The Role of Parvalbumin Interneuron GIRK Signaling in the Regulation of Affect and Cognition in Male and Female Mice

Pathological impairments in the regulation of affect (i.e., emotion) and flexible decision-making are commonly observed across numerous neuropsychiatric disorders and are thought to reflect dysfunction of cortical and subcortical circuits that arise in part from imbalances in excitation and inhibition within these structures. Disruptions in GABA transmission, in particular, that from parvalbumin-expressing interneurons (PVI), has been highlighted as a likely mechanism by which this imbalance arises, as they regulate excitation and synchronization of principle output neurons. G protein-gated inwardly rectifying potassium ion (GIRK/Kir3) channels are known to modulate excitability and output of pyramidal neurons in areas like the medial prefrontal cortex and hippocampus; however, the role GIRK plays in PVI excitability and behavior is unknown. Male and female mice lacking GIRK1 in PVI (Girk1flox/flox:PVcre) and expressing td-tomato in PVI (Girk1flox/flox:PVCre:PVtdtom) exhibited increased open arm time in the elevated plus-maze, while males showed an increase in immobile episodes during the forced swim test (FST). Loss of GIRK1 did not alter motivated behavior for an appetitive reward or impair overall performance in an operant-based attention set-shifting model of cognitive flexibility; however it did alter types of errors committed during the visual cue test. Unexpectedly, baseline sex differences were also identified in these tasks, with females exhibiting overall poorer performance compared to males and distinct types of errors, highlighting potential differences in task-related problem-solving. Interestingly, reductions in PVI GIRK signaling did not correspond to changes in membrane excitability but did increase action potential (AP) firing at higher current injections in PVI of males, but not females. This is the first investigation on the role that PVI GIRK-signaling has on membrane excitability, AP firing, and their role on affect and cognition together increasing the understanding of PVI cellular mechanisms and function.

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The role of parvalbumin interneuron GIRK signaling in regulation of affect and cognition in male and female mice

10.1101/2020.10.28.359067 ◽

2020 ◽

Author(s):

EM Anderson ◽

S Demis ◽

H D’Acquisto ◽

A Engelhardt ◽

M Hearing

Keyword(s):

Action Potential ◽

Pyramidal Neurons ◽

Forced Swim Test ◽

Membrane Excitability ◽

Cellular Mechanisms ◽

Action Potential Firing ◽

Male And Female ◽

Female Mice ◽

Potential Firing ◽

Affect And Cognition

ABSTRACTPathological impairments in the regulation of affect (i.e. emotion) and flexible decision-making are commonly observed across numerous neuropsychiatric disorders and are thought to reflect dysfunction of cortical and subcortical circuits that arise in part from imbalances in excitation and inhibition within these structures. Disruptions in GABA transmission, in particular that from parvalbumin-expressing interneurons (PVI), has been highlighted as a likely mechanism by which this imbalance arises, as they regulate excitation and synchronization of principle output neurons. G protein-gated inwardly rectifying potassium ion (GIRK/Kir3) channels are known to modulate excitability and output of pyramidal neurons in areas like the medial prefrontal cortex and hippocampus, however the role GIRK plays in PVI excitability and behavior is unknown. Male and female mice lacking GIRK1 in PVI (Girk1flox/flox:PVcre) and expressing td-tomato in PVI (Girk1flox/flox:PVCre:PVtdtom) exhibited increased open arm time in the elevated plus maze, while males showed an increase in immobile episodes during the forced swim test. Loss of GIRK1 did not alter motivated behavior for an appetitive reward or impair overall performance in an operant-based attention set-shifting model of cognitive flexibility, however it did alter types of errors committed during the visual cue test. Unexpectedly, baseline sex differences were also identified in these tasks, with females exhibiting overall poorer performance compared to males and distinct types of errors, highlighting potential differences in task-related problem solving. Interestingly, reductions in PVI GIRK signaling did not correspond to changes in membrane excitability but did increase action potential firing at higher current injections in PVI of males, but not females. This is the first investigation on the role that PVI GIRK-signaling has on membrane excitability, action potential firing, and their role on affect and cognition together increasing understanding of PVI cellular mechanisms and function.

