Functional organization of the dorsal raphe efferent system with special consideration of nitrergic cell groups

Vasudeva, Rani K.; Lin, Rick C.S.; Simpson, Kate; Waterhouse, Barry D.

doi:10.1016/j.jchemneu.2011.05.008

Cited by 72 publications

(63 citation statements)

References 148 publications

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“…It is well known that neuromodulator circuits supporting serotonin, dopamine, and norepinephrine are reciprocally interconnected (28,29). In particular, dopamine and serotonin can be coreleased upon stimulation (30).…”

Section: Resultsmentioning

confidence: 99%

Behavioral training reverses global cortical network dysfunction induced by perinatal antidepressant exposure

Zhou

Darling

et al. 2015

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

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Abnormal cortical circuitry and function as well as distortions in the modulatory neurological processes controlling cortical plasticity have been argued to underlie the origin of autism. Here, we chemically distorted those processes using an antidepressant drugexposure model to generate developmental neurological distortions like those characteristics expressed in autism, and then intensively trained altered young rodents to evaluate the potential for neuroplasticity-driven renormalization. We found that young rats that were injected s.c. with the antidepressant citalopram from postnatal d 1-10 displayed impaired neuronal repetition-rate following capacity in the primary auditory cortex (A1). With a focus on recovering grossly degraded auditory system processing in this model, we showed that targeted temporal processing deficits induced by early-life antidepressant exposure within the A1 were almost completely reversed through implementation of a simple behavioral training strategy (i.e., a modified go/no-go repetition-rate discrimination task). Degraded parvalbumin inhibitory GABAergic neurons and the fast inhibitory actions that they control were also renormalized by training. Importantly, antidepressant-induced degradation of serotonergic and dopaminergic neuromodulatory systems regulating cortical neuroplasticity was sharply reversed. These findings bear important implications for neuroplasticitybased therapeutics in autistic patients.autism | behavioral training | cortical network | antidepressant exposure | recovery of function R ecently, extensive efforts have been made to understand better the etiology of pervasive developmental disorders (PDDs), such as autism spectrum disorders (ASDs), with an ultimate goal of identifying preventive and more effective treatment strategies. At present, a general consensus from both human and animal studies is that a variety of genetic and environmental factors play an integrated role in the establishment of neurobehavioral abnormalities marking these disorders (1-5). Given the complexity of its origins and of the expressions of neurological abnormalities in ASD, it has been generally concluded that no single drug or therapy can be expected to provide effective treatment for the core and associated symptoms of ASDs (6-9).Interestingly, early behavioral intervention has been associated with significant improvements in intelligence quotient, language acquisition, and adaptive behavior (10). Furthermore, positive outcomes of individuals with an unequivocal history of moderate-severe ASD (11) provide hope that the strong behavioral deficits expressed in the disorder might, on some corrective neurobehavioral path, be reversible. What is that path? A critical question to answer is whether and to what extent the cortical network dysfunction and the subcortical machinery that regulates it, repeatedly described as distorted in humans with autism and in animal models of autism (12-15), can be reversed, either through drug treatment or via behavioral approaches.Cortical circuit mi...

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Section: Resultsmentioning

confidence: 99%

Behavioral training reverses global cortical network dysfunction induced by perinatal antidepressant exposure

Zhou

Darling

et al. 2015

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

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“…NOS neurons that project to the DRN include many regions involved in the stress response. Specifically, the paraventricular nucleus of the hypothalamus projects to both ventromedial and lateral wing regions [2]. The activation of thinner fibers in the lateral wings began at 1 hour of restraint and continued through 3 hours of restraint, which suggest that signaling from other regions occurs before increased NOS activation from DRN neurons (Figs 3, 4, 6B and 7B).…”

Section: Discussionmentioning

confidence: 90%

“…Similar to serotonergic neurons, neuronal nitric oxide synthase (NOS) neurons manifest in a unique topographical distribution and co-localization pattern across the DRN [2]. Most of the neurons in the dorsomedial and ventromedial DRN, collectively known as the midline, display both NOS and tryptophan hydroxylase (TPH), but neurons in the caudal lateral wing (CLW) display either NOS or TPH exclusively [2,3]. Interestingly, more than 75% of the neurons in the CLW that contain NOS were also positive for inhibitory 5-HT 1A receptors, suggesting that those neurons are regulated by 5-HT [1,3,4].…”

