Enhancing scientific dissemination in neuroscience via preprint peer-review: "Peer Community In Circuit Neuroscience"

The dissemination of scientific results and new technologies in biomedical science is rapidly evolving from an exclusive and fee-oriented publishing system towards more open, free and independent strategies for sharing knowledge. In this context, preprint servers such as bioRxiv answer a very real scientific need by enabling the rapid, free and easy dissemination of findings, regardless of whether these are novel, replicated, or even showcasing negative results. Currently, thousands of manuscripts are being shared via bioRxiv each month, and neuroscience is the largest and fastest growing subject category. However, commenting on bioRxiv is declining and no structured scientific validation such as peer-review is currently available. The Peer Community In (PCI) platform addresses this unmet need by facilitating the rigorous evaluation and validation of preprints, and PCI Circuit Neuroscience (PCI C Neuro) aims to develop and extend this tool for the neuroscience community. Here we discuss PCI C Neuro's mission, how it works, and why it is an essential initiative in this new era of open science

Role of spontaneous and sensory orexin network dynamics in rapid locomotion initiation.

Appropriate motor control is critical for normal life, and requires hypothalamic hypocretin/orexin neurons (HONs). HONs are slowly regulated by nutrients, but also display rapid (subsecond) activity fluctuations in vivo. The necessity of these activity bursts for sensorimotor control and their roles in specific phases of movement are unknown. Here we show that temporally-restricted optosilencing of spontaneous or sensory-evoked HON bursts disrupts locomotion initiation, but does not affect ongoing locomotion. Conversely, HON optostimulation initiates locomotion with subsecond delays in a frequency-dependent manner. Using 2-photon volumetric imaging of activity of >300 HONs during sensory stimulation and self-initiated locomotion, we identify several locomotion-related HON subtypes, which distinctly predict the probability of imminent locomotion initiation, display distinct sensory responses, and are differentially modulated by food deprivation. By causally linking HON bursts to locomotion initiation, these findings reveal the sensorimotor importance of rapid spontaneous and evoked fluctuations in HON ensemble activity

Orexin neurons track temporal features of blood glucose in behaving mice

Does the brain track how fast our blood glucose is changing? Knowing such a rate of change would enable the prediction of an upcoming state and a timelier response to this new state. Hypothalamic arousal-orchestrating hypocretin/orexin neurons (HONs) have been proposed to be glucose sensors, yet whether they track glucose concentration (proportional tracking) or rate of change (derivative tracking) is unknown. Using simultaneous recordings of HONs and blood glucose in behaving male mice, we found that maximal HON responses occur in considerable temporal anticipation (minutes) of glucose peaks due to derivative tracking. Analysis of >900 individual HONs revealed glucose tracking in most HONs (98%), with derivative and proportional trackers working in parallel, and many (65%) HONs multiplexed glucose and locomotion information. Finally, we found that HON activity is important for glucose-evoked locomotor suppression. These findings reveal a temporal dimension of brain glucose sensing and link neurobiological and algorithmic views of blood glucose perception in the brain's arousal orchestrators

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Supplementary data for bioRxiv preprint Hartmann et al. 202

