Oxytocin enhances hippocampal spike transmission by modulating fast-spiking interneurons

Owen, Scott F.; Tuncdemir, Sebnem N.; Bader, Patrick L.; Tirko, Natasha N.; Fishell, Gord; Tsien, Richard W.

doi:10.1038/nature12330

Cited by 309 publications

(358 citation statements)

References 36 publications

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“…Indeed, OT has been shown to increase spike output [89][90][91] and facilitate synaptic long-term potentiation [92][93][94] and our data suggest an intrinsic mechanism that may underlie shifts in synaptic efficacy and excitatory/inhibitory balance found in brain regions where OT is critical for myriad social behaviors 67,74,90,95 . Intrinsic properties are shaped by ion channels.…”

Section: Discussionmentioning

confidence: 94%

Insular Cortex Mediates Approach and Avoidance Responses to Social Affective Stimuli

Rogers

Varela

Gribbons

et al. 2017

Preprint

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Social animals detect the affective states of others and utilize this information to orchestrate appropriate social interactions. Social affective behaviors include cooperation, reproductive acts and avoiding sick individuals. In a social affective behavioral test in which experimental adult male rats were given the choice to interact with either naive or stressed conspecifics, the experimental rats demonstrated both approach and avoidant behaviors towards the conspecific, depending upon the age of the conspecific; experimental adult rats approached the stressed juvenile but avoided the stressed adult. Optogenetic inhibition of the insular cortex, a region anatomically positioned to contribute to social cognition, disrupted these behaviors. Receptors for the social nonapeptide oxytocin (OT) are found in high density within the insular cortex and here oxytocin increased intrinsic excitability and synaptic efficacy in acute insular cortex slices. Blockade of oxytocin receptors (OTRs) in the insula eliminated the effect of conspecific stress on approach behavior, while insular administration of OT recapitulated the behaviors typically observed in response to stressed conspecifics. Network analysis using Fos immunoreactivity identified functional connectivity between the insular cortex and the network of regions involved in social decision making. These results implicate insular cortex as a novel target of OT and suggest that insula is a key component in the circuit underlying age-dependent social responses to stressed conspecifics.Social animals, including humans, have an enormous repertoire of behavioral expressions that provide for the transmission of one's affective state to other members of the group 1-3 . Sensory and perceptive systems in the "social decision-making network" (SDMN) which consists of the social brain network 4 and the mesolimbic reward system 5 allow one to appraise these social stimuli and integrate them with past experiences, situational, and somatic factors to shape specific behavioral responses 6 . In addition to the SDMN, growing evidence implicates insular cortex in responding to socioemotional stimuli in humans. When tasked to identify the emotion of another from a facial expression, or to observe another suffer a painful stimulation, a reliable neural correlate is relative increase in the blood oxygen level dependent (BOLD) signal in the insular cortex 7,8 . Accordingly, emotion recognition and empathic deficits have been reported among individuals with insular cortex lesions [9][10][11][12] . Empathic processes are also disrupted in autism spectrum 1 Department of Psychology, Boston College, Chestnut Hill, MA 02467, USA 2 These authors made equal contributions to this work. *Corresponding Author: John P. Christianson, Department of Psychology, Boston College, 140 Commonwealth Avenue, Chestnut Hill, MA 02467 USA, Email: j.christianson@bc.edu, Phone: +1-617-552-3970.A note about the preprint. This manuscript was submitted to bioRxiv.org after multiple rounds of peer review. The manuscrip...

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Section: Discussionmentioning

confidence: 94%

Insular Cortex Mediates Approach and Avoidance Responses to Social Affective Stimuli

Rogers

Varela

Gribbons

et al. 2017

Preprint

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“…Our findings may be consistent with the recent discovery that OT administration can increase the activity of fast-spiking interneuron activity in the rodent hippocampus. This suppresses spontaneous pyramidal cell firing while simultaneously enhancing the fidelity of spike transmission, and it also sharpens spike timing (41). These two processes, one increasing activity and the other decreasing activity, effectively boost "signal-to-noise" in favor of certain stimuli and thereby serve to tune brain responses to that class of stimuli.…”

