Synaptic organization and plasticity of the input from the basolateral amygdala t

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DESCRIPTION (provided by applicant): The gustatory cortex (GC) receives modulatory inputs from multiple regions of the limbic system. Lateral hypothalamus, medial prefrontal cortex, mediodorsal thalamus and basolateral amygdala (BLA) are all known to send projections to GC (Saper 1982; Allen, Saper et al. 1991; Maffei, Haley et al. 2012). Among these inputs, those from the BLA are the ones whose functional significance has been studied the most. Pharmacological and electrophysiological experiments in alert animals have suggested that inputs from BLA are necessary for GC to process information pertaining to the hedonic value of gustatory stimuli (Piette, Baez- Santiago et al. 2012) and the anticipatory value of taste-predictive cues (Samuelsen, Gardner et al. 2012). In addition, plastic changes of the BLA-GC connection have been associated with taste aversion learning (Guzman-Ramos and Bermudez-Rattoni 2012). Despite the abundance of studies investigating the functional role of the BLA-GC connection (Jones, French et al. 1999; Grossman, Fontanini et al. 2008; Guzman-Ramos and Bermudez-Rattoni 2012; Piette, Baez- Santiago et al. 2012; Parkes and Balleine 2013), very little is known on the synaptic organization and plasticity of these inputs. Evidence from intracellular and extracellular recordings in vivo suggests that BLA-GC inputs might exert complex excitatory as well as inhibitory actions (Yamamoto, Azuma et al. 1984; Hanamori 2009; Stone, Maffei et al. 2011), yet no information is available on the synaptic mechanisms underlying these effects. Furthermore, while analysis of BLA evoked potentials in GC provides evidence for learning-related plasticity at this connection (Escobar, Chao et al. 1998; Jones, French et al. 1999; Escobar and Bermudez-Rattoni 2000; Rodriguez-Duran, Castillo et al. 2011), the mechanisms, rules and postsynaptic targets of this plasticity are unknown. Until recently it has been impossible to selectively activate BLA afferents in vitro to finely dissect th GC circuits recruited by amygdalar inputs. The availability of optogenetic tools has however changed the situation (Zhang, Gradinaru et al. 2010; Stuber, Sparta et al. 2011; Yizhar, Fenno et al. 2011; Britt and Bonci 2013; Wang, Kloc et al. 2013), finally allowing us the fundamental questions pertaining to the synaptic organization of amygdalar afferents to GC to be addressed. The experiments proposed here rely on these novel techniques, combined with in vitro whole cell patch clamp recordings, to directly measure the properties of amygdalar synapses onto pyramidal cells and inhibitory interneurons in GC. This methodological approach will be complemented with pharmacological and behavioral manipulations to test the following hypotheses: 1) BLA afferents make direct functional synapses onto different cell types within GC local circuits; 2) Synaptic inputs onto pyramidal neurons and inhibitory interneurons show activity-dependent plasticity; 3) The strength of BLA- GC synapses is affected by hedonic learning. Altogether these experiments will allow us to investigate the synaptic organization of BLA-GC inputs, their plasticity and the changes associated with aversion learning. This framework represents an entirely novel approach to the study of GC inputs in brain slices and promises to provide the first circuit-level description of amygdalar synapses in the gustatory cortex.