Probing for Conditioned Hallucinations Through Neural Activation in a Ketamine Mouse Model of Schizophrenia

Variables influencing conditioning-evoked hallucinations: overview and future applications

“…Interestingly, DISC-1 mice showed significantly increased neural activity in the insular (gustatory) cortex following testing; suggesting disruptions in DISC-1 led to a pattern of brain activity similar to what would be expected if sucrose had actually been presented. A similar pattern of enhanced insular activity was revealed in ketamine-exposed mice that received mediated performance testing (Wu et al, 2020), whereby a sucrose solution was delivered in the presence of an almond odor. Subsequently, mice were exposed to the odor but sucrose was replaced with water.…”

“…Mediated learning procedures have been utilized to study the neurobiology of impaired reality testing in rodents (McDannald & Schoenbaum, 2009 ) and have been employed in several animal models of schizophrenia (Fry et al, 2020 ; Kim & Koh, 2016 ; Koh et al, 2018 ; McDannald et al, 2011 ; Wu, Haberman, Gallagher, & Koh, 2020 ) to yield insights into the neural circuits involved in hallucination-like phenomena in animals. McDannald et al ( 2011 ) were the first to employ mediated learning procedures in an animal model of schizophrenia.…”

“…Consistent with the previously described studies in humans (Stevenson et al, 1998 ), the almond flavor was capable of evoking activity in putative sweet-taste responsive cells in the insular cortex. This effect was significantly augmented in ketamine-exposed mice (Wu et al, 2020 ), thus indicating that both auditory (Fry et al, 2020 ) and olfactory (Wu et al, 2020 ) CSs can evoke robust taste percepts in animal models of schizophrenia. This latter study also indicated that insular activity could be further enhanced by hippocampal lesions (Wu et al, 2020 ), which together with the necessity of CB1R in hippocampal GABAergic cells (Busquets-Garcia et al, 2018 ), and basolateral amygdala in representation mediated learning (Dwyer & Killcross, 2006 ; Johnson, Gallagher, & Holland, 2009 ), suggests a critical role for the limbic system in perpetuating psychotic-like behaviors in animal models.…”

“…This effect was significantly augmented in ketamine-exposed mice (Wu et al, 2020 ), thus indicating that both auditory (Fry et al, 2020 ) and olfactory (Wu et al, 2020 ) CSs can evoke robust taste percepts in animal models of schizophrenia. This latter study also indicated that insular activity could be further enhanced by hippocampal lesions (Wu et al, 2020 ), which together with the necessity of CB1R in hippocampal GABAergic cells (Busquets-Garcia et al, 2018 ), and basolateral amygdala in representation mediated learning (Dwyer & Killcross, 2006 ; Johnson, Gallagher, & Holland, 2009 ), suggests a critical role for the limbic system in perpetuating psychotic-like behaviors in animal models. Evidence from non-human primates has also demonstrated the necessity of limbic structures in using detailed reinforcer representations to guide behavior (Baxter, Parker, Lindner, Izquierdo, & Murray, 2000 ; Málková, Gaffan, & Murray, 1997 ; West, DesJardin, Gale, & Malkova, 2011 ), suggesting that these results may generalize across higher-ordered mammalian species.…”

Using internal memory representations in associative learning to study hallucination-like phenomenon

“…Prior research importantly has shown the cued activation of the taste area in the insular cortex to resemble natural neural representation of taste stimuli (Saddoris et al, 2009), and stimulation of the taste cortex in the absence of an actual taste can initiate taste percepts to guide behavior (Peng et al, 2015). In our experiment using a ketamine mouse model of schizophrenia, mice received odor-taste compound exposures, and then odor exposure alone (with water to drink) aimed at activating a taste representation (Wu et al, 2020). We found that the previously taste-associated odor induced a stronger neural activation in the insular taste cortex in mice exposed to ketamine during adolescence than control mice.…”