The interaction between cortisol and testosterone predicts leadership within rock hyrax social groups.

Group movement leadership is associated with higher risks for those in the front. Leaders are the first to explore new areas and may be exposed to predation. Individual differences in risk-taking behavior may be related to hormonal differences. In challenging circumstances, such as risk-taking leadership that may pose a cost to the leader, cortisol is secreted both to increase the likelihood of survival by restoring homeostasis, and to mediate cooperative behavior. Testosterone too has a well-established role in risk-taking behavior, and the dual-hormone hypothesis posits that the interaction of testosterone and cortisol can predict social behavior. Based on the dual-hormone hypothesis, we investigated here whether the interaction between testosterone and cortisol can predict risk-taking leadership behavior in wild rock hyraxes (Procavia capensis). We used proximity loggers, observations, and playback trials to characterize hyrax leaders in three different leadership contexts that varied in their risk levels. In support of the dual-hormone hypothesis, we found that cortisol and testosterone interactions predict leadership that involves risk. Across different circumstances that involved low or high levels of risk, testosterone was positively related to leadership, but only in individuals (both males and females) with low levels of cortisol. We also found an interaction between these hormone levels and age at the low-risk scenarios. We suggest that the close social interactions and affiliative behavior among hyrax females within small egalitarian groups may make female leadership less risky, and therefore less stressful, and allow female leaders to influence group activities.

High-resolution tracking of hyrax social interactions highlights nighttime drivers of animal sociality.

Network structure is a key driver of animal fitness, pathogen transmission, information spread, and population demographics in the wild. Although a considerable body of research applied network analysis to animal societies, only little effort has been devoted to separate daytime and nighttime sociality and explicitly test working hypotheses on social structures emerging at night. Here, we investigated the nighttime sociality of a wild population of rock hyraxes (Procavia capensis) and its relation to daytime social structure. We recorded nearly 15,000 encounters over 27 consecutive days and nights using proximity loggers. Overall, we show that hyraxes are more selective of their social affiliates at night compared to daytime. We also show that hyraxes maintain their overall network topology while reallocating the weights of social relationships at the daily and monthly scales, which could help hyraxes maintain their social structure over long periods while adapting to local constraints and generate complex social dynamics. These results suggest that complex network dynamics can be a by-product of simple daily social tactics and do not require high cognitive abilities. Our work sheds light on the function of nighttime social interactions in diurnal social species.

Sex-associated and context-dependent leadership in the rock hyrax.

In many mammalian species, both sexes may take leadership role, but different traits may play a role in determining variation within species. Here we examine the effect of sex on leadership. We present three complementary datasets derived from a well-studied population of wild rock hyrax (Procavia capensis). The findings demonstrated that male and female rock hyraxes take on different leadership positions, depending on the context. When risk is moderate, more likely to lead are younger resident males, which experience high cortisol and lower testosterone levels. However, during acute predation scenarios, more likely to lead are males with lower centrality status. We suggest that hyrax males exhibit risky behaviors that may reflect their need for self-advertisement. In contrast, leadership among group females is more equally distributed. Females have little to gain from risky actions due to the lack of competition among them, but nonetheless take leadership positions.

The "Law of Brevity" in animal communication: Sex-specific signaling optimization is determined by call amplitude rather than duration.

The efficiency of informational transfer is one of the key aspects of any communication system. The informational coding economy of human languages is often demonstrated by their almost universal fit to Zipf's "Law of Brevity," expressing negative relationship between word length and its usage frequency. Animal vocal systems, however, provided mixed results in their adherence to this relationship, potentially due to conflicting evolutionary pressures related to differences in signaling range and communicational needs. To examine this potential parallel between human and animal vocal communication, and also to explore how divergent, sex-specific, communicational settings affect signaling efficiency within a species, we examined the complete vocal repertoire of rock hyraxes (Procavia capensis). As male and female hyraxes differ in their sociality levels and male hyraxes vocal repertoire is dominated by sexual advertisement songs, we hypothesized that sex-specific vocal repertoires could be subjected to different signaling optimization pressures. Our results show that the sexes differ in repertoire size, call usage, and adherence to coding efficiency principles. Interestingly, the classic call length/call usage relationship is not consistently found in rock hyraxes. Rather, a negative relationship between call amplitude and call usage is found, suggesting that the efficiency of the vocal repertoire is driven by call amplitude rather than duration. We hypothesize that, in contrast to human speech that is mainly intended for short distance, the need for frequent long-range signaling shapes an animal's vocal repertoire efficiency according to the cost of call amplitude rather than call length. However, call duration may be a secondary factor affecting signaling efficiency, in cases where amplitude is under specific selection pressures, such as sexual selection.

The Claustrum Supports Resilience to Distraction.

A barrage of information constantly assaults our senses, of which only a fraction is relevant at any given point in time. However, the neural circuitry supporting the suppression of irrelevant sensory distractors is not completely understood. The claustrum, a circuit hub with vast cortical connectivity, is an intriguing brain structure, whose restrictive anatomy, thin and elongated, has precluded functional investigation. Here, we describe the use of Egr2-CRE mice to access genetically defined claustral neurons. Utilizing conditional viruses for anterograde axonal labeling and retrograde trans-synaptic tracing, we validated this transgenic model for accessing the claustrum and extended the known repertoire of claustral input/output connectivity. Addressing the function of the claustrum, we inactivated CLEgr2+ neurons, chronically as well as acutely, in mice performing an automated two-alternative forced-choice behavioral task. Strikingly, inhibition of CLEgr2+ neurons did not significantly impact task performance under varying delay times and cue durations, but revealed a selective role for the claustrum in supporting performance in the presence of an irrelevant auditory distractor. Further investigation of behavior, in the naturalistic maternal pup-retrieval task, replicated the result of sensitization to an auditory distractor following inhibition of CLEgr2+ neurons. Initiating investigation into the underlying mechanism, we found that activation of CLEgr2+ neurons modulated cortical sensory processing, suppressing tone representation in the auditory cortex. This functional study, utilizing selective genetic access, implicates the claustrum in supporting resilience to distraction, a fundamental aspect of attention.

