Employing holographic stimulation to probe the cellular basis of the engram for odor epochs.

NIH RePORTER · NIH · F31 · $37,659 · view on reporter.nih.gov ↗

Abstract

In the natural world, animals rely heavily on their sense of smell to safely navigate their environment, and experimentally mice can be taught complex decision-making tasks which rely on the animal's ability to integrate experience and olfactory stimulus. Association of context and olfactory stimuli is thought to be achieved through the encoding and retrieval of memories through the hippocampus. The hippocampus, a curved structure nestled deep within the temporal lobe of the brain, serves three primary functions: the regulation of emotions, formation of new memories, and memory retrieval. It plays a vital role in the creation, organization, and retention of fresh memories, as well as in linking certain sensations and emotions (valence) to these memories. The dorsal and ventral hippocampus regions have been implicated in acquisition, consolidation, and retrieval of temporal information in optogenetic stimulation of trace fear conditioning by a significant number of studies and importantly, lesions to dorsal CA1 (dCA1) result in impaired memory retrieval. Calbindin 2 pyramidal cells in dCA1 have additionally been implicated in learning during the go-no go associative discrimination task, as inhibition slows learning. Interestingly, within dCA1 exists a population of pyramidal cells that during the go-no go associative learning task demonstrate divergent stimulus responses, which take place at discrete times during the go-no go task, thereby exhibiting ‘time tiling’. This can be thought of as temporally discrete divergence in activity related to stimulus valence and are called ‘decision-predicting time cells’. With the recent discovery of decision-predicting time cells, there is currently no literature investigating their molecular composition, their influence on behavior, and their interactions with interneurons. Of note, it has been demonstrated that PV interneurons play crucial roles not only in regulating the excitability of cell populations, but also in providing precisely timed inhibitory input. Currently, no studies have characterized the roles of parvalbumin-positive interneurons in dCA1 hippocampus during complex olfactory discrimination tasks, particularly related to decision-predicting time cells. Aim 1 will probe if decision-predicting time cells and calbindin 2 positive and utilize advanced optical techniques such as two-photon holographic stimulation to selectively impair divergent time tiled responses. Aim 2 will characterize the role of PV interneurons related to decision-predicting time cell activity and determine the effect on licking behavior and accuracy during the go-no go olfactory task if PV interneurons are inhibited during the task.

Key facts

NIH application ID
11070789
Project number
1F31DC022171-01A1
Recipient
UNIVERSITY OF COLORADO DENVER
Principal Investigator
Kira A Steinke
Activity code
F31
Funding institute
NIH
Fiscal year
2024
Award amount
$37,659
Award type
1
Project period
2024-08-01 → 2027-07-31