scholarly journals Electrophysiological properties of medium spiny neurons in the nucleus accumbens core of prepubertal male and female Drd1a-tdTomato line 6 BAC transgenic mice

2018 ◽  
Vol 120 (4) ◽  
pp. 1712-1727 ◽  
Author(s):  
Jinyan Cao ◽  
David M. Dorris ◽  
John Meitzen
Keyword(s):  
Sex Differences ◽  
Nucleus Accumbens ◽  
Transgenic Mice ◽  
Brain Region ◽  
Reward Processing ◽  
Medium Spiny Neuron ◽  
Nucleus Accumbens Core ◽  
Male And Female ◽  
Electrophysiological Properties ◽  
Accumbens Core

The nucleus accumbens core (AcbC) is a striatal brain region essential for integrating motivated behavior and reward processing with premotor function. In humans and rodents, research has identified sex differences and sex steroid hormone sensitivity in AcbC-mediated behaviors, in disorders, and in rats in the electrophysiological properties of the AcbC output neuron type, the medium spiny neuron (MSN). It is unknown whether the sex differences detected in MSN electrophysiological properties extend to mice. Furthermore, MSNs come in distinct subtypes with subtle differences in electrophysiological properties, and it is unknown whether MSN subtype-specific electrophysiology varies by sex. To address these questions, we used male and female Drd1a-tdTomato line 6 bacterial artificial chromosome transgenic mice. We made acute brain slices of the AcbC, and performed whole cell patch-clamp recordings across MSN subtypes to comprehensively assess AcbC MSN subtype electrophysiological properties. We found that ( 1 mice MSNs did not exhibit the sex differences detected in rat MSNs, and 2) electrophysiological properties differed between MSN subtypes in both sexes, including rheobase, resting membrane potential, action potential properties, intrinsic excitability, input resistance in both the linear and rectified ranges, and miniature excitatory postsynaptic current properties. These findings significantly extend previous studies of MSN subtypes performed in males or animals of undetermined sex and indicate that the influence of sex upon AcbC MSN properties varies between rodent species. NEW & NOTEWORTHY This research provides the most comprehensive assessment of medium spiny neuron subtype electrophysiological properties to date in a critical brain region, the nucleus accumbens core. It additionally represents the first evaluation of whether mouse medium spiny neuron subtype electrophysiological properties differ by sex.

scholarly journals Nucleus accumbens core medium spiny neuron electrophysiological properties and partner preference behavior in the adult male prairie vole, Microtus ochrogaster

2018 ◽  
Vol 119 (4) ◽  
pp. 1576-1588 ◽  
Author(s):  
Jaime A. Willett ◽  
Ashlyn G. Johnson ◽  
Andrea R. Vogel ◽  
Heather B. Patisaul ◽  
Lisa A. McGraw ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Social Behavior ◽  
Adult Male ◽  
Prairie Vole ◽  
Medium Spiny Neuron ◽  
Partner Preference ◽  
Nucleus Accumbens Core ◽  
Electrophysiological Properties ◽  
Preference Behavior ◽  
Accumbens Core

Medium spiny neurons (MSNs) in the nucleus accumbens have long been implicated in the neurobiological mechanisms that underlie numerous social and motivated behaviors as studied in rodents such as rats. Recently, the prairie vole has emerged as an important model animal for studying social behaviors, particularly regarding monogamy because of its ability to form pair bonds. However, to our knowledge, no study has assessed intrinsic vole MSN electrophysiological properties or tested how these properties vary with the strength of the pair bond between partnered voles. Here we performed whole cell patch-clamp recordings of MSNs in acute brain slices of the nucleus accumbens core (NAc) of adult male voles exhibiting strong and weak preferences for their respective partnered females. We first document vole MSN electrophysiological properties and provide comparison to rat MSNs. Vole MSNs demonstrated many canonical electrophysiological attributes shared across species but exhibited notable differences in excitability compared with rat MSNs. Second, we assessed male vole partner preference behavior and tested whether MSN electrophysiological properties varied with partner preference strength. Male vole partner preference showed extensive variability. We found that decreases in miniature excitatory postsynaptic current amplitude and the slope of the evoked action potential firing rate to depolarizing current injection weakly associated with increased preference for the partnered female. This suggests that excitatory synaptic strength and neuronal excitability may be decreased in MSNs in males exhibiting stronger preference for a partnered female. Overall, these data provide extensive documentation of MSN electrophysiological characteristics and their relationship to social behavior in the prairie vole. NEW & NOTEWORTHY This research represents the first assessment of prairie vole nucleus accumbens core medium spiny neuron intrinsic electrophysiological properties and probes the relationship between cellular excitability and social behavior.

