Cytoarchitectural impairments in the medium spiny neurons of the Nucleus Accumbens core of hyperactive juvenile rats

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.

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Erbb4 Deletion from Medium Spiny Neurons of the Nucleus Accumbens Core Induces Schizophrenia-Like Behaviors via Elevated GABAA Receptor α1 Subunit Expression

Journal of Neuroscience ◽

10.1523/jneurosci.3948-16.2017 ◽

2017 ◽

Vol 37 (31) ◽

pp. 7450-7464 ◽

Cited By ~ 7

Author(s):

Hong-Yan Geng ◽

Jing Zhang ◽

Jian-Ming Yang ◽

Yue Li ◽

Ning Wang ◽

...

Keyword(s):

Nucleus Accumbens ◽

Gabaa Receptor ◽

Medium Spiny Neurons ◽

Nucleus Accumbens Core ◽

Spiny Neurons ◽

Subunit Expression ◽

Α1 Subunit ◽

Accumbens Core

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Eating “junk food” has opposite effects on intrinsic excitability of nucleus accumbens core neurons in obesity-susceptible versus -resistant rats

Journal of Neurophysiology ◽

10.1152/jn.00361.2019 ◽

2019 ◽

Vol 122 (3) ◽

pp. 1264-1273 ◽

Cited By ~ 6

Author(s):

Max F. Oginsky ◽

Carrie R. Ferrario

Keyword(s):

Nucleus Accumbens ◽

Potassium Current ◽

Incentive Motivation ◽

Intrinsic Excitability ◽

Medium Spiny Neurons ◽

Junk Food ◽

Nucleus Accumbens Core ◽

Initial Finding ◽

Spiny Neurons ◽

Fast Transient

The nucleus accumbens (NAc) plays critical roles in motivated behaviors, including food seeking and feeding. Differences in NAc function contribute to overeating that drives obesity, but the underlying mechanisms are poorly understood. In addition, there is a fair degree of variation in individual susceptibility versus resistance to obesity that is due in part to differences in NAc function. For example, using selectively bred obesity-prone and obesity-resistant rats, we have found that excitability of medium spiny neurons (MSNs) within the NAc core is enhanced in obesity-prone versus -resistant populations, before any diet manipulation. However, it is unknown whether consumption of sugary, fatty “junk food” alters MSN excitability. Here whole cell patch-clamp recordings were conducted to examine MSN intrinsic excitability in adult male obesity-prone and obesity-resistant rats with and without exposure to a sugary, fatty junk food diet. We replicated our initial finding that basal excitability is enhanced in obesity-prone versus obesity-resistant rats and determined that this is due to a lower fast transient potassium current ( IA) in prone versus resistant groups. In addition, the junk food diet had opposite effects on excitability in obesity-prone versus obesity-resistant rats. Specifically, junk food enhanced excitability in MSNs of obesity-resistant rats; this was mediated by a reduction in IA. In contrast, junk food reduced excitability in MSNs from obesity-prone rats; this was mediated by an increase in inward-rectifying potassium current. Thus individual differences in obesity susceptibility influence both basal excitability and how MSN excitability adapts to junk food consumption. NEW & NOTEWORTHY Medium spiny neurons (MSNs) in the nucleus accumbens of obesity-prone rats are hyperexcitable compared with MSNs from obesity-resistant rats. We found that 10 days of “junk food” exposure reduces MSN excitability in obesity-prone rats by increasing inward-rectifying potassium current and increases MSN excitability in obesity-resistant rats by decreasing fast transient potassium current. These data show that there are basal and junk food diet-induced differences in MSN excitability in obesity-prone and obesity-resistant individuals; this may contribute to previously observed differences in incentive motivation.

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Faculty Opinions recommendation of Insular cortex projections to nucleus accumbens core mediate social approach to stressed juvenile rats.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.736727317.793567253 ◽

2019 ◽

Author(s):

Yavin Shaham

Keyword(s):

Nucleus Accumbens ◽

Insular Cortex ◽

Nucleus Accumbens Core ◽

Social Approach ◽

Juvenile Rats ◽

Accumbens Core

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Insular Cortex Projections to Nucleus Accumbens Core Mediate Social Approach to Stressed Juvenile Rats

Journal of Neuroscience ◽

10.1523/jneurosci.0316-19.2019 ◽

2019 ◽

Vol 39 (44) ◽

pp. 8717-8729 ◽

Cited By ~ 6

Author(s):

Morgan M. Rogers-Carter ◽

Anthony Djerdjaj ◽

K. Bates Gribbons ◽

Juan A. Varela ◽

John P. Christianson

Keyword(s):

Nucleus Accumbens ◽

Insular Cortex ◽

Nucleus Accumbens Core ◽

Social Approach ◽

Juvenile Rats ◽

Accumbens Core

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Eating junk-food has opposite effects on intrinsic excitability of nucleus accumbens core medium spiny neurons in obesity-susceptible vs. -resistant rats

10.1101/658971 ◽

2019 ◽

Author(s):

Max F. Oginsky ◽

Carrie R. Ferrario

Keyword(s):

Nucleus Accumbens ◽

Intrinsic Excitability ◽

Medium Spiny Neurons ◽

Junk Food ◽

Nucleus Accumbens Core ◽

Initial Finding ◽

Spiny Neurons ◽

Whole Cell Patch Clamp ◽

Underlying Mechanisms ◽

Food Seeking

AbstractThe nucleus accumbens (NAc) plays critical roles in motivated behaviors, including food-seeking and feeding. Differences in NAc function contribute to over-eating that drives obesity, but the underlying mechanisms are poorly understood. In addition, there is a fair degree of variation in individual susceptibility vs. resistance to obesity that is due in part to differences in NAc function. For example, using selectively bred obesity-prone and obesity-resistant rats, we have found that excitability of medium spiny neurons within the NAc core is enhanced in obesity-prone vs. resistant populations, prior to any diet manipulation. However, it is unknown whether consumption of sugary, fatty junk-food alters MSN excitability. Here, whole-cell patch clamp recordings were conducted to examine MSN intrinsic excitability in adult male obesity-prone and obesity-resistant rats with and without exposure to a sugary, fatty junk-food diet. We replicated our initial finding that basal excitability is enhanced in obesity-prone vs. obesity-resistant rats and determined that this is due to a lower IA in prone vs. resistant groups. In addition, the junk-food diet had opposite effects on excitability in obesity-prone vs. obesity-resistant rats. Specifically, junk-food enhanced excitability in MSNs of obesity-resistant rats; this was mediated by a reduction in IA. In contrast, junk-food reduced excitability in MSNs from obesity-prone rats; this was mediated by an increase in IKIR. Thus, individual differences in obesity-susceptibility influence both basal excitability and how MSN excitability adapts to junk-food consumption.

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