Section: Introductionmentioning

confidence: 99%

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0075 Nitrergic Neurons of the Dorsal Raphe Nucleus Encode Information About Stress Duration

Nichols-Obande

Anderson

Bush

et al. 2018

Sleep

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Nitrergic neurons of the dorsal raphe nucleus (DRN) may play a role in physiological stress responses. The caudal lateral wings (CLW) are unique compared to other rostral-caudal DRN sub-regions because they contain distinct nitric oxide (NO) synthase (NOS) populations that are independent of tryptophan hydroxylase (TPH). NOS neurons in the CLW are also highly activated during acute restraint stress. However, the effects of acute stress duration on NOS activation in the CLW are unclear. Here NADPH-d, an index of NOS activity, is used to show that sub-regions of the DRN have differential NOS activation in response to 6 hours of restraint stress in rats. We report increased NOS activity through 6 hours of restraint in the caudal lateral wings and ventromedial sub-regions. These data suggest that, NOS neurons may play a dynamic role in the response to stress duration.

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“…180−183 Furthermore, distinct, reproducible patterns of serotonin neuron activation within the raphe nuclei can be seen in response to specific external stimuli, suggesting that anatomical topography underlies functional topography. 182,184 Additionally, microdialysis studies examining extracellular serotonin levels after the application of various stressors have supported the idea of defined network patterns of serotonin neurons such that stressinduced changes in serotonin levels are stressor-and region specific. 185 These observations suggest that feedback inhibitory pathways might work to control serotonin-network activity.…”

Section: −142mentioning

confidence: 99%

Rethinking 5-HT_1A Receptors: Emerging Modes of Inhibitory Feedback of Relevance to Emotion-Related Behavior

Altieri¹,

Garcia-García

Leonardo

et al. 2012

ACS Chem. Neurosci.

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The complexities of the involvement of the serotonin transmitter system in numerous biological processes and psychiatric disorders is, to a substantial degree, attributable to the large number of serotonin receptor families and subtypes that have been identified and characterized for over four decades. Of these, the 5-HT 1A receptor subtype, which was the first to be cloned and characterized, has received considerable attention based on its purported role in the etiology and treatment of mood and anxiety disorders. 5-HT 1A receptors function both at presynaptic (autoreceptor) and postsynaptic (heteroreceptor) sites. Recent research has implicated distinct roles for these two populations of receptors in mediating emotion-related behavior. New concepts as to how 5-HT 1A receptors function to control serotonergic tone throughout life were highlights of the proceedings of the 2012 Serotonin Club Meeting in Montpellier, France. Here, we review recent findings and current perspectives on functional aspects of 5-HT 1A auto-and heteroreceptors with particular regard to their involvement in altered anxiety and mood states.

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Functional organization of the dorsal raphe efferent system with special consideration of nitrergic cell groups

Cited by 72 publications

References 148 publications

Behavioral training reverses global cortical network dysfunction induced by perinatal antidepressant exposure

Behavioral training reverses global cortical network dysfunction induced by perinatal antidepressant exposure

0075 Nitrergic Neurons of the Dorsal Raphe Nucleus Encode Information About Stress Duration

Rethinking 5-HT_1A Receptors: Emerging Modes of Inhibitory Feedback of Relevance to Emotion-Related Behavior

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Functional organization of the dorsal raphe efferent system with special consideration of nitrergic cell groups

Cited by 72 publications

References 148 publications

Behavioral training reverses global cortical network dysfunction induced by perinatal antidepressant exposure

Behavioral training reverses global cortical network dysfunction induced by perinatal antidepressant exposure

0075 Nitrergic Neurons of the Dorsal Raphe Nucleus Encode Information About Stress Duration

Rethinking 5-HT1A Receptors: Emerging Modes of Inhibitory Feedback of Relevance to Emotion-Related Behavior

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Rethinking 5-HT_1A Receptors: Emerging Modes of Inhibitory Feedback of Relevance to Emotion-Related Behavior