scholarly journals Estrous cycle-induced sex differences in medium spiny neuron excitatory synaptic transmission and intrinsic excitability in adult rat nucleus accumbens core

2018 ◽  
Vol 120 (3) ◽  
pp. 1356-1373 ◽  
Author(s):  
Stephanie B. Proaño ◽  
Hannah J. Morris ◽  
Lindsey M. Kunz ◽  
David M. Dorris ◽  
John Meitzen
Keyword(s):  
Sex Differences ◽  
Nucleus Accumbens ◽  
Estrous Cycle ◽  
Adult Female ◽  
Medium Spiny Neuron ◽  
Nucleus Accumbens Core ◽  
Female Hormone ◽  
Electrophysiological Properties ◽  
Adult Rat ◽  
Males And Females

Naturally occurring hormone cycles in adult female humans and rodents create a dynamic neuroendocrine environment. These cycles include the menstrual cycle in humans and its counterpart in rodents, the estrous cycle. These hormone fluctuations induce sex differences in the phenotypes of many behaviors, including those related to motivation, and associated disorders such as depression and addiction. This suggests that the neural substrate instrumental for these behaviors, including the nucleus accumbens core (AcbC), likewise differs between estrous cycle phases. It is unknown whether the electrophysiological properties of AcbC output neurons, medium spiny neurons (MSNs), change between estrous cycle phases. This is a critical knowledge gap given that MSN electrophysiological properties are instrumental for determining AcbC output to efferent targets. Here we test whether the intrinsic electrophysiological properties of adult rat AcbC MSNs differ across female estrous cycle phases and from males. We recorded MSNs with whole cell patch-clamp technique in two experiments, the first using gonad-intact adult males and females in differing phases of the estrous cycle and the second using gonadectomized males and females in which the estrous cycle was eliminated. MSN intrinsic electrophysiological and excitatory synaptic input properties robustly changed between female estrous cycle phases and males. Sex differences in MSN electrophysiology disappeared when the estrous cycle was eliminated. These novel findings indicate that AcbC MSN electrophysiological properties change across the estrous cycle, providing a new framework for understanding how biological sex and hormone cyclicity regulate motivated behaviors and other AcbC functions and disorders. NEW & NOTEWORTHY This research is the first demonstration that medium spiny neuron electrophysiological properties change across adult female hormone cycle phases in any striatal region. This influence of estrous cycle engenders sex differences in electrophysiological properties that are eliminated by gonadectomy. Broadly, these findings indicate that adult female hormone cycles are an important factor for neurophysiology.

The contribution of medium spiny neuron subtypes in the nucleus accumbens core to compulsive-like ethanol drinking

2021 ◽  
Vol 187 ◽  
pp. 108497 ◽  
Author(s):  
Elizabeth A. Sneddon ◽  
Kristen M. Schuh ◽  
John W. Frankel ◽  
Anna K. Radke
Keyword(s):  
Nucleus Accumbens ◽  
Medium Spiny Neuron ◽  
Nucleus Accumbens Core ◽  
Ethanol Drinking ◽  
Accumbens Core

scholarly journals Metformin in nucleus accumbens core reduces cue-induced cocaine seeking in male and female rats

2021 ◽  
Author(s):  
Amy Chan ◽  
Alexis Willard ◽  
Sarah Mulloy ◽  
Noor Ibrahim ◽  
Allegra Sciaccotta ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Female Rats ◽  
Therapeutic Effects ◽  
Self Administration ◽  
Nucleus Accumbens Core ◽  
Male And Female ◽  
Male And Female Rats ◽  
Cocaine Seeking ◽  
Ampk Activity ◽  
Accumbens Core

