Evidence map›Paper›PMID 38082417›Full record

ArticleBiology of sex differences2023

Sex differences in mouse infralimbic cortex projections to the nucleus accumbens shell.

Caroline S Johnson, Andrew D Chapp, Erin B Lind, Mark J Thomas, Paul G Mermelstein

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Article in Biology of sex differences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Caroline S Johnson *Department of Neuroscience, School of Medicine, University of Minnesota, 4-140 Jackson Hall, 321 Church St SE, Minneapolis, MN, 55455, USA.ORCID 0000-0002-9439-8712
Andrew D Chapp *Department of Neuroscience, School of Medicine, University of Minnesota, 4-140 Jackson Hall, 321 Church St SE, Minneapolis, MN, 55455, USA.
Erin B Lind *Department of Neuroscience, School of Medicine, University of Minnesota, 4-140 Jackson Hall, 321 Church St SE, Minneapolis, MN, 55455, USA.
Mark J ThomasDepartment of Neuroscience, School of Medicine, University of Minnesota, 4-140 Jackson Hall, 321 Church St SE, Minneapolis, MN, 55455, USA.
Paul G MermelsteinDepartment of Neuroscience, School of Medicine, University of Minnesota, 4-140 Jackson Hall, 321 Church St SE, Minneapolis, MN, 55455, USA. pmerm@umn.edu.

Funding

Viral Innovation CoreP30DA048742 · NIDA · UNIVERSITY OF MINNESOTA · PI Mark John Thomas · 2020 to 2026
$19.0M
NEUROSCIENCE TRAINING IN DRUG ABUSE RESEARCHT32DA007234 · NIDA · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Paul G Mermelstein, Jocelyn M Richard · 1986 to 2026
$10.9M
Estrogen Facilitation of Female Drug RelapseR01DA041808 · NIDA · UNIVERSITY OF MINNESOTA · PI MERMELSTEIN, PAUL G, THOMAS, MARK JOHN · 2016 to 2020
$2.0M
NIDA NIH HHS DA041808NIDA NIH HHS P30DA048742NIDA NIH HHS R01 DA041808NIDA NIH HHS T32 DA007234NIDA NIH HHS T32DA007234
6 · The paper itself

Abstract

backgroundThe nucleus accumbens (NAc) is an important region in motivation and reward. Glutamatergic inputs from the infralimbic cortex (ILC) to the shell region of the NAc (NAcSh) have been implicated in driving the motivation to seek reward through repeated action-based behavior. While this has primarily been studied in males, observed sex differences in motivational circuitry and behavior suggest that females may be more sensitive to rewarding stimuli. These differences have been implicated for the observed vulnerability in women to substance use disorders.

methodsWe used an optogenetic self-stimulation task in addition to ex vivo electrophysiological recordings of NAcSh neurons in mouse brain slices to investigate potential sex differences in ILC-NAcSh circuitry in reward-seeking behavior. Glutamatergic neurons in the ILC were infected with an AAV delivering DNA encoding for channelrhodopsin. Entering the designated active corner of an open field arena resulted in photostimulation of the ILC terminals in the NAcSh. Self-stimulation occurred during two consecutive days of testing over three consecutive weeks: first for 10 Hz, then 20 Hz, then 30 Hz. Whole-cell recordings of medium spiny neurons in the NAcSh assessed both optogenetically evoked local field potentials and intrinsic excitability.

resultsAlthough both sexes learned to seek the active zone, within the first day, females entered the zone more than males, resulting in a greater amount of photostimulation. Increasing the frequency of optogenetic stimulation amplified female reward-seeking behavior. Males were less sensitive to ILC stimulation, with higher frequencies and repeated days required to increase male reward-seeking behavior. Unexpectedly, ex vivo optogenetic local field potentials in the NAcSh were greater in slices from male animals. In contrast, female medium-spiny neurons (MSNs) displayed significantly greater intrinsic neuronal excitability.

conclusionsTaken together, these data indicate that there are sex differences in the motivated behavior driven by glutamate within the ILC-NAcSh circuit. Though glutamatergic signaling was greater in males, heightened intrinsic excitability in females appears to drive this sex difference.

Indexed as

Nucleus AccumbensSex CharacteristicsAnimalsCerebral CortexFemaleHumansMaleMiceNeuronsGlutamateInfralimbic cortexIntracranial self-stimulationIntrinsic excitabilityMotivationNucleus accumbens shellOptogeneticsRewardSex differencesSynaptic strength

Identifiers

PMID38082417
PMCPMC10712109

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.