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=Grant Procedure Text=
see Houpt RO1 ResearchStrategy2014 for more text
Conditioned taste aversion (CTA) is a robust form of associative learning in which an animal avoids and reacts aversively to the taste of a food that has been previously paired with illness. CTA is a rich behavioral phenomenon with many of the characteristics of classical conditioning, but with additional unique features such as single-trial learning, long-delay learning, learned safety, taste specificity, and olfactory potentiation [1]. CTA allows integration of gustation with manifold unconditioned stimuli such as ionizing radiation [2], gastrointestinal toxins [3], chemotoxins [4], visual optokinetic stimuli [5], and vestibular perturbation [6,7]. Neurologically, CTA belongs to the class of indirect controls of feeding, by which a distributed forebrain-hindbrain network modulates the direct responses of the brainstem to taste stimulation [1,9]. The robust conditioned change of behavioral responses to tastes in CTA serves as model of a learned control of ingestion.
While CTA has unique adaptations subserving ingestive learning, it presents features of relevance to the general neurobiology of learning. Like fear conditioning, CTA is an amygdala-dependent form of traumatic memory that is rapidly acquired and extremely persistent. Acquisition of CTA is NMDA-receptor mediated, and sensitive to tauopathy. There is considerable overlap of intracellular signaling pathways in CTA with other models of plasticity (i.e. kinases, adaptor proteins, and transcription factors). T unique neuroanatomical and temporal properties of CTA learning permit easier manipulation of intracellular pathways and quantification of the behavioral consequences. Relevant to this proposal, CTA learning is compromised in several mouse and rat models of AD.
== CTA Conditioning and Assessment==
We will employ a standard procedure for conditioning and assessing CTA: The Conditioned Stimulus (CS) is an innately preferred but non-nutritive tastant (0.125% saccharin) presented by 1-bottle access (10min) or intraoral infusion (6 ml/6min). Prior to conditioning, animals are water restricted at 10-min access per day to guarantee ingestion on conditioning day. The Unconditioned Stimulus (US) will be a moderate dose of toxin (e.g. (18-36 mg/kg LiCl, ip, or 7.5 mg/kg apomorphine hydrochloride i.p.) that will allow observation of either potentiation or attenuation of CTA by Li deficiency or supplementation.. The CS-US interval will be 30-min from the start of the CS to the time of US injection, thereby modeling long- delay CTA learning. Depending on the manipulation, the CS-US interval may be probed by administering the treatment during the CS-US interval (e.g. injection of inhibitors 15 min after the CS but before the US). Expression Tests will measure the initial magnitude and rate of extinction of a CTA using 24-h, 2-bottle preference tests of CS vs. water across 14 days post-acquisition. Bar-coded bottles and computer-assisted weighing allows monitoring of up to 96 animals per day. We operationally define a CTA as a significantly lower CS preference (24-h saccharin intake/total intake) compared to controls. When examining short-term effects, intraoral infusions (6 ml/6min) will be used to precisely deliver the CS, 0-6 h after the US [97].
=Scope=
=Scope=
''This article describes some of the fundamental behavioral properties of conditioned taste aversion learning. The article is a work in progress -- in particular, no specific citations are provided yet.''
''This article describes some of the fundamental behavioral properties of conditioned taste aversion learning. The article is a work in progress -- in particular, no specific citations are provided yet.''