This study investigated the potential therapeutic effects of the FDA-approved drug metformin on cue-induced reinstatement of cocaine seeking. Metformin (dimethyl-biguanide) is a first-line treatment for type II diabetes that, among other mechanisms, is involved in the activation of adenosine monophosphate activated protein kinase (AMPK). Cocaine self-administration and extinction is associated with decreased levels of phosphorylated AMPK within the nucleus accumbens core (NAcore). Previously it was shown that increasing AMPK activity in the NAcore decreased cue-induced reinstatement of cocaine seeking. Decreasing AMPK activity produced the opposite effect. The goal of the present study was to determine if metformin in the NAcore reduces cue-induced cocaine seeking in adult male and female Sprague Dawley rats. Rats were trained to self-administer cocaine followed by extinction prior to cue-induced reinstatement trials. Metformin microinjected in the NAcore attenuated cue-induced reinstatement in male and female rats. Importantly, metformin's effects on cocaine seeking were not due to a general depression of spontaneous locomotor activity. In female rats, metformin's effects did generalize to a reduction in cue-induced reinstatement of sucrose seeking. These data support a potential role for metformin as a pharmacotherapy for cocaine use disorder, but warrant caution given the potential for metformin's effects to generalize to a natural reward in female rats.

scholarly journals Ceftriaxone and mGlu2/3 interactions in the nucleus accumbens core affect the reinstatement of cocaine-seeking in male and female rats

2020 ◽  
Vol 237 (7) ◽  
pp. 2007-2018 ◽  
Author(s):  
Carly N. Logan ◽  
Allison R. Bechard ◽  
Peter U. Hamor ◽  
Lizhen Wu ◽  
Marek Schwendt ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Female Rats ◽  
Nucleus Accumbens Core ◽  
Male And Female ◽  
Male And Female Rats ◽  
Cocaine Seeking ◽  
Core Affect ◽  
Accumbens Core

scholarly journals Estradiol rapidly modulates excitatory synapse properties in a sex- and region-specific manner in rat nucleus accumbens core and caudate-putamen

2019 ◽  
Vol 122 (3) ◽  
pp. 1213-1225 ◽  
Author(s):  
Amanda A. Krentzel ◽  
Lily R. Barrett ◽  
John Meitzen
Keyword(s):  
Sex Differences ◽  
Nucleus Accumbens ◽  
Excitatory Synapse ◽  
Medium Spiny Neurons ◽  
Nucleus Accumbens Core ◽  
Caudate Putamen ◽  
Spiny Neurons ◽  
Glutamatergic Signaling ◽  
Mepsc Frequency ◽  
Accumbens Core

Estradiol acutely facilitates sex differences in striatum-dependent behaviors. However, little is understood regarding the underlying mechanism. In striatal regions in adult rodents, estrogen receptors feature exclusively extranuclear expression, suggesting that estradiol rapidly modulates striatal neurons. We tested the hypothesis that estradiol rapidly modulates excitatory synapse properties onto medium spiny neurons (MSNs) of two striatal regions, the nucleus accumbens core and caudate-putamen in adult female and male rats. We predicted there would be sex-specific differences in pre- and postsynaptic locus and sensitivity. We further analyzed whether MSN intrinsic properties are predictive of estrogen sensitivity. Estradiol exhibited sex-specific acute effects in the nucleus accumbens core: miniature excitatory postsynaptic current (mEPSC) frequency robustly decreased in response to estradiol in female MSNs, and mEPSC amplitude moderately increased in response to estradiol in both male and female MSNs. This increase in mEPSC amplitude is associated with MSNs featuring increased intrinsic excitability. No MSN intrinsic electrical property associated with changes in mEPSC frequency. Estradiol did not acutely modulate mEPSC properties in the caudate-putamen of either sex. This is the first demonstration of acute estradiol action on MSN excitatory synapse function. This demonstration of sex and striatal region-specific acute estradiol neuromodulation revises our understanding of sex hormone action on striatal physiology and resulting behaviors. NEW & NOTEWORTHY This study is the first to demonstrate rapid estradiol neuromodulation of glutamatergic signaling on medium spiny neurons (MSNs), the major output neuron of the striatum. These findings emphasize that sex is a significant biological variable both in MSN sensitivity to estradiol and in pre- and postsynaptic mechanisms of glutamatergic signaling. MSNs in different regions exhibit diverse responses to estradiol. Sex- and region-specific estradiol-induced changes to excitatory signaling on MSNs explain sex differences partially underlying striatum-mediated behaviors and diseases.

