008; Moran and Katz 2014;Sadacca et al 2016), immediate early gene imaging (Desmedt et al 2003;Contreras et al 2007;Inberg et al 2013;Uematsu et al 2015), and loss of function experiments (Berman and Dudai 2001;Stehberg and Simon 2011;Levitan et al 2016a;Levitan et al 2016b;Li et al 2016) to play a role in mediating taste behavior and CTA learning, as well as taste novelty/familiarity (Gallo et al 1992;Rosenblum et al 1993;Koh et al 2003;Bahar et al 2004;Koh and Bernstein 2005;Roman and Reilly 2007;Merhav and Rosenblum 2008;Nunez-Jaramillo et al 2008;Lin et al 2012c;Inberg et al 2013;Hadamitzky et al 2015). Here, we test the hypothesis that GC is vital for representing incidental taste experience and for driving the impact of that experience on later CTA learning.…”

Section: Introductionmentioning

confidence: 99%

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The role of the gustatory cortex in incidental experience-evoked enhancement of later taste learning

Flores

Parmet

Mukherjee

et al. 2018

Preprint

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The strength of learned associations between pairs of stimuli is affected by multiple factors, the most extensively studied of which is prior experience with the stimuli themselves. In contrast, little data is available regarding how experience with incidental stimuli (independent of any conditioning situation) impacts later learning. This lack of research is striking given the importance of incidental experience to survival. We have recently begun to fill this void using conditioned taste aversion (CTA), wherein an animal learns to avoid a taste that has been associated with malaise. We previously demonstrated that incidental exposure to salty and sour tastes (taste pre-exposure-TPE) enhances aversions learned later to sucrose.Here, we investigate the neurobiology underlying this phenomenon. First, we use immediate early gene (c-Fos) expression to identify gustatory cortex (GC) as a site at which TPE specifically increases the neural activation caused by taste-malaise pairing (i.e., TPE did not change c-Fos induced by either stimulus in isolation). Next, we use site-specific infection with the optical silencer Archaerhodopsin-T to show that GC inactivation during TPE inhibits the expected enhancements of both learning and CTA-related c-Fos expression, a full day later. Thus, we conclude that GC is almost certainly a vital part of the circuit that integrates incidental experience into later associative learning.

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Section: Figuresupporting

confidence: 87%

Section: Figurementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The role of the gustatory cortex in incidental experience-evoked enhancement of later taste learning

Flores

Parmet

Mukherjee

et al. 2018

Preprint

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“…22 Indeed, c-Fos is widely used as an activity indicator in many studies measuring taste induced activity in the central taste system. 48, 49, 50 A spike in c-Fos immunoreactivity in the central amygdala and insular cortex regions of brain was observed during taste aversion conditioning and on introduction of novel tastants. 51 Other work reported that c-Fos KO animals have deficits in the normal long-term learning and memory that is normally associated with aversive taste learning.…”

Section: Discussionmentioning

confidence: 99%

AP1 transcription factors are required to maintain the peripheral taste system

et al. 2016

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The sense of taste is used by organisms to achieve the optimal nutritional requirement and avoid potentially toxic compounds. In the oral cavity, taste receptor cells are grouped together in taste buds that are present in specialized taste papillae in the tongue. Taste receptor cells are the cells that detect chemicals in potential food items and transmit that information to gustatory nerves that convey the taste information to the brain. As taste cells are in contact with the external environment, they can be damaged and are routinely replaced throughout an organism's lifetime to maintain functionality. However, this taste cell turnover loses efficiency over time resulting in a reduction in taste ability. Currently, very little is known about the mechanisms that regulate the renewal and maintenance of taste cells. We therefore performed RNA-sequencing analysis on isolated taste cells from 2 and 6-month-old mice to determine how alterations in the taste cell-transcriptome regulate taste cell maintenance and function in adults. We found that the activator protein-1 (AP1) transcription factors (c-Fos, Fosb and c-Jun) and genes associated with this pathway were significantly downregulated in taste cells by 6 months and further declined at 12 months. We generated conditional c-Fos-knockout mice to target K14-expressing cells, including differentiating taste cells. c-Fos deletion caused a severe perturbation in taste bud structure and resulted in a significant reduction in the taste bud size. c-Fos deletion also affected taste cell turnover as evident by a decrease in proliferative marker, and upregulation of the apoptotic marker cleaved-PARP. Thus, AP1 factors are important regulators of adult taste cell renewal and their downregulation negatively impacts taste maintenance.

