Rapid sensory integration in orexin neurons governs probability of future movements

Karnani, Mahesh; SchoÌˆne, C.; Bracey, Edward F.; González, Joaquín; Viskaitis, Paulius; Adamantidis, Antoine; Burdakov, Denis

doi:10.1101/620096

Cited by 2 publications

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References 43 publications

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“…Here we used a Go/NoGo task to evaluate performance and motoric impulsivity behavior in mice and tested whether arousal driven by the neuropeptide Hcrt followed the Yerkes-Dodson Law. We show that hyperarousal induced by optogenetic stimulation of Hcrt neurons at frequencies consistent with their phasic activity profile 31,32 also decreases attention performance.…”

Section: Discussionmentioning

confidence: 73%

Optogenetic and pharmacological interventions link hypocretin neurons to impulsivity in mice

et al. 2023

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Neurons in the lateral hypothalamus expressing the neuropeptide Hypocretin, also known as orexin, are known critical modulators of arousal stability. However, their role in the different components of the arousal construct such as attention and decision making is poorly understood. Here we study Hypocretin neuronal circuit dynamics during stop action impulsivity in a Go/NoGo task in mice. We show that Hypocretin neuronal activity correlates with anticipation of reward. We then assessed the causal role of Hypocretin neuronal activity using optogenetics in a Go/NoGo task. We show that stimulation of Hypocretin neurons during the cue period dramatically increases the number of premature responses. These effects are mimicked by amphetamine, reduced by atomoxetine, a norepinephrine uptake inhibitor, and blocked by a Hypocretin receptor 1 selective antagonist. We conclude that Hypocretin neurons have a key role in the integration of salient stimuli during wakefulness to produce appropriate and timely responses to rewarding and aversive cues.

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Section: Discussionmentioning

confidence: 73%

Optogenetic and pharmacological interventions link hypocretin neurons to impulsivity in mice

et al. 2023

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“…In vivo , the changes in LH orexin neuron firing rate can occur both rapidly and slowly, and alter behaviors either quickly (sub-second) or slowly (minutes to hours) ( Adamantidis et al, 2007 ; Karnani et al, 2019 ). The slow changes in activity of orexin neurons are thought to represent changes in the internal body state.…”

Section: Information Represented By Lh Neuropeptidergic Neuronsmentioning

confidence: 99%

Neuropeptides as Primary Mediators of Brain Circuit Connectivity

Guillaumin

Burdakov

2021

Front. Neurosci.

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Across sleep and wakefulness, brain function requires inter-neuronal interactions lasting beyond seconds. Yet, most studies of neural circuit connectivity focus on millisecond-scale interactions mediated by the classic fast transmitters, GABA and glutamate. In contrast, neural circuit roles of the largest transmitter family in the brain–the slow-acting peptide transmitters–remain relatively overlooked, or described as “modulatory.” Neuropeptides may efficiently implement sustained neural circuit connectivity, since they are not rapidly removed from the extracellular space, and their prolonged action does not require continuous presynaptic firing. From this perspective, we review actions of evolutionarily-conserved neuropeptides made by brain-wide-projecting hypothalamic neurons, focusing on lateral hypothalamus (LH) neuropeptides essential for stable consciousness: the orexins/hypocretins. Action potential-dependent orexin release inside and outside the hypothalamus evokes slow postsynaptic excitation. This excitation does not arise from modulation of classic neurotransmission, but involves direct action of orexins on their specific G-protein coupled receptors (GPCRs) coupled to ion channels. While millisecond-scale, GABA/glutamate connectivity within the LH may not be strong, re-assessing LH microcircuits from the peptidergic viewpoint is consistent with slow local microcircuits. The sustained actions of neuropeptides on neuronal membrane potential may enable core brain functions, such as temporal integration and the creation of lasting permissive signals that act as “eligibility traces” for context-dependent information routing and plasticity. The slowness of neuropeptides has unique advantages for efficient neuronal processing and feedback control of consciousness.

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Rapid sensory integration in orexin neurons governs probability of future movements

Cited by 2 publications

References 43 publications

Optogenetic and pharmacological interventions link hypocretin neurons to impulsivity in mice

Optogenetic and pharmacological interventions link hypocretin neurons to impulsivity in mice

Neuropeptides as Primary Mediators of Brain Circuit Connectivity

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