Dopamine modulates an mGluR5-mediated depolarization underlying prefrontal persistent activity

Sidiropoulou, Kyriaki; Lu, Fang; Fowler, Melissa; Xiao, Rui; Phillips, Christopher W.; Ozkan, Emin D.; Zhu, Michael X.; White, Francis J.; Cooper, Donald

doi:10.1038/nn.2245

Cited by 122 publications

(113 citation statements)

References 51 publications

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“…Standard artificial cerebrospinal fluid (aCSF) and recording solutions were used 108 . aCSF recording composition was (in mM) NaCl 125, KCl 2.5, NaHCO3 25, NaH2PO4 1.25, MgCl2 1, CaCl2 2 and Glucose 10; pH = 7.40; 310 mOsm; aCSF cutting solution was: Sucrose 75, NaCl 87, KCl 2.5, NaHCO3 25, NaH2PO4 1.25, MgCl2 7, CaCl2 0.5, Glucose 25 and Kynureinic acid 1; pH=7.40, 312 mOsm.…”

Section: Insular Cortex Cannula Placement and Microinjectionmentioning

confidence: 99%

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: Insular Cortex Cannula Placement and Microinjectionmentioning

confidence: 99%

Insular Cortex Mediates Approach and Avoidance Responses to Social Affective Stimuli

Rogers

Varela

Gribbons

et al. 2017

Preprint

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“…1). e di erences are a re ection of changes in the biophysical properties of the neurons 4 .We developed a simple ball and stick model and tted the data to elucidate the underlying conductances. Fig 2. EPSPs are functionally enhanced in escapable conditions compared to inescapable.…”

Section: Resultsmentioning

confidence: 99%

Control over stress induces plasticity of individual prefrontal cortical neurons: A conductance-based neural simulation

Varela¹,

Wang²,

Varnell³

et al. 2011

Nature Precedings

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Behavioral control over stressful stimuli induces resilience to future conditions when control is lacking. The medial prefrontal cortex(mPFC) is a critically important brain region required for plasticity of stress resilience. We found that control over stress induces plasticity of the intrinsic voltage-gated conductances of pyramidal neurons in the PFC. To gain insight into the underlying biophysical mechanisms of this plasticity we used the conductancebased neural simulation software tool, NEURON, to model the increase in membrane excitability associated with passive and active data traces from prototypical pyramidal neurons in neurons in rats with control over tail shock stress and those lacking control. The results indicate that the plasticity of membrane excitability associated with control over stress can be attributed to an increase in Na + and Ca 2+ T-type conductances and an increase in the leak conductance. Using simulated dendritic synaptic inputs we observed an increase in excitatory postsynaptic electrophysiological mechanistic studies in animal models of resilience and vulnerability to stress.Traumatic and stressful life events a ect individuals di erently depending on the degree of control they have over the stressors. An individual's sense of actual or perceived control over stressors is regarded as a potent coping mechanism that can boost resilience to a number of psychiatric conditions like anxiety, depression and posttraumatic stress disorder (PTSD). In rodent models, behavioral control over a stressor like mild electric tail shock prevents the physiological and learning de cits resulting from lack of control 1,2 . It has been demonstrated that the underlying mechanism of this type of control-mediated resilience requires lasting changes in neurotransmission in the medial prefrontal cortex (mPFC) 3 .We have recent unpublished data from electrophysiological recordings in brain slices of rats allowed to escape tail shock stress that shows pyramidal neuronal plasticity in the deep layers of the pre-limbic subregion of the mPFC. Compared to pyramidal neurons obtained from rats that lack control over shock or home caged, no-shock group the rats that are allowed to learn to escape undergo plasticity in their pyramidal neurons that increases their action potential output. As a group, rats with control have pyramidal neurons that exhibit a faster membrane time constant (TC), larger action potential (AP) amplitude, faster AP rise rate and a larger post-spike a er-depolarization (ADP).Because of the dynamical voltage, time and morphological interactions involved in the integration of excitatory and inhibitory input to pyramidal neurons we utilized a simpli ed conductance-based modeling approach to determine which critical ion channels could be modi ed to produce the physiological ndings we observed. To accomplish this we utilized the neural simulation tool NEURON to examine the relationships between various conductances to t the measure physiological data, and determine the conductance changes between th...

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“…Second, D1 receptors also act through PKA and mGlu receptors to modulate channels that contribute to a cell autonomous mechanism of persistent firing (Fig. 4B, Onn and Wang 2005;Witkowski et al 2008;Sidiropoulou et al 2009). In both cases presynaptic D1 receptors may enhance spontaneous release of glutamate, which then acts on postsynaptic NMDA or mGlu receptors.…”

Section: Presynaptic Receptors Spontaneous Release and Persistent Fmentioning

confidence: 99%

Possible contributions of a novel form of synaptic plasticity inAplysiato reward, memory, and their dysfunctions in mammalian brain

Hawkins

2013

Learn. Mem.

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Recent studies in Aplysia have identified a new variation of synaptic plasticity in which modulatory transmitters enhance spontaneous release of glutamate, which then acts on postsynaptic receptors to recruit mechanisms of intermediate-and long-term plasticity. In this review I suggest the hypothesis that similar plasticity occurs in mammals, where it may contribute to reward, memory, and their dysfunctions in several psychiatric disorders. In Aplysia, spontaneous release is enhanced by activation of presynaptic serotonin receptors, but presynaptic D1 dopamine receptors or nicotinic acetylcholine receptors could play a similar role in mammals. Those receptors enhance spontaneous release of glutamate in hippocampus, entorhinal cortex, prefrontal cortex, ventral tegmental area, and nucleus accumbens. In all of those brain areas, glutamate can activate postsynaptic receptors to elevate Ca 2+ and engage mechanisms of early-phase long-term potentiation (LTP), including AMPA receptor insertion, and of late-phase LTP, including protein synthesis and growth. Thus, presynaptic receptors and spontaneous release may contribute to postsynaptic mechanisms of plasticity in brain regions involved in reward and memory, and could play roles in disorders that affect plasticity in those regions, including addiction, Alzheimer's disease, schizophrenia, and attention deficit hyperactivity disorder (ADHD).

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Dopamine modulates an mGluR5-mediated depolarization underlying prefrontal persistent activity

Cited by 122 publications

References 51 publications

Insular Cortex Mediates Approach and Avoidance Responses to Social Affective Stimuli

Insular Cortex Mediates Approach and Avoidance Responses to Social Affective Stimuli

Control over stress induces plasticity of individual prefrontal cortical neurons: A conductance-based neural simulation

Possible contributions of a novel form of synaptic plasticity inAplysiato reward, memory, and their dysfunctions in mammalian brain

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