Section: Discussionmentioning

confidence: 99%

Oxytocin enhances brain function in children with autism

Gordon

Wyk

Bennett

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

284

220

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Following intranasal administration of oxytocin (OT), we measured, via functional MRI, changes in brain activity during judgments of socially (Eyes) and nonsocially (Vehicles) meaningful pictures in 17 children with high-functioning autism spectrum disorder (ASD). OT increased activity in the striatum, the middle frontal gyrus, the medial prefrontal cortex, the right orbitofrontal cortex, and the left superior temporal sulcus. In the striatum, nucleus accumbens, left posterior superior temporal sulcus, and left premotor cortex, OT increased activity during social judgments and decreased activity during nonsocial judgments. Changes in salivary OT concentrations from baseline to 30 min postadministration were positively associated with increased activity in the right amygdala and orbitofrontal cortex during social vs. nonsocial judgments. OT may thus selectively have an impact on salience and hedonic evaluations of socially meaningful stimuli in children with ASD, and thereby facilitate social attunement. These findings further the development of a neurophysiological systems-level understanding of mechanisms by which OT may enhance social functioning in children with ASD.A utism spectrum disorder (ASD) is a common, early-onset neurodevelopmental disorder characterized by devastating difficulties in social interaction, communication, and repetitive or restricted interests and behaviors. ASD displays great phenotypic heterogeneity and etiological diversity, but its original characterization, social dysfunction, has been its hallmark and unifying feature (1). There is no established pharmacological treatment for social impairment in ASD.When given acutely, intranasal oxytocin (OT) leads to enhanced processing of social stimuli in typically developing adults, as evidenced by increased eye contact, in-group trust, and emotion recognition from facial expressions (2-4). At the level of neural systems, intranasal OT heightens activity in a set of neuroanatomical structures involved in processing socially meaningful stimuli in typically developing adults (5, 6). Recently, the first brain imaging study in adults with ASD examined the effects of OT administration and identified increased activation in the right amygdala during social information processing (7).Behavioral studies demonstrate that in children and adults with ASD, a single administration of intranasal OT leads to increased willingness to interact socially (8), better comprehension of affective speech (9), reduced repetitive behaviors (10), increased understanding of others' mental states (11), and improved social cognition (12). Despite cautionary calls regarding the use of OT in children to treat ASD before understanding the neural mechanisms underlying OT's complex impact on behavior (13), there have been no studies on the effects of OT administration on brain activity in children. Furthermore, although there are several large-scale clinical trials currently underway (www. clinicaltrials.gov) to examine the effects of chronically administered OT in ASD, the e...

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“…In rodents, endogenous and exogenous oxytocin binds in brain regions associated with mood, arousal, and reward (Gimpl and Fahrenholz, 2001) and also increases levels of dopamine, serotonin, and norepinephrine (Shahrokh et al, 2010;Vincent and Etgen, 1993;Yoshida et al, 2009). However, in contrast to MDMA, oxytocin modulates release of monoamines via activation of oxytocin receptors (Gimpl and Fahrenholz, 2001), and may have relatively specific and focused neuromodulatory effects on improved information processing in the brain (Owen et al, 2013). Of course, the extent to which intranasal oxytocin acts on specific brain circuits and facilitates neurotransmitter release in humans has yet to be determined.…”

Section: Discussionmentioning

confidence: 99%

Effects of MDMA and Intranasal Oxytocin on Social and Emotional Processing

Kirkpatrick

Lee

Wardle

et al. 2014

Neuropsychopharmacol

117

129

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MDMA (±3,4-methylenedioxymethamphetamine, 'ecstasy') is used recreationally, reportedly because it increases feelings of empathy, sociability, and interpersonal closeness. One line of evidence suggests that MDMA produces these effects by releasing oxytocin, a peptide involved in social bonding. In the current study, we investigated the acute effects of MDMA and oxytocin on social and emotional processing in healthy human volunteers. MDMA users (N ¼ 65) participated in a 4-session, within-between-subjects study in which they received oral MDMA (0.75, 1.5 mg/kg), intranasal oxytocin (20 or 40 IU), or placebo under double-blind conditions. The primary outcomes included measures of emotion recognition and sociability (desire to be with others). Cardiovascular and subjective effects were also assessed. As expected, MDMA dose-dependently increased heart rate and blood pressure and feelings of euphoria (eg, 'High' and 'Like Drug'). On measures of social function, MDMA impaired recognition of angry and fearful facial expressions, and the larger dose (1.5 mg/kg) increased desire to be with others, compared with placebo. Oxytocin produced small but significant increases in feelings of sociability and enhanced recognition of sad facial expressions. Additionally, responses to oxytocin were related to responses to MDMA with subjects on two subjective measures of sociability. Thus, MDMA increased euphoria and feelings of sociability, perhaps by reducing sensitivity to subtle signs of negative emotions in others. The present findings provide only limited support for the idea that oxytocin produces the prosocial effects of MDMA.

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Oxytocin enhances hippocampal spike transmission by modulating fast-spiking interneurons

Cited by 309 publications

References 36 publications

Insular Cortex Mediates Approach and Avoidance Responses to Social Affective Stimuli

Insular Cortex Mediates Approach and Avoidance Responses to Social Affective Stimuli

Oxytocin enhances brain function in children with autism

Effects of MDMA and Intranasal Oxytocin on Social and Emotional Processing

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