Sex differences in pre- and post-synaptic glutamate signaling in the nucleus accumbens core

Knouse, Melissa C.; Deutschmann, Andre U.; Nenov, Miroslav N.; Wimmer, Mathieu E.; Briand, Lisa A.

doi:10.1186/s13293-023-00537-4

Cited by 7 publications

(3 citation statements)

References 103 publications

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“…This suggests female mice may have an augmented perceived saliency of experiencing aversive stimuli. There is also evidence showing that female mice exhibit greater excitatory NAc core transmission compared to males 45 suggesting that female accumbal responses to external stimuli may be stronger at baseline. Overall, these results showing greater NAc core single cell response to experienced aversive stimuli in female mice add to the literature on sex differences in aversive learning processes.…”

Section: Discussionmentioning

confidence: 99%

Nucleus accumbens core single cell ensembles bidirectionally respond to experienced versus observed aversive events

Dinckol,

Wenger,

Zachry

et al. 2023

Sci Rep

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Fear learning is a critical feature of survival skills among mammals. In rodents, fear learning manifests itself through direct experience of the aversive event or social transmission of aversive stimuli such as observing and acting on conspecifics’ distress. The neuronal network underlying the social transmission of information largely overlaps with the brain regions that mediate behavioral responses to aversive and rewarding stimuli. In this study, we recorded single cell activity patterns of nucleus accumbens (NAc) core neurons using in vivo optical imaging of calcium transients via miniature scopes. This cutting-edge imaging methodology not only allows us to record activity patterns of individual neurons but also lets us longitudinally follow these individual neurons across time and different behavioral states. Using this approach, we identified NAc core single cell ensembles that respond to experienced and/or observed aversive stimuli. Our results showed that experienced and observed aversive stimuli evoke NAc core ensemble activity that is largely positive, with a smaller subset of negative responses. The size of the NAc single cell ensemble response was greater for experienced aversive stimuli compared to observed aversive events. Our results also revealed sex differences in the NAc core single cell ensembles responses to experience aversive stimuli, where females showed a greater accumbal response. Importantly, we found a subpopulation within the NAc core single cell ensembles that show a bidirectional response to experienced aversive stimuli versus observed aversive stimuli (i.e., negative response to experienced and positive response to observed). Our results suggest that the NAc plays a role in differentiating somatosensory experience from social observation of aversion at a single cell level. These results have important implications for psychopathologies where social information processing is maladaptive, such as autism spectrum disorders.

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Section: Discussionmentioning

confidence: 99%

Nucleus accumbens core single cell ensembles bidirectionally respond to experienced versus observed aversive events

Dinckol,

Wenger,

Zachry

et al. 2023

Sci Rep

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“…When compared with males, female MSNs display higher mEPSC frequency prepubertally, indicating an organizational nature of these sex differences as well [ 52 ]. Furthermore, in the adult NAcC, females exhibit higher AMPA/NMDA ratios [ 53 ]. Additionally, females have a larger readily releasable pool of glutamate, but display a lower release probability [ 53 ].…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, in the adult NAcC, females exhibit higher AMPA/NMDA ratios [ 53 ]. Additionally, females have a larger readily releasable pool of glutamate, but display a lower release probability [ 53 ].…”

Section: Introductionmentioning

confidence: 99%

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

Johnson,

Chapp,

Lind

et al. 2023

Biol Sex Differ

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Background The 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. Methods We 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. Results Although 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. Conclusions Taken 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.

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Effects of chronic insecticide exposure on neuronal network development in vitro in rat cortical cultures

van Melis,

Peerdeman,

González

et al. 2024

Arch Toxicol

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Developmental exposure to carbamates, organophosphates, and pyrethroids has been associated with impaired neurodevelopmental outcomes. Sex-specific differences following chronic insecticide exposure are rather common in vivo. Therefore, we assessed the chronic effects of in vitro exposure to different carbamates (carbaryl, methomyl and aldicarb), organophosphates [chlorpyrifos (CPF), chlorpyrifos-oxon (CPO), and 3,5,6,trichloropyridinol (TCP)], and pyrethroids [permethrin, alpha-cypermethrin and 3-phenoxy benzoic acid (3-PBA)] on neuronal network development in sex-separated rat primary cortical cultures using micro-electrode array (MEA) recordings. Our results indicate that exposure for 1 week to carbaryl inhibited neurodevelopment in male cultures, while a hyperexcitation was observed in female cultures. Methomyl and aldicarb evoked a hyperexcitation after 2 weeks of exposure, which was more pronounced in female cultures. In contrast to acute MEA results, exposure to ≥ 10 µM CPF caused hyperexcitation in both sexes after 10 days. Interestingly, exposure to 10 µM CPO induced a clear hyperexcitation after 10 days of exposure in male but not female cultures. Exposure to 100 µM CPO strongly inhibited neuronal development. Exposure to the type I pyrethroid permethrin resulted in a hyperexcitation at 10 µM and a decrease in neuronal development at 100 µM. In comparison, exposure to ≥ 10 µM of the type II pyrethroid alpha-cypermethrin decreased neuronal development. In female but not in male cultures, exposure to 1 and 10 µM permethrin changed (network) burst patterns, with female cultures having shorter (network) bursts with fewer spikes per (network) burst. Together, these results show that MEA recordings are suitable for measuring sex-specific developmental neurotoxicity in vitro. Additionally, pyrethroid exposure induced effects on neuronal network development at human-relevant concentrations. Finally, chronic exposure has different effects on neuronal functioning compared to acute exposure, highlighting the value of both exposure paradigms.

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Sex differences in pre- and post-synaptic glutamate signaling in the nucleus accumbens core

Cited by 7 publications

References 103 publications

Nucleus accumbens core single cell ensembles bidirectionally respond to experienced versus observed aversive events

Nucleus accumbens core single cell ensembles bidirectionally respond to experienced versus observed aversive events

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

Effects of chronic insecticide exposure on neuronal network development in vitro in rat cortical cultures

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