Ultra-sparse Connectivity within the Lateral Hypothalamus

The lateral hypothalamic area (LH) is a vital controller of arousal, feeding, and metabolism [1, 2], which integrates external and internal sensory information. Whereas sensory and whole-body output properties of LH cell populations have received much interest, their intrinsic synaptic organization has remained largely unstudied. Local inhibitory and excitatory connections could help integrate and filter sensory information and mutually inhibitory connections [3] could allow coordinating activity between LH cell types, some of which have mutually exclusive behavioral effects, such as LH VGLUT2 and VGAT neurons [4, 5, 6, 7] and orexin- (ORX) and melanin-concentrating hormone (MCH) neurons [8, 9, 10]. However, classical Golgi staining studies did not find interneurons with locally ramifying axons in the LH [11, 12], and nearby subthalamic and thalamic areas lack local synaptic connectivity [13, 14]. Studies with optogenetic circuit mapping within the LH have demonstrated only a minority of connections when a large pool of presynaptic neurons was activated [15, 16, 17, 18, 19]. Because multiple patch clamp has not been used to study LH connectivity, aside from a limited dataset of MCH neurons where no connections were discovered [15], we used quadruple whole-cell recordings to screen connectivity within the LH with standard methodology we previously used in the neocortex [20, 21, 22]. Finding a lack of local connectivity, we used optogenetic circuit mapping to study the strength of LH optogenetic responses and network oscillations, which were consistent with ultra-sparse intrinsic connectivity within the LH. These results suggest that input from other brain structures is decisive for selecting active populations in the LH.ISSN:0960-9822ISSN:1879-044

Orexin neuron activity in mating mice - a pilot study

Mating behaviours affect hypothalamic orexin/hypocretin neurons and vice versa. However, activity of orexin neurons has not been recorded during mating before. We report an anecdotal dataset of freely-moving miniature microscope recordings of orexin neuron activity during mating behaviours, as well as an oral sexual encounter previously undocumented in mice. Across the orexin neuron population in the male, firing rates were maximally diverse during ejaculation, similarly diverse though weaker during intromission, and inverse to this during anterior thrusting. In the female mouse, orexin neurons tended to decrease firing during intromission after a transient increase. We provide this brief dataset for re-use, to enable further studies of these rare behaviours with challenging surgical preparations

Multiple hypothalamic circuits sense and regulate glucose levels

The hypothalamus monitors body energy status in part through specialized glucose sensing neurons that comprise both glucose-excited and glucose-inhibited cells. Here we discuss recent work on the elucidation of neurochemical identities and physiological significance of these hypothalamic cells, including caveats resulting from the currently imprecise functional and molecular definitions of glucose sensing and differences in glucose-sensing responses obtained with different experimental techniques. We discuss the recently observed adaptive glucose-sensing responses of orexin/hypocretin-containing neurons, which allow these cells to sense changes in glucose levels rather than its absolute concentration, as well as the glucose-sensing abilities of melanin-concentrating hormone, neuropeptide Y, and proopiomelanocortin-containing neurons and the recent data on the role of ventromedial hypothalamic steroidogenic factor-1 (SF-1)/glutamate-containing cells in glucose homeostasis. We propose a model where orexin/hypocretin and SF-1/glutamate neurons cooperate in stimulating the sympathetic outflow to the liver and pancreas to increase blood glucose, which in turn provides negative feedback inhibition to these cells. Orexin/hypocretin neurons also stimulate feeding and reward seeking and are activated by hunger and stress, thereby providing a potential link between glucose sensing and goal-oriented behavior. The cell-type-specific neuromodulatory actions of glucose in several neurochemically distinct hypothalamic circuits are thus likely to be involved in coordinating higher brain function and behavior with autonomic adjustments in blood glucose levels

Cooperative Subnetworks of Molecularly Similar Interneurons in Mouse Neocortex

Summary Simultaneous co-activation of neocortical neurons is likely critical for brain computations ranging from perception and motor control to memory and cognition. While co-activation of excitatory principal cells (PCs) during ongoing activity has been extensively studied, that of inhibitory interneurons (INs) has received little attention. Here, we show in vivo and in vitro that members of two non-overlapping neocortical IN populations, expressing somatostatin (SOM) or vasoactive intestinal peptide (VIP), are active as populations rather than individually. We demonstrate a variety of synergistic mechanisms, involving population-specific local excitation, GABAergic disinhibition and excitation through electrical coupling, which likely underlie IN population co-activity. Firing of a few SOM or VIP INs recruits additional members within the cell type via GABAergic and cholinergic mechanisms, thereby amplifying the output of the population as a whole. Our data suggest that IN populations work as cooperative units, thus generating an amplifying nonlinearity in their circuit output