scholarly journals Electrophysiological Properties of Medium Spiny Neuron Subtypes in the Caudate-Putamen of Prepubertal Male and Female Drd1a-tdTomato Line 6 BAC Transgenic Mice

eNeuro ◽  
2019 ◽  
Vol 6 (2) ◽  
pp. ENEURO.0016-19.2019 ◽  
Author(s):  
Jaime A. Willett ◽  
Jinyan Cao ◽  
David M. Dorris ◽  
Ashlyn G. Johnson ◽  
Laura A. Ginnari ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Medium Spiny Neuron ◽  
Caudate Putamen ◽  
Male And Female ◽  
Electrophysiological Properties ◽  
Bac Transgenic Mice

scholarly journals Ceftriaxone and mGlu2/3 interactions in the nucleus accumbens core affect the reinstatement of cocaine-seeking in male and female rats

2020 ◽  
Author(s):  
Carly N. Logan ◽  
Allison R. Bechard ◽  
Peter U. Hamor ◽  
Lizhen Wu ◽  
Marek Schwendt ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Surface Expression ◽  
Receptor Expression ◽  
Female Rats ◽  
Beta Lactam ◽  
Nucleus Accumbens Core ◽  
Male And Female ◽  
Male And Female Rats ◽  
Cocaine Seeking ◽  
Accumbens Core

AbstractRationaleThe beta-lactam antibiotic ceftriaxone reliably attenuates the reinstatement of cocaine-seeking. While the restoration of nucleus accumbens core (NA core) GLT-1 expression is necessary for ceftriaxone to attenuate reinstatement, AAV-mediated GLT-1 overexpression is not sufficient to attenuate reinstatement and does not prevent glutamate efflux during reinstatement.AimsHere, we test the hypothesis that ceftriaxone attenuates reinstatement through interactions with glutamate autoreceptors mGlu2 and mGlu3 in the NA core.MethodsMale and female rats self-administered cocaine for 12 days followed by 2-3 weeks of extinction training. During the last 6-10 days of extinction, rats received ceftriaxone (200 mg/kg IP) or vehicle. In experiment 1, rats were killed, and NA core tissue was biotinylated for assessment of total and surface expression of mGlu2 and mGlu3 via western blotting. In experiment 2, we tested the hypothesis that mGlu2/3 signaling is necessary for ceftriaxone to attenuate cue- and cocaine-primed reinstatement by administering bilateral intra-NA core infusion of mGlu2/3 antagonist LY341495 or vehicle immediately prior to reinstatement testing.ResultsmGlu2 expression was reduced by cocaine and restored by ceftriaxone. There were no effects of cocaine or ceftriaxone on mGlu3 expression. We observed no effects of estrus on expression of either protein. The antagonism of mGlu2/3 in the NA core during both cue- and cocaine-primed reinstatement tests prevented ceftriaxone from attenuating reinstatement.ConclusionsThese results indicate that ceftriaxone’s effects depend on mGlu2/3 function and possibly mGlu2 receptor expression. Future work will test this hypothesis by manipulating mGlu2 expression in pathways that project to the NA core.

scholarly journals Differential and synergistic roles of 17β-estradiol and progesterone in modulating adult female rat nucleus accumbens core medium spiny neuron electrophysiology

2020 ◽  
Vol 123 (6) ◽  
pp. 2390-2405 ◽  
Author(s):  
Stephanie B. Proaño ◽  
Amanda A. Krentzel ◽  
John Meitzen
Keyword(s):  
Nucleus Accumbens ◽  
Estrous Cycle ◽  
Adult Female ◽  
Medium Spiny Neuron ◽  
Female Rat ◽  
Nucleus Accumbens Core ◽  
17Β Estradiol ◽  
Rat Nucleus Accumbens ◽  
Neuron Electrophysiology ◽  
Accumbens Core

This research indicates that estradiol and progesterone act both differentially and synergistically to modulate neuron physiology in the nucleus accumbens core. These actions by specific hormones provide key data indicating the endocrine mechanisms underlying how the estrous cycle modulates neuron physiology in this region. Overall, these data reinforce that hormones are an important influence on neural physiology.

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