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“…To our knowledge, this is the first study to show that the posterior insular cortex is involved in the retrieval of fear extinction memory in rodents. The insular cortex is important for the acquisition and extinction of conditioned taste aversion (16), and the extinction rate is positively correlated with c-fos messenger RNA expression in rats (17). Bilateral inhibition of the posterior insular cortex during stress exposure prevented the stress-mitigating effect of safety signals (18).…”

Section: Discussionmentioning

confidence: 99%

PET Mapping of Neurofunctional Changes in a Posttraumatic Stress Disorder Model

Zhu

et al. 2016

J Nucl Med

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Posttraumatic stress disorder (PTSD) is an anxiety disorder that occurs after exposure to a traumatic event. This study aimed to investigate the neurobiologic changes before and after exposure-based therapy by PET in a rat model of PTSD. Methods: Serial 18 F-FDG PET imaging studies were performed under the control (tone presentation), fear-conditioning, and extinction retrieval phases. Neuroactivity marker c-Fos protein was used for immunostaining. Results: Increased glucose metabolism was observed in the bilateral amygdala after fearconditioning (P , 0.001) and in the right posterior insular cortex under extinction retrieval (P , 0.001) compared with the control phase. Increased c-Fos expression in the posterior insular cortex under extinction retrieval was positively correlated to the glucose metabolism (P , 0.01). Conclusion: Our results indicated that the amygdala plays a key role in fear memory formation and, most importantly, the insular cortex is related to the retrieval of extinction memory. 18 F-FDG PET may provide a promising in vivo approach for evaluating exposurebased therapy of PTSD. Post traumatic stress disorder (PTSD) is the most costly psychiatric disorder, affecting up to 40% of individuals over lifetime exposure to traumatic events (1,2). Over the past decades, considerable studies have explored how fear memories are encoded in the brain. A neurocircuitry model of PTSD emphasized the importance of the amygdala, as well as its interactions with the ventral/ medial prefrontal cortex (PFC) and hippocampus (3). In accord with this model, initial neuroimaging studies of PTSD provided evidence for exaggerated amygdala responses and attenuated ventral/ medial PFC responses during exposure to reminders of the traumatic event (3). In addition, Pavlovian fear-conditioning studies highlighted the key role of the amygdala in the acquisition and storage of conditioned fear memories (4,5). Electrophysiologic recording and inactivation studies in rats suggest that fear extinction depended on increased neuroactivity in the medial PFC under extinction training (6,7). Furthermore, the amygdala has been found activated during fear acquisition (8) and positively correlated with the severity of PTSD symptoms (9). Failure to recall fear extinction memory is associated with lower activation in the hippocampus and ventral/medial PFC in PTSD patients relative to trauma-exposed healthy subjects (10).Although exposure-based therapy (conceptually based on fear extinction) has been widely used in the treatment of PTSD (1), its underlying mechanism has not been completely elucidated. Because PET has been increasingly used to characterize neural activities, we hypothesized that 18 F-FDG PET could be applied for evaluating cerebral glucose metabolism before and after exposure-based therapy and could provide a potential translational tool for future clinical applications. Thus, the present study aimed to investigate the neurobiologic changes by 18 F-FDG PET in a rat model of PTSD. MATERIALS AND METHODS AnimalsMale Sprague-Da...

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Extinction of conditioned taste aversion is related to the aversion strength and associated with c-fos expression in the insular cortex

Cited by 30 publications

References 49 publications

The role of the gustatory cortex in incidental experience-evoked enhancement of later taste learning

The role of the gustatory cortex in incidental experience-evoked enhancement of later taste learning

AP1 transcription factors are required to maintain the peripheral taste system

PET Mapping of Neurofunctional Changes in a Posttraumatic Stress Disorder Model

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