Dorsal-CA1 Hippocampal Neuronal Ensembles Encode Nicotine-Reward Contextual Associations

Abstract

Summary Natural and drug rewards increase the motivational valence of stimuli in the environment through Pavlovian learning mechanisms, becoming conditioned stimuli that directly motivate behavior in the absence of an original unconditioned stimulus. While the hippocampus has received extensive attention for its role in learning and memory processes, less is known regarding its role in drug-reward associations. We used in vivo Ca2+ imaging in freely moving mice during the formation of nicotine preference behavior to examine the role of the dorsal-CA1 region of the hippocampus in encoding contextual reward-seeking behavior. We show the development of specific neuronal ensembles whose activity encodes nicotine-reward contextual memories and which are necessary for the expression of place preference. Our findings increase our understanding of CA1 hippocampal function in general, and as it relates to reward processing by identifying a critical role for CA1 neuronal ensembles in nicotine place preference.

Impaired hypocretin/orexin system alters responses to salient stimuli in obese male mice

“…The hippocampus is essential for numerous cognitive behaviors. In particular, the dorsal hippocampus is critical for learning the context-drug association measured in drug-seeking behaviors, such as conditioned place preference (CPP) (48)(49)(50)(51)(52)(53). Similarly, active coping in the forced swim paradigm also requires intact hippocampal activity (54)(55)(56)(57).…”

Tracking the Same Neurons across Multiple Days in Ca2+ Imaging Data

“…Furthermore, since one-photon microscopy mostly reveals transient and localized changes in fluorescence that exceed the background noise, a cell must be active to be detected. Thus, the set of detected cells can differ between sessions ( Ziv et al., 2013 , Resendez et al., 2016 , Grewe et al., 2017 , Xia et al., 2017 ), and a one-to-one mapping of neural identity across sessions is typically not attainable. Taken together, these factors introduce uncertainty and, consequently, potential errors to the cell registration procedure.…”

Leveraging calcium imaging to illuminate circuit dysfunction in addiction

“…When this analysis is implemented with cellular resolution imaging, population responses can be assessed (e.g., x number of cells are responsive to tone A, y number of cells are responsive to tone B) (e.g., Livneh et al, 2017 ). An example of the way a peri-stimulus time histograms are used is comparing the neural response across trials when animals are exposed to drug-paired cues as opposed to neutral cues ( Calipari et al, 2016 ; Xia et al, 2017 ). While these commonly implemented approaches are highly useful and are a great starting point for analyses, experiments often call for more specialized and complex analyses, which must be dealt with on a case-by-case basis.…”

“…Several commercially produced systems, as well as open-source options, are now available, making calcium-imaging technology easily accessible outside the optics field. Laboratories have readily adopted these approaches to investigate the neurobiology of addiction in rodent models ( Beier et al, 2017 ; Calipari et al, 2017 , 2016 ; Luo, Volkow, Heintz, Pan, & Du, 2011 ; Xia, Nygard, Sobczak, Hourguettes, & Bruchas, 2017 ).…”