Journal article
Infralimbic projections to the nucleus accumbens shell and amygdala regulate the encoding of cocaine extinction learning
The Journal of neuroscience, Vol.43(8), pp.1348-1359
02/22/2023
DOI: 10.1523/JNEUROSCI.2023-22.2022
PMCID: PMC9987566
PMID: 36657972
Abstract
Prior evidence indicates that the infralimbic cortex (IL) mediates the ongoing inhibition of cocaine seeking following self-administration and extinction training in rats, specifically through projections to the nucleus accumbens (NA) shell. Our own data indicate that IL activity immediately following an unreinforced lever press is critical for encoding the extinction contingencies in such procedures. Whether extinction encoding requires activity in the IL exclusively or also activity in its outputs, such as those to the NAshell and amygdala, is unknown. To address this issue, we used a closed-loop optogenetic approach in female and male Sprague-Dawley rats to silence IL-NAshell or IL-amygdala activity following an unreinforced lever press during extinction training. Optical illumination (20 s) was given either immediately after a lever press or following a 20 s delay. IL-NAshell inhibition immediately following an unreinforced lever press increased lever pressing during extinction training and impaired retention of extinction learning, as assessed during subsequent extinction sessions without optical inhibition. Likewise, IL-amygdala inhibition given in the same manner impaired extinction retention during sessions without inhibition. Control experiments indicate that critical encoding of extinction learning does not require activity in these pathways beyond the initial 20 s post-lever press period, as delayed IL-NAshell and IL-amygdala inhibition had no effect on extinction learning. These results suggest that a larger network extending from the IL to the NAshell and amygdala is involved in encoding extinction contingencies following cocaine self-administration.
Infralimbic cortex (IL) activity following an unreinforced lever press during extinction learning encodes the extinction of cocaine-seeking behavior. However, the larger circuitry controlling such encoding has not been investigated. Using closed-loop optogenetic pathway targeting, we found that inhibition of IL projections to the nucleus accumbens (NA) shell and to the amygdala impaired the extinction of cocaine seeking. Importantly, these effects were only observed when activity was disrupted during the first 20 s post-lever press and not when given following a 20 s delay. These findings suggest that successful cocaine extinction encoding requires activity across a larger circuit beyond simply inputs to the IL.
Details
- Title: Subtitle
- Infralimbic projections to the nucleus accumbens shell and amygdala regulate the encoding of cocaine extinction learning
- Creators
- Kelle E Nett - University of IowaAlexa R Zimbelman - Department of Psychological and Brain Sciences, University of Iowa, Iowa City, IA 52242Matthew S McGregor - Interdisciplinary Neuroscience Program, University of Iowa, Iowa City, IA 52242Vanessa Alizo Vera - Department of Psychological and Brain Sciences, University of Iowa, Iowa City, IA 52242Molly Harris - Department of Psychological and Brain Sciences, University of Iowa, Iowa City, IA 52242Ryan T LaLumiere - University of Iowa
- Resource Type
- Journal article
- Publication Details
- The Journal of neuroscience, Vol.43(8), pp.1348-1359
- DOI
- 10.1523/JNEUROSCI.2023-22.2022
- PMID
- 36657972
- PMCID
- PMC9987566
- ISSN
- 0270-6474
- eISSN
- 1529-2401
- Grant note
- DOI: 10.13039/100000002, name: HHS | National Institutes of Health, award: DA049139, DA048055
- Language
- English
- Electronic publication date
- 01/16/2023
- Date published
- 02/22/2023
- Academic Unit
- Psychological and Brain Sciences; Iowa Neuroscience Institute
- Record Identifier
- 9984362759102771
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