Neural Circuit Interactions between the Dorsal Raphe Nucleus and the Lateral Hypothalamus: An Experimental and Computational Study

Jalewa, Jaishree; Joshi, Alok; McGinnity, T.M.; Prasad, Girijesh; Wong‐Lin, KongFatt; Hölscher, Christian

doi:10.1371/journal.pone.0088003

Cited by 33 publications

(44 citation statements)

References 90 publications

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“…334 A more complex relationship exists between serotonin in the DRN and orexin. 335 Both are implicated in the regulation of sleep and in the depressive disorders, though there is no direct study of the effects on feeding.…”

Section: Non-homeostatic Control Of Feeding and Activitymentioning

confidence: 99%

Interacting Neural Processes of Feeding, Hyperactivity, Stress, Reward, and the Utility of the Activity-Based Anorexia Model of Anorexia Nervosa

Ross

Mandelblat-Cerf

Verstegen

2016

Harv Rev Psychiatry

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Anorexia nervosa (AN) is a psychiatric illness with minimal effective treatments and a very high rate of mortality. Understanding the neurobiological underpinnings of the disease is imperative for improving outcomes and can be aided by the study of animal models. The activity-based anorexia rodent model (ABA) is the current best parallel for the study of AN. This review describes the basic neurobiology of feeding and hyperactivity seen in both ABA and AN, and compiles the research on the role that stress-response and reward pathways play in modulating the homeostatic drive to eat and to expend energy, which become dysfunctional in ABA and AN.

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Section: Non-homeostatic Control Of Feeding and Activitymentioning

confidence: 99%

Interacting Neural Processes of Feeding, Hyperactivity, Stress, Reward, and the Utility of the Activity-Based Anorexia Model of Anorexia Nervosa

Ross

Mandelblat-Cerf

Verstegen

2016

Harv Rev Psychiatry

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“…The LH has, however, been investigated in both non-food (25, 53, 54), and food (55) reinforcement, and projections to the PVN and DRN (56, 57) have been characterized. The production of NMU by these projections, and the observed downstream regulation of feeding and food reinforcement by NMU release, is consistent with the alterations of NMU mRNA in response to energy balance (15).…”

Section: Discussionmentioning

confidence: 99%

Regulation of motivation for food by neuromedin U in the paraventricular nucleus and the dorsal raphe nucleus

2016

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BACKGROUNDMotivation for high-fat food is thought to contribute to excess caloric intake in obese individuals. A novel regulator of motivation for food may be Neuromedin U (NMU), a highly-conserved neuropeptide which influences food intake. Although these effects of NMU have primarily been attributed to signaling in the paraventricular nucleus of the hypothalamus (PVN), NMU has also been found in other brain regions involved in both feeding behavior and motivation. We investigate the effects of NMU on motivation for food and food intake, and identify the brain regions mediating these effects.METHODSThe motivational state for a particular reinforcer (e.g., high-fat food) can be assessed using a progressive ratio schedule of reinforcement under which an increasing number of lever presses are required to obtain subsequent reinforcers. Here, we have employed a progressive ratio operant responding paradigm in combination with an assessment of cumulative food intake to evaluate the effects of NMU administration in rats, and identify the brain regions mediating these effects.RESULTSWe found that peripheral administration of NMU decreases operant responding for high-fat food in rats. Evaluation of Fos-like immunoreactivity in response to peripheral NMU indicated the PVN and dorsal raphe nucleus (DRN) as sites of action for NMU. NMU infusion into either region mimics the effects of peripheral NMU on food intake and operant responding for food. NMU-containing projections from the lateral hypothalamus (LH) to the PVN and DRN were identified as an endogenous source of NMU.CONCLUSIONSThese results identify the DRN as a site of action for NMU, demonstrate that the LH provides endogenous NMU to the PVN and DRN, and implicate NMU signaling in the PVN and DRN as a novel regulator of motivation for high-fat foods.

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“…If the source of the interaction came from GABAergic (or Glu) neurons, then for simplicity, we assumed an instantaneous inhibitory (or excitatory) current-based synaptic influence on the targeted neuronal populations (see Methods). This reflected the faster ionotropic receptorbased synaptic dynamics compared to metabotropic receptor-based neuromodulatory effects (Jalewa et al, 2014), while also reducing the number of free model parameters. Similarly, we also ignored the relatively faster neuronal membrane dynamics.…”

Section: Computational Modelling Of the Drn-vta Circuitmentioning

confidence: 99%

Degeneracy and stability in neural circuits of dopamine and serotonin neuromodulators: A theoretical consideration

Behera

Joshi

Wang

et al. 2020

Preprint

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Degenerate neural circuits perform the same function despite being structurally different. However, it is unclear whether neural circuits with interacting neuromodulator sources can themselves be degenerate while maintaining the same neuromodulator function. Here, we address this by computationally modelling the neural circuits of neuromodulators serotonin and dopamine, local glutamatergic and GABAergic interneurons, and their possible interactions, under reward/aversion-based conditioning tasks. We show that a single sparsely connected neural circuit model can recapitulate many separate experimental findings, but not all, suggesting multiple parallel circuits. Using simulations and dynamical systems analysis, we demonstrate that several different stable circuit architectures can produce the same observed network activity profile. Further, simulating dopamine (D2) receptor agonists in rewarding task can distinguish among sub-groups of these degenerate networks; a testable model prediction. Overall, this work suggests the plausibility of degeneracy within neuromodulator circuitry and has important implication for the stable and robust maintenance of neuromodulator functions.

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Neural Circuit Interactions between the Dorsal Raphe Nucleus and the Lateral Hypothalamus: An Experimental and Computational Study

Cited by 33 publications

References 90 publications

Interacting Neural Processes of Feeding, Hyperactivity, Stress, Reward, and the Utility of the Activity-Based Anorexia Model of Anorexia Nervosa

Interacting Neural Processes of Feeding, Hyperactivity, Stress, Reward, and the Utility of the Activity-Based Anorexia Model of Anorexia Nervosa

Regulation of motivation for food by neuromedin U in the paraventricular nucleus and the dorsal raphe nucleus

Degeneracy and stability in neural circuits of dopamine and serotonin neuromodulators: A theoretical consideration

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