Attention: the claustrum.

The claustrum is a mysterious thin sheet of neurons lying between the insular cortex and the striatum. It is reciprocally connected with almost all cortical areas, including motor, somatosensory, visual, auditory, limbic, associative, and prefrontal cortices. In addition, it receives neuromodulatory input from subcortical structures. A decade ago, Sir Francis Crick and Christof Koch published an influential review proposing the claustrum as the 'seat of consciousness', spurring a revival of interest in the claustrum. We review the literature on the claustrum, emphasizing recent discoveries, and develop a detailed hypothesis describing a role for the claustrum in the segregation of attention.

Acetylcholinesterase loosens the brain's cholinergic anti-inflammatory response and promotes epileptogenesis.

Recent studies show a key role of brain inflammation in epilepsy. However, the mechanisms controlling brain immune response are only partly understood. In the periphery, acetylcholine (ACh) release by the vagus nerve restrains inflammation by inhibiting the activation of leukocytes. Recent reports suggested a similar anti-inflammatory effect for ACh in the brain. Since brain cholinergic dysfunctions are documented in epileptic animals, we explored changes in brain cholinergic gene expression and associated immune response during pilocarpine-induced epileptogenesis. Levels of acetylcholinesterase (AChE) and inflammatory markers were measured using real-time RT-PCR, in-situ hybridization and immunostaining in wild type (WT) and transgenic mice over-expressing the "synaptic" splice variant AChE-S (TgS). One month following pilocarpine, mice were video-monitored for spontaneous seizures. To test directly the effect of ACh on the brain's innate immune response, cytokines expression levels were measured in acute brain slices treated with cholinergic agents. We report a robust up-regulation of AChE as early as 48 h following pilocarpine-induced status epilepticus (SE). AChE was expressed in hippocampal neurons, microglia, and endothelial cells but rarely in astrocytes. TgS mice overexpressing AChE showed constitutive increased microglial activation, elevated levels of pro-inflammatory cytokines 48 h after SE and accelerated epileptogenesis compared to their WT counterparts. Finally we show a direct, muscarine-receptor dependant, nicotine-receptor independent anti-inflammatory effect of ACh in brain slices maintained ex vivo. Our work demonstrates for the first time, that ACh directly suppresses brain innate immune response and that AChE up-regulation after SE is associated with enhanced immune response, facilitating the epileptogenic process. Our results highlight the cholinergic system as a potential new target for the prevention of seizures and epilepsy.

Cholinergic-associated loss of hnRNP-A/B in Alzheimer's disease impairs cortical splicing and cognitive function in mice.

Genetic studies link inherited errors in RNA metabolism to familial neurodegenerative disease. Here, we report such errors and the underlying mechanism in sporadic Alzheimer's disease (AD). AD entorhinal cortices presented globally impaired exon exclusions and selective loss of the hnRNP A/B splicing factors. Supporting functional relevance, hnRNP A/B knockdown induced alternative splicing impairments and dendrite loss in primary neurons, and memory and electrocorticographic impairments in mice. Transgenic mice with disease-associated mutations in APP or Tau displayed no alterations in hnRNP A/B suggesting that its loss in AD is independent of Aß and Tau toxicity. However, cholinergic excitation increased hnRNP A/B levels while in vivo neurotoxin-mediated destruction of cholinergic neurons caused cortical AD-like decrease in hnRNP A/B and recapitulated the alternative splicing pattern of AD patients. Our findings present cholinergic-mediated hnRNP A/B loss and impaired RNA metabolism as important mechanisms involved in AD.

Deep brain stimulation induces rapidly reversible transcript changes in Parkinson's leucocytes.

Subthalamic deep brain stimulation (DBS) reversibly modulates Parkinson's disease (PD) motor symptoms, providing an unusual opportunity to compare leucocyte transcripts in the same individuals before and after neurosurgery and 1 hr after stimulus cessation (ON- and OFF-stimulus). Here, we report DBS-induced reversibility and OFF-stimulus restoration in 12 of 16 molecular functions and 3 of 4 biological processes shown in exon microarrays to be differentially expressed between PD patients and controls, post-DBS from pre-DBS and OFF from ON states. Intriguingly, 6 of 18 inflammation and immune-related functions exhibited reversibility, and the extent of stimulus-induced changes correlated with the neurological DBS efficacy, suggesting mechanistic implications. A minimal list of 29 transcripts that changed in all three comparisons between states discriminated pre-surgery and OFF states from post-surgery and controls. Six of these transcripts were found to be able to distinguish between PD patients and both healthy controls and patients with other neurological diseases in a previously published whole blood 3' array data study of early PD patients. Our findings support the future use of this approach for identifying targets for therapeutic intervention and assessing the efficacy of current and new treatments in this and other neurological diseases.