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Sex-Specific Differences in Oxytocin Receptor Expression and Function for Parental Behavior

Gender and the Genome ◽

10.1089/gg.2017.0017 ◽

2017 ◽

Vol 1 (4) ◽

pp. 1-25 ◽

Cited By ~ 1

Author(s):

Mariela Mitre ◽

Thorsten M. Kranz ◽

Bianca J. Marlin ◽

Jennifer K. Schiavo ◽

Hediye Erdjument-Bromage ◽

...

Keyword(s):

Auditory Cortex ◽

Maternal Behavior ◽

Parental Behavior ◽

Oxytocin Receptor ◽

Receptor Expression ◽

Male And Female ◽

Female Mice ◽

Oxytocin Receptors ◽

Males And Females ◽

And Function

Parental care is among the most profound behavior expressed by humans and other animals. Despite intense interest in understanding the biological basis of parental behaviors, it remains unknown how much of parenting is encoded by the genome and which abilities instead are learned or can be refined by experience. One critical factor at the intersection between innate behaviors and experience-dependent learning is oxytocin, a neurohormone important for maternal physiology and neuroplasticity. Oxytocin acts throughout the body and brain to promote prosocial and maternal behaviors and modulates synaptic transmission to affect neural circuit dynamics. Recently we developed specific antibodies to mouse oxytocin receptors, found that oxytocin receptors are left lateralized in female auditory cortex, and examined how oxytocin enables maternal behavior by sensitizing the cortex to infant distress sounds. In this study we compare oxytocin receptor expression and function in male and female mice. Receptor expression is higher in adult female left auditory cortex than in right auditory cortex or males. Developmental profiles and mRNA expression were comparable between males and females. Behaviorally, male and female mice began expressing parental behavior similarly after cohousing with experienced females; however, oxytocin enhanced parental behavior onset in females but not males. This suggests that left lateralization of oxytocin receptor expression in females provides a mechanism for accelerating maternal behavior onset, although male mice can also effectively co-parent after experience with infants. The sex-specific pattern of oxytocin receptor expression might genetically predispose female cortex to respond to infant cues, which both males and females can also rapidly learn.

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Lentiviral Interleukin-10 Gene Therapy Preserves Fine Motor Circuitry and Function After a Cervical Spinal Cord Injury in Male and Female Mice

Neurotherapeutics ◽

10.1007/s13311-020-00946-y ◽

2020 ◽

Author(s):

Jessica Y. Chen ◽

Emily J. Fu ◽

Paras R. Patel ◽

Alexander J. Hostetler ◽

Hasan A. Sawan ◽

...

Keyword(s):

Spinal Cord ◽

Gene Therapy ◽

Spinal Cord Injury ◽

Cervical Spinal Cord ◽

Interleukin 10 ◽

Fine Motor ◽

Male And Female ◽

Female Mice ◽

Cord Injury ◽

And Function

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Optogenetic stimulation of infralimbic PFC reproduces ketamine’s rapid and sustained antidepressant actions

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1414728112 ◽

2015 ◽

Vol 112 (26) ◽

pp. 8106-8111 ◽

Cited By ~ 114

Author(s):

Manabu Fuchikami ◽

Alexandra Thomas ◽

Rongjian Liu ◽

Eric S. Wohleb ◽

Benjamin B. Land ◽

...

Keyword(s):

Prefrontal Cortex ◽

Neuronal Activity ◽

Pyramidal Neurons ◽

Rodent Models ◽

Cellular Mechanisms ◽

Optogenetic Stimulation ◽

Layer V ◽

And Function ◽

Stimulation Of ◽

Synaptic Responses

Ketamine produces rapid and sustained antidepressant actions in depressed patients, but the precise cellular mechanisms underlying these effects have not been identified. Here we determined if modulation of neuronal activity in the infralimbic prefrontal cortex (IL-PFC) underlies the antidepressant and anxiolytic actions of ketamine. We found that neuronal inactivation of the IL-PFC completely blocked the antidepressant and anxiolytic effects of systemic ketamine in rodent models and that ketamine microinfusion into IL-PFC reproduced these behavioral actions of systemic ketamine. We also found that optogenetic stimulation of the IL-PFC produced rapid and long-lasting antidepressant and anxiolytic effects and that these effects are associated with increased number and function of spine synapses of layer V pyramidal neurons. The results demonstrate that ketamine infusions or optogenetic stimulation of IL-PFC are sufficient to produce long-lasting antidepressant behavioral and synaptic responses similar to the effects of systemic ketamine administration.

