Abstract
The complex system of learning and memory are better understood by examining molecular and physiological changes. These changes occur in different brain regions to elicit the formation or recall of a memory. Because mice are the most commonly used vertebrate in biomedical neuroscience research (Kandel et al., 2014) and are used to explore the intricacies of memory through mutants (Grant et al., 1992; Morris et al., 1986; Silva et al., 1992) we use them here to understand the molecular players of learning and memory in the Basolateral Amygdala (BLA) because of the physiological relevance to taste behavior. The genetics of mice are also flexible enough for manipulation of molecular changes at the level of specific neuronal populations.\r It is advantageous for an animal to learn to avoid noxious stimuli that it encounters in the world. We can use this behavior as an experimental paradigm to understand the molecular and cellular mechanisms at play when the animal attempts to learn this behavior. Conditioned Taste Aversion (CTA) is a robust one-trial instance of learning whereby a conditioned stimulus, (CS) taste, is paired with an Unconditioned Stimulus, (US) malaise(Garcia et al., 1955; Yamamoto et al., 1994). Chemogenetic manipulation, as well as biochemistry, electrophysiology, and behavior, can be observed to further understand memory in the mice model. \r It is generally understood, through prior research, that molecular changes must take place when an animal undergoes long-term memory (LTM) formation (Alberini, 2009; Kandel, 2001). Furthermore, these molecular changes can lead to alteration in cellular and synaptic properties such as excitability. (Mozzachiodi and Byrne, 2010; Zhang and Linden, 2003).\r Building upon previous work from members of the lab identifying some of the important molecular players of CTA (Levitan et al., 2019), this body of work sought to explore a mechanism of aversion memory not fully understood. Two important genes involved in CTA were identified, Serine Threonine Kinase 11 (STK11) and the immediate early gene c-Fos. Utilizing Fluorescent In-Situ Hybridization (FISH) we can visualize and localize mRNA transcripts (Levsky and Singer, 2003) to better understand which cells express specific gene transcript. Through conditional knockout (cKO) of STK11 in BLA, CTA memory is completely blocked This knockout increases excitability of BLA projection neurons but the action on memory could be through a mechanism not yet explored. cKO of Fos will also impair learning and increases excitability of these cells. Conversely, cells activated by CTA show a lower excitability. We set out to test the causal relationship between BLA projection neuron excitability and CTA. Artificially increasing those cell’s excitability impair CTA learning in mice. Together, this data suggest that these two molecules play a role in CTA memory formation through the intrinsic excitability of projection neurons in the Basolateral Amygdala.