Olfactory circuit changes underlying odor memory

NIH RePORTER · NIH · F32 · $50,154 · view on reporter.nih.gov ↗

Abstract

Summary Odor perception and hedonics are highly intermeshed at both the behavioral and neural circuit level in humans and non-human animals. This association may in part reflect the fact that the piriform cortex (PCX) is particularly tightly linked with the amygdala. Amygdala projections from the lateral, basal, accessory basal, and posterior cortical nuclei as well as the periamygdaloid cortex of the amygdala target both the posterior PCX (and to a lesser extent the anterior PCX), with the PCX sending reciprocal connections back to the amygdala. The basolateral amygdala (BLA) is required for odor fear learning, and work from our lab has shown that PCX odor responses are shaped by both fear learning and by BLA input. For example, discriminative odor fear conditioning involving both a CS+ and CS- results in odor-specific learned fear responses, as well as narrowing of PCX single-unit odor receptive fields (i.e., enhanced PCX odor acuity). This modification of PCX odor coding may be due to input from the BLA since optogenetic activation of BLA fibers within the PCX can modify single-unit and single-unit ensemble odor responses in anesthetized rodents. The BLA may exert this modulation of the PCX through its glutamatergic projections which target both excitatory pyramidal cells and inhibitory interneurons in the PCX. Finally, odor fear memory is shaped by post- conditioning sleep-dependent consolidation. Interestingly, manipulations of PCX activity during post- conditioning slow-wave sleep can influence both the strength and the accuracy of learned fear responses. However, how the BLA and PCX work in tandem to shape PCX odor coding and hedonics is unknown. Here, using high precision spatiotemporal manipulations and single-unit ensemble recordings in freely moving animals, I will dissect the BLA-PCX circuit before, during, and after animals learn hedonic associations with an odor. I will assess the BLA’s role in shaping both the strength and acuity of learned odor responses at both the behavioral and PCX single-unit ensemble levels. The proposed work is comprised of three specific aims. Aim 1 will test the hypothesis that BLA input to the PCX is required for acquisition of an odor-specific learned fear response and associated changes in PCX odor coding. Aim 2 will test the hypothesis that BLA input to the PCX is required during post-conditioning slow-wave sleep for consolidation of odor-specific learned fear response and associated changes in PCX odor coding. Aim 3 will test the hypothesis that BLA input to the PCX is required for expression of an odor-specific learned fear response. The techniques required to successfully complete these proposed experiments will also represent a significant advancement of my technical and analytical skill set to use in my future research career. Beyond mere technical skills, the proposed work also allows me to expand my knowledge of the field and literature into both new brain systems (i.e. piriform cortex and amygd...

Key facts

NIH application ID
9966949
Project number
5F32DC017356-03
Recipient
NATHAN S. KLINE INSTITUTE FOR PSYCH RES
Principal Investigator
Brett S East
Activity code
F32
Funding institute
NIH
Fiscal year
2020
Award amount
$50,154
Award type
5
Project period
2018-07-01 → 2021-02-28