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Growth analysis of the mouse adrenal gland from weaning to adulthood: time- and gender-dependent alterations of cell size and number in the cortical compartment

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00705.2006 ◽

2007 ◽

Vol 293 (1) ◽

pp. E139-E146 ◽

Cited By ~ 52

Author(s):

Max Bielohuby ◽

Nadja Herbach ◽

Rüdiger Wanke ◽

Christiane Maser-Gluth ◽

Felix Beuschlein ◽

...

Keyword(s):

Adrenal Gland ◽

Adrenal Glands ◽

Zona Glomerulosa ◽

Careful Consideration ◽

Zona Fasciculata ◽

Systematic Analysis ◽

Male And Female ◽

Female Mice ◽

And Gender ◽

And Function

The adrenal gland is of critical importance for a plethora of biological processes. We performed the first systematic analysis of adrenal gland growth using unbiased stereological methods in male and female mice from weaning to adulthood ( weeks 3, 5, 7, 9, and 11) at the organ, compartment, and cellular levels. Adrenal weights increased from week 3 to week 7 in male and female mice, remained at this level in females, but decreased by 25% between week 7 and week 9 in males. Female adrenal glands displayed a higher weight at any stage investigated. The volume of the zona fasciculata was consistently higher in female vs. male mice. In both genders, the number of zona fasciculata cells reached a maximum at the age of 7 wk and decreased significantly until week 9. Serum corticosterone concentrations decreased from 3 to 11 wk of age both in male and female mice. However, the estimated total amounts of corticosterone in the circulation were similar in 3- and 11-wk-old mice. Furthermore, total circulating corticosterone was higher in females than in males at an age of 5 and 11 wk. In the zona glomerulosa and in the X-zone, time- and gender-dependent growth effects were observed. In conclusion, our results demonstrate that growth and function of the adrenal glands are markedly influenced by gender and age. These factors require careful consideration in studies aiming at the functional dissection of genetic and environmental factors affecting adrenal growth and function.

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The Effects of SRT1720 Treatment on Endothelial Cells Derived from the Lung and Bone Marrow of Young and Aged, Male and Female Mice

International Journal of Molecular Sciences ◽

10.3390/ijms222011097 ◽

2021 ◽

Vol 22 (20) ◽

pp. 11097

Author(s):

Ushashi Chand Dadwal ◽

Fazal Ur Rehman Bhatti ◽

Olatundun Dupe Awosanya ◽

Caio de Andrade Staut ◽

Rohit U. Nagaraj ◽

...

Keyword(s):

Bone Marrow ◽

Endothelial Cells ◽

Bone Healing ◽

Sirtuin 1 ◽

Male And Female ◽

Angiogenic Potential ◽

Migration Rates ◽

Female Mice ◽

Age Related ◽

And Function

Angiogenesis is critical for successful fracture healing. Age-related alterations in endothelial cells (ECs) may cause impaired bone healing. Therefore, examining therapeutic treatments to improve angiogenesis in aging may enhance bone healing. Sirtuin 1 (SIRT1) is highly expressed in ECs and its activation is known to counteract aging. Here, we examined the effects of SRT1720 treatment (SIRT1 activator) on the growth and function of bone marrow and lung ECs (BMECs and LECs, respectively), derived from young (3-4 month) and old (20–24 month) mice. While aging did not alter EC proliferation, treatment with SRT1720 significantly increased proliferation of all LECs. However, SRT1720 only increased proliferation of old female BMECs. Vessel-like tube assays showed similar vessel-like structures between young and old LECs and BMECs from both male and female mice. SRT1720 significantly improved vessel-like structures in all LECs. No age, sex, or treatment differences were found in migration related parameters of LECs. In males, old BMECs had greater migration rates than young BMECs, whereas in females, old BMECs had lower migration rates than young BMECs. Collectively, our data suggest that treatment with SRT1720 appears to enhance the angiogenic potential of LECs irrespective of age or sex. However, its role in BMECs is sex